m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT02176
 [1], [2]
DNA methylation DNMT3A METTL3 Direct Inhibition m6A modification AKT1 AKT1 METTL3 Methylation : m6A sites
m6A Modification:
m6A Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
m6A Target RAC-alpha serine/threonine-protein kinase (AKT1)
 Targert Gene 
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type DNA methylation (DNAMeth)
Epigenetic Regulator Cysteine methyltransferase DNMT3A (DNMT3A) WRITER View Details
Regulated Target Methyltransferase-like protein 3 (METTL3) View Details
Crosstalk Relationship DNA methylation  →  m6A Inhibition
Crosstalk Mechanism DNA methylation directly impacts m6A modification through modulating the expression level of m6A regulator
Crosstalk Summary Methyltransferase-like 3 (METTL3) increased the pri-Let-7b, decreased both the pre-Let-7b and mature Let-7b, attenuating the Let-7b controlling of stem cell renewal. The addition of Metformin increased the bindings of DNA methyltransferase-3a/b (DNMT3A/DNMT3B) to the METTL3 promoter. With the help of the readers of NKAP and HNRNPA2B1, the cluster mediated m6A formation on pri-Let-7b processing increased the mature Let-7b, the key player in suppressing Notch signaling and re-captivating Osimertinib treatment. METTL3-mediated m6A methylation promotes lung cancer progression via activating PI3K/RAC-alpha serine/threonine-protein kinase (AKT1)/mTOR pathway.
Responsed Disease Lung cancer ICD-11: 2C25
 Disease Info 
Responsed Drug Osimertinib
 Drug Info 
Pathway Response mTOR signaling pathway hsa04150
PI3K-Akt signaling pathway hsa04151
In-vitro Model
 NCI-H1975 Lung adenocarcinoma Homo sapiens CVCL_1511
HCC827 Lung adenocarcinoma Homo sapiens CVCL_2063
In-vivo Model 5 × 106 A549 cells overexpressing METTL3 (Lv-METTL3) or control (Lv-Ctrl) were suspended in 100 uL phosphate-buffered saline (PBS), and were subcutaneously injected into mouse lower right flank. Drug treatment started in the Lv-METTL3 group when the tumour volume reached around 100 mm3. Mice were randomly divided into three groups to receive vehicle, GSK2536771 (30 mg/kg) or rapamycin (1 mg/kg). Drugs were administrated daily through intraperitoneal injection for 18 days. Treatment conditions were chosen as previously reported.
Full List of Potential Compound(s) Related to This m6A-centered Crosstalk
Cysteine methyltransferase DNMT3A (DNMT3A) 8 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name PMID27376512-Compound-Figure3CN Patented [3]
MOA Inhibitor
Activity EC50 = 1100 nM
External Link
CID: 117968550
TTD: D02VTV
 Compound Name PMID27376512-Compound-Figure3CG Patented [3]
MOA Inhibitor
Activity EC50 = 2400 nM
External Link
CID: 117967861
TTD: D03LZO
 Compound Name PMID27376512-Compound-Figure3CM Patented [3]
MOA Inhibitor
Activity EC50 = 1100 nM
External Link
CID: 117976053
TTD: D0F8AB
 Compound Name PMID27376512-Compound-Figure2aExample1 Patented [3]
MOA Inhibitor
Activity IC50 = 3000 nM
External Link
CID: 71521835
TTD: D01LUJ
 Compound Name PMID27376512-Compound-MTC-424 Patented [3]
MOA Inhibitor
Activity IC50 = 1940 nM
External Link
TTD: D02WRM
 Compound Name PMID27376512-Compound-MTC-427 Patented [3]
MOA Inhibitor
Activity IC50 = 295 nM
External Link
TTD: D0HA0J
 Compound Name PMID27376512-Compound-MTC-422 Patented [3]
MOA Inhibitor
Activity IC50 = 1430 nM
External Link
TTD: D0QY0N
 Compound Name PMID27376512-Compound-MTC-423 Patented [3]
MOA Inhibitor
Activity IC50 = 363 nM
External Link
TTD: D0W9VZ
RAC-alpha serine/threonine-protein kinase (AKT1) 40 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name Capivasertib Approved [4]
Synonyms
1143532-39-1; AZD-5363; capivasertib; AZD 5363; UNII-WFR23M21IE; WFR23M21IE; cc-638; 4-Amino-N-[(1s)-1-(4-Chlorophenyl)-3-Hydroxypropyl]-1-(7h-Pyrrolo[2,3-D]pyrimidin-4-Yl)piperidine-4-Carboxamide; C21H25ClN6O2; (S)-4-AMINO-N-(1-(4-CHLOROPHENYL)-3-HYDROXYPROPYL)-1-(7H-PYRROLO[2,3-D]PYRIMIDIN-4-YL)PIPERIDINE-4-CARBOXAMIDE; 4-Amino-N-[(1S)-1-(4-chlorophenyl)-3-hydroxypropyl]-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-4-piperidinecarboxamide; 4-Piperidinecarboxamide, 4-amino-N-[(1S)-1-(4-chlorophenyl)-3-hydroxypropyl]-1
    Click to Show/Hide
MOA Inhibitor
Activity IC50 = 3 nM
External Link
CID: 25227436
TTD: D01ZAQ
DrugBank: DB12218
 Compound Name GDC-0068 Phase 3 [5]
Synonyms
RG7440
    Click to Show/Hide
MOA Inhibitor
Activity IC50 = 157 nM
External Link
CID: 24788740
TTD: D0I4TH
DrugBank: DB11743
 Compound Name Enzastaurin Phase 3 [5]
Synonyms
LY317615; LE-0014; LY317615, Enzastaurin; 3-(1-methyl-1H-indol-3-yl)-4-{1-[1-(pyridin-2-ylmethyl)piperidin-4-yl]-1H-indol-3-yl}-1H-pyrrole-2,5-dione; 3-(1-methylindol-3-yl)-4-[1-[1-(pyridin-2-ylmethyl)piperidin-4-yl]indol-3-yl]pyrrole-2,5-dione
    Click to Show/Hide
MOA Inhibitor
External Link
CID: 176167
TTD: D0I6VU
DrugBank: DB06486
 Compound Name GSK2110183 Phase 2 [6]
MOA Modulator
External Link
CID: 46843057
TTD: D02NXM
DrugBank: DB11648
 Compound Name RX-0201 Phase 2 [7]
MOA Inhibitor
External Link
TTD: D07SYZ
 Compound Name Trametinib + 2141795 Phase 2 [6]
MOA Modulator
External Link
CID: 11707110
TTD: D0S5WP
DrugBank: DB08911
 Compound Name PTX-200 Phase 2 [5]
Synonyms
Plant-derived antiparkinsonian, Phytrix
    Click to Show/Hide
MOA Inhibitor
External Link
TTD: D0X7CV
 Compound Name CMX-2043 Phase 2 [8]
MOA Modulator
External Link
CID: 49802864
TTD: D01TBJ
DrugBank: DB12795
 Compound Name ARQ 092 Phase 2 [9]
Synonyms
Miransertib
    Click to Show/Hide
MOA Inhibitor
External Link
CID: 53262401
TTD: D07DWF
DrugBank: DB14982
 Compound Name CI-1033 Phase 2 [10]
Synonyms
Canertinib; Canertinib HCl; Canertinib dihydrochloride; Canertinib dihydrochloride [USAN]; CI1033; PD 183805; Canertinib dihydrochloride (USAN); PD-0183805; PD-183805; Canertinib, PD-183805, CI1033, PD183805; N-[4-(3-Chloro-4-fluorophenylamino)-7-(3-morpholin-4-ylpropoxy)quinazolin-6-yl]acrylamide dihydrochloride; N-[4-[(3-Chloro-4-fluorophenyl)amino]-7-[3-(4-morpholinyl)propoxy]-6-quinazolinyl]-2-propenamide dihydrochloride; N-[4-(3-chloro-4-fluoroanilino)-7-(3-morpholin-4-ylpropoxy)quinazolin-6-yl]prop-2-enamide; N-[4-(3-chloro-4-fluoroanilino)-7-(3-morpholin-4-ylpropoxy)quinazolin-6-yl]prop-2-enamide dihydrochloride; N-(4-(3-chloro-4-fluorophenyl)amino)-7-(3-morpholin-4-yl)propoxy)quinazolin-6-yl)prop-2-enamide dihydrochloride; N-{4-[(3-chloro-4-fluorophenyl)amino]-7-[3-(morpholin-4-yl)propoxy]quinazolin-6-yl}prop-2-enamide; N-(4-((3-Chloro-4-fluorophenyl)amino)-7-(3-(morpholin-4-yl)propoxy)quinazolin-6-yl)prop-2-enamide; 2-Propenamide, N-(4-((3-chloro-4-fluorophenyl) amino)-7-(3-(4-morpholinyl) propoxy)-6-quinazolinyl)-, dihydrochloride; 2-Propenamide, N-(4-((3-chloro-4-fluorophenyl)amino)-7-(3-(4-morpholinyl)propoxy)-6-quinazolinyl)-, dihydrochloride
    Click to Show/Hide
MOA Inhibitor
External Link
CID: 156414
TTD: D0YB3W
DrugBank: DB05424
 Compound Name Triciribine prodrug Phase 1/2 [6]
Synonyms
TSR-826; Triciribine prodrug (oral, cancer); Triciribine prodrug (oral, cancer), TSRL
    Click to Show/Hide
MOA Inhibitor
External Link
TTD: D09CCZ
 Compound Name BMS-754807 Phase 1 [11]
Synonyms
1001350-96-4; BMS 754807; BMS754807; UNII-W9E3353E8J; CHEMBL575448; CHEBI:88339; W9E3353E8J; 1-{4-[(3-cyclopropyl-1H-pyrazol-5-yl)amino]pyrrolo[2,1-f][1,2,4]triazin-2-yl}-N-(6-fluoropyridin-3-yl)-2-methyl-L-prolinamide; W-204348; J-501009; 2-Pyrrolidinecarboxamide, 1-[4-[(5-cyclopropyl-1H-pyrazol-3-yl)amino]pyrrolo[2,1-f][1,2,4]triazin-2-yl]-N-(6-fluoro-3-pyridinyl)-2-methyl-, (2S)-;2-Pyrrolidinecarboxamide, 1-[4-[(5-cyclopropyl-1H-pyrazol-3-yl)amino]pyrrolo[2,1-f][1,2,4]triazin-2-yl]-N-(6-fluoro-3-pyridin
    Click to Show/Hide
MOA Inhibitor
External Link
CID: 24785538
TTD: D02QWY
DrugBank: DB15399
 Compound Name ARQ 751 Phase 1 [5]
MOA Inhibitor
External Link
TTD: D0L8PZ
 Compound Name M2698 Phase 1 [5]
Synonyms
HXAUJHZZPCBFPN-QGZVFWFLSA-N; 1379545-95-5; SCHEMBL15262358; EX-A1187; AKOS030627134; M2698(MSC-2363318A)
    Click to Show/Hide
MOA Inhibitor
External Link
CID: 89808643
TTD: D06HYF
DrugBank: DB15431
 Compound Name PMID28460551-Compound-6 Patented [12]
MOA Inhibitor
External Link
TTD: D07QBF
 Compound Name Squalestatin 1 Terminated [13]
Synonyms
Zaragozic acid A; Squalestatin; 142561-96-4; ZARAGOZIC ACIDS A; UNII-1117HVX02L; CHEMBL280978; CHEBI:75170; 1117HVX02L; 1S-((4S-acetoxy-5R-methyl-3-methylene-6-phenylhexyl)-6-(E)-4S,6S-dimethyloct-2-enoyloxy)-4,7S-dihydroxy-2,8-dioxabicyclo[321]octane-3S,4S,5R-tricarboxylic acid; L-erythro-L-glycero-D-altro-7-Trideculo-7,4-furanosonic acid, 2,7-anhydro-3,4-di-C-carboxy-8,9,10,12,13-pentadeoxy-10-methylene-12-(phenylmethyl)-, 11-acetate 5-(4,6-dimethyl-2-octenoate), (5(2E,4S,6S),7S)-; Squalestatin 1, Glaxo; Zaragozic acid A, Glaxo
    Click to Show/Hide
MOA Inhibitor
External Link
CID: 6438355
TTD: D0O1AV
 Compound Name MYRIOCIN Investigative [13]
Synonyms
thermozymocidin; 35891-70-4; ISP-I; ISP-1; UNII-YRM4E8R9ST; (2S,3R,4R,6E)-2-Amino-3,4-dihydroxy-2-(hydroxymethyl)-14-oxo-6-eicosenoic acid; YRM4E8R9ST; Myriocin, Mycelia sterilia; Myriocin from Mycelia sterilia; CHEBI:582124; NCGC00163597-02; NCGC00163597-03; DSSTox_CID_26360; DSSTox_RID_81561; (2S,3R,4R,6E)-2-amino-3,4-dihydroxy-2-(hydroxymethyl)-14-oxoicos-6-enoic acid; DSSTox_GSID_46360; [2S,3R,4R]-(E)-2-Amino-3,4-dihydroxy-2-[hydroxymethyl]-14-oxo-6-eicosenoic Acid
    Click to Show/Hide
MOA Inhibitor
External Link
CID: 6438394
TTD: D07MQF
 Compound Name LD-101 Investigative [6]
Synonyms
AKT-SI-1
    Click to Show/Hide
MOA Inhibitor
External Link
CID: 24773090
TTD: D09DGE
 Compound Name A-674563 Investigative [14]
Synonyms
A 674563; A674563
    Click to Show/Hide
MOA Inhibitor
Activity Ki = 11 nM
External Link
CID: 11314340
TTD: D0CM6T
DrugBank: DB08568
 Compound Name Lactoquinomycin Investigative [15]
Synonyms
SCHEMBL12324296
    Click to Show/Hide
MOA Inhibitor
Activity IC50 = 149 nM
External Link
CID: 12967404
TTD: D0F8HX
 Compound Name VLI-27 Investigative [6]
Synonyms
AKT inhibitor (pancreatic cancer), NovaLead Pharma
    Click to Show/Hide
MOA Inhibitor
External Link
TTD: D0N7CY
 Compound Name A-443654 Investigative [16]
Synonyms
A-4436554
    Click to Show/Hide
MOA Inhibitor
Activity Ki = 0.16 nM
External Link
CID: 10172943
TTD: D0OX1T
DrugBank: DB08073
 Compound Name NU-1001-41 Investigative [6]
Synonyms
Anti-phospho-AKT monoclonal antibodies (cancer), Nuclea Biotechnologies
    Click to Show/Hide
External Link
TTD: D0PX5F
 Compound Name 4,5,6-trihydroxy-3-methylphthalide Investigative [17]
Synonyms
CHEMBL486813; AGUVVAYMPQDJDX-UHFFFAOYSA-; BDBM50242174; 3-methyl-4,5,6-trihydroxy-phthalide; 4,5,6-Trihydroxy-3-methylisobenzofuran-1(3H)-one
    Click to Show/Hide
MOA Inhibitor
Activity IC50 = 19700 nM
External Link
CID: 11424128
TTD: D0RZ1H
 Compound Name ALM-301 Investigative [6]
Synonyms
Akt inhibitors (cancer), Almac
    Click to Show/Hide
MOA Inhibitor
External Link
TTD: D0V1ES
 Compound Name BX-517 Investigative [18]
Synonyms
BX517; 850717-64-5; UNII-SYV8VN8W5K; SYV8VN8W5K; pdk-1 inhibitors; BX517(PDK1 inhibitor2); Indolinone based inhibitor, 4i; SCHEMBL5567818; CHEMBL228654; 5-Ureido-3-(1-(pyrrol-2-yl)ethylidene)indolin-2-one; BDBM17004; MolPort-046-033-615; BCP16225; EX-A2243; ZINC14962724; AKOS032945106; CS-6066; Urea, N-(2,3-dihydro-2-oxo-3-((3Z)-1-(1H-pyrrol-2-yl)ethylidene)-1H-indol-5-yl)-; Urea, N-(2,3-dihydro-2-oxo-3-(1-(1H-pyrrol-2-yl)ethylidene)-1H-indol-5-yl)-; Urea, (2,3-dihydro-2-oxo-3-(1-(1H-pyrrol-2-yl)ethylidene)-1H-indol-5-
    Click to Show/Hide
MOA Inhibitor
External Link
CID: 11161844
TTD: D0L5AB
 Compound Name Inositol 1,3,4,5-Tetrakisphosphate Investigative [19]
Synonyms
Inositol-1,3,4,5-tetraphosphate; Ins-1,3,4,5-P4; 1D-myo-inositol 1,3,4,5-tetrakisphosphate; Inositol-1,3,4,5-tetrakisphosphate; inositol-(1,3,4,5)-tetrakisphosphate; Inositol 1,3,4,5-tetraphosphate; myo-Inositol-1,3,4,5-tetrakisphosphate; CHEMBL23552; D-myo-inositol 1,3,4,5-tetrakisphosphate; CHEBI:16783; myo-Inositol, 1,3,4,5-tetrakis(dihydrogen phosphate); 1D-myo-inositol 1,3,4,5-tetrakis(dihydrogen phosphate); Ins(1,3,4,5)P4; 1bwn; 4IP; 102850-29-3; myo-Inositol 1,3,4,5-tetraphosphate
    Click to Show/Hide
MOA Inhibitor
External Link
CID: 107758
TTD: D0MH9X
DrugBank: DB01863
 Compound Name (Z)-3-((1H-pyrrol-2-yl)methylene)indolin-2-one Investigative [18]
Synonyms
oxindole i; CHEMBL86755; 3-(1H-Pyrrol-2-ylmethylene)-1,3-dihydroindol-2-one; oxindole 1; AC1NZGXV; K00027; Indolinone based inhibitor, 1; SCHEMBL1162655; SCHEMBL13819612; BDBM17015; MolPort-023-197-743; SEZFNTZQMWJIAI-FLIBITNWSA-N; ZINC3874586; HSCI1_000049; NCGC00343760-01; BRD-K51816706-001-01-7; (3Z)-3-(1H-pyrrol-2-ylmethylidene)-1H-indol-2-one; 3-[(1H-Pyrrole-2-yl)methylene]-1H-indole-2(3H)-one; Z-(1H-Pyrrol-2-ylmethylene)-1,3-dihydro-indol-2-one
    Click to Show/Hide
MOA Inhibitor
Activity IC50 = 2300 nM
External Link
CID: 5908088
TTD: D00ATA
 Compound Name Akt inhibitor VIII Investigative [20]
Synonyms
isozyme-selective, Akti-1/2
    Click to Show/Hide
MOA Inhibitor
Activity IC50 = 58 nM
External Link
CID: 135398501
TTD: D05APZ
 Compound Name SB-747651A Investigative [21]
Synonyms
CHEMBL188434; compound 26; SCHEMBL4719834; GTPL8130; BDBM24996; oxadiazole-containing compound, 9; MBCJUIJWPYUEBX-UHFFFAOYSA-N; ZINC13998530; NCGC00273984-05; NCGC00273984-03; SB-747651; 4-{1-ethyl-7-[(piperidin-4-ylamino)methyl]-1H-imidazo[4,5-c]pyridin-2-yl}-1,2,5-oxadiazol-3-amine; [2-(4-Amino-furazan-3-yl)-1-ethyl-1H-imidazo[4,5-c]pyridin-7-ylmethyl]-piperidin-4-yl-amine
    Click to Show/Hide
MOA Inhibitor
Activity IC50 = 200 nM
External Link
CID: 11393719
TTD: D0I1FJ
 Compound Name PMID20005102C1 Investigative [22]
Synonyms
GTPL8181; BDBM50305878; B99
    Click to Show/Hide
MOA Inhibitor
Activity IC50 = 1 nM
External Link
CID: 46225540
TTD: D0L2WP
 Compound Name STAUROSPORINONE Investigative [23]
MOA Inhibitor
External Link
TTD: D0GB4V
 Compound Name Ro31-8220 Investigative [23]
Synonyms
Bisindolylmaleimide IX; ro 31-8220; 125314-64-9; Ro 31 8220; Ro 318220; UNII-W9A0B5E78O; Ro-318220; Ro-31-8220; CHEMBL6291; W9A0B5E78O; CHEBI:38912; 3-{3-[4-(1-methyl-1H-indol-3-yl)-2,5-dioxo-2,5-dihydro-1H-pyrrol-3-yl]-1H-indol-1-yl}propyl carbamimidothioate; 3-{3-[4-(1-methyl-1H-indol-3-yl)-2,5-dioxo-2,5-dihydro-1H-pyrrol-3-yl]-1H-indol-1-yl}propyl imidothiocarbamate; CHEMBL1591531; Carbamimidothioic acid, 3-(3-(2,5-dihydro-4-(1-methyl-1H-indol-3-yl)-2,5-dioxo-1H-pyrrol-3-yl)-1H-indol-1-yl)propyl; bisindolymaleimide IX
    Click to Show/Hide
MOA Inhibitor
External Link
CID: 5083
TTD: D0M5FF
 Compound Name BMS-536924 Investigative [24]
MOA Inhibitor
External Link
CID: 135440466
TTD: D0M4SY
 Compound Name KN-62 Investigative [23]
Synonyms
KN-62 (non-isomeric); GTPL6001; HMS3229A04; CCG-206863
    Click to Show/Hide
MOA Inhibitor
External Link
CID: 5312126
TTD: D0N6ES
 Compound Name CI-1040 Investigative [23]
MOA Inhibitor
External Link
CID: 6918454
TTD: D0B9BU
DrugBank: DB12429
 Compound Name 4,5,6,7-tetrabromo-1H-benzo[d][1,2,3]triazole Investigative [25]
Synonyms
4,5,6,7-tetrabromobenzotriazole
    Click to Show/Hide
MOA Inhibitor
External Link
CID: 1694
TTD: D0O1YH
DrugBank: DB04462
 Compound Name 4-[(3,5-diamino-1H-pyrazol-4-yl)diazenyl]phenol Investigative [26]
MOA Inhibitor
External Link
CID: 9859248
TTD: D0A5RM
 Compound Name Bisindolylmaleimide-I Investigative [23]
Synonyms
Bisindolylmaleimide i; 133052-90-1; GF 109203X; GF109203X; Go 6850; GF-109203X; RBT205 INHIBITOR; Go-6850; UNII-L79H6N0V6C; Bisindolylmaleimide I (GF 109203X); CHEMBL7463; 3-{1-[3-(DIMETHYLAMINO)PROPYL]-1H-INDOL-3-YL}-4-(1H-INDOL-3-YL)-1H-PYRROLE-2,5-DIONE; 3-(1-(3-(Dimethylamino)propyl)-1H-indol-3-yl)-4-(1H-indol-3-yl)-1H-pyrrole-2,5-dione; L79H6N0V6C; QMGUOJYZJKLOLH-UHFFFAOYSA-N; 2-[1-(3-dimethylaminopropyl)indol-3-yl]-3-(indol-3-yl)maleimide; GF-109203; Go6850
    Click to Show/Hide
MOA Inhibitor
External Link
CID: 2396
TTD: D0TO6S
DrugBank: DB03777
 Compound Name RO-316233 Investigative [23]
Synonyms
119139-23-0; bisindolylmaleimide iv; 3,4-di(1H-indol-3-yl)-1H-pyrrole-2,5-dione; Arcyriarubin A; 3,4-Bis(3-indolyl)maleimide; 3,4-Di-1H-indol-3-yl-1H-pyrrole-2,5-dione; UNII-MBK3OO5K8T; BIM IV; 3,4-bis(1H-indol-3-yl)pyrrole-2,5-dione; MBK3OO5K8T; CHEMBL266487; 3,4-bis(1H-indol-3-yl)-2,5-dihydro-1H-pyrrole-2,5-dione; DQYBRTASHMYDJG-UHFFFAOYSA-N; 2,3-bis(1H-Indol-3-yl)maleimide; 1H-Pyrrole-2,5-dione, 3,4-di-1H-indol-3-yl-; Ro-31-6233; AK-15401; 3,4-bis(3-indolyl)-1H-pyrrole-2,5-dione; Bisindoylmaleimide; Bisindolyl deriv. 3
    Click to Show/Hide
MOA Inhibitor
External Link
CID: 2399
TTD: D0L8HO
2C25: Lung cancer 52 Compound(s) Regulating the Disease Click to Show/Hide the Full List
 Compound Name Adagrasib Approved [27]
Synonyms
2326521-71-3; MRTX-849; UNII-8EOO6HQF8Y; 8EOO6HQF8Y; 2-((S)-4-(7-(8-Chloronaphthalen-1-yl)-2-(((S)-1-methylpyrrolidin-2-yl)methoxy)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-4-yl)-1-(2-fluoroacryloyl)piperazin-2-yl)acetonitrile; CHEMBL4594350; SCHEMBL20974691; GTPL10888; Kras G12C inhibitor MRTX849; BCP31538; EX-A3258; MRTX 849; MFCD32263433; s8884; compound 20 [PMID: 32250617]; BS-16211; HY-130149; CS-0105265; 2-Piperazineacetonitrile, 4-(7-(8-chloro-1-naphthalenyl)-5,6,7,8-tetrahydro-2-(((2S)-1-methyl-2-pyrrolidinyl)methoxy)pyrido(3,4-d)pyrimidin-4-yl)-1-(2-fluoro-1-oxo-2-propen-1-yl)-, (2S)-
    Click to Show/Hide
External Link
CID: 138611145
TTD: DUQV41
 Compound Name Amivantamab Approved [28]
External Link
TTD: DQ5X1Z
 Compound Name Mobocertinib Approved [29]
Synonyms
1847461-43-1; TAK-788; TAK788; AP32788; UNII-39HBQ4A67L; 39HBQ4A67L; propan-2-yl 2-[4-{[2-(dimethylamino)ethyl](methyl)amino}-2-methoxy-5-(prop-2-enamido)anilino]-4-(1-methyl-1H-indol-3-yl)pyrimidine-5-carboxylate; Mobocertinib [INN]; Mobocertinib [USAN]; AP-32788; Mobocertinib (TAK788); Mobocertinib(TAK-788); SCHEMBL17373133; GTPL10468; BDBM368374; BCP31045; EX-A3392; US10227342, Example 10; MFCD32669806; NSC825519; s6813; TAK-788;AP32788; WHO 11183; NSC-825519; example 94 [WO2015195228A1]; HY-135815; CS-0114256; TAK-788;TAK 788; AP 32788; 5-Pyrimidinecarboxylic acid, 2-((4-((2-(dimethylamino)ethyl)methylamino)-2-methoxy-5-((1-oxo-2-propen-1-yl)amino)phenyl)amino)-4-(1-methyl-1H-indol-3-yl)-, 1-methylethyl ester; C(C=C)(=O)NC=1C(=CC(=C(C=1)NC1=NC=C(C(=N1)C1=CN(C2=CC=CC=C12)C)C(=O)OC(C)C)OC)N(C)CCN(C)C; Isopropyl 2-((5-acrylamido-4-((2-(dimethylamino)ethyl)(methyl)amino)-2-methoxyphenyl)amino)-4-(1-methyl-1H-indol-3-yl)pyrimidine-5-carboxylate; Isopropyl 2-(5-acrylamido-4-((2-(dimethylamino)ethyl)(methyl)amino)-2-methoxyphenylamino)-4-(1-methyl-1H-indol-3-yl)pyrimidine-5-carboxylate; Propan-2-yl 2-(5-(acryloylamino)-4-((2-(dimethylamino)ethyl)(methyl)amino)-2-methoxyanilino)-4-(1-methyl-1H-indol-3-yl)pyrimidine-5-carboxylate; propan-2-yl 2-[4-[2-(dimethylamino)ethyl-methylamino]-2-methoxy-5-(prop-2-enoylamino)anilino]-4-(1-methylindol-3-yl)pyrimidine-5-carboxylate
    Click to Show/Hide
External Link
CID: 118607832
TTD: DI4HA7
 Compound Name Sugemalimab Approved in China [30]
External Link
TTD: DDZ48Y
 Compound Name Sacituzumab govitecan Approved [31]
Synonyms
1491917-83-9; 1535963-91-7; 1796566-95-4; CYSTEINYL CL2A-SN-38; DA64T2C2IO; DTXSID401335985; EX-A4354; F82944; GOVITECAN CYSTEINYL CONJUGATE; hRS 7SN38; hRS7-SN38; IMMU 132; IMMU-132; M9BYU8XDQ6; Sacituzumab govitecan; Sacituzumab govitecan [USAN]; sacituzumab-govitecan; Satralizumab linker; SN-38 CYSTEINYL CONJUGATE; UNII-M9BYU8XDQ6
    Click to Show/Hide
External Link
CID: 91668186
TTD: D8LAE2
 Compound Name Atezolizumab Approved [32]
External Link
TTD: D0YM2K
 Compound Name Tepotinib Approved [33]
Synonyms
1100598-32-0; EMD 1214063; UNII-1IJV77EI07; Tepotinib (EMD 1214063); EMD1214063; 1IJV77EI07; MSC-2156119J; Benzonitrile, 3-[1,6-dihydro-1-[[3-[5-[(1-methyl-4-piperidinyl)methoxy]-2-pyrimidinyl]phenyl]methyl]-6-oxo-3-pyridazinyl]-; C29H28N6O2; Tepotinib [INN]; Benzonitrile, 3-[1,6-Dihydro-1-[[3-[5-[(1-Methyl-4-Piperidinyl)Methoxy]-2-PyriMidinyl]Phenyl]Methyl]-6-Oxo-3-Pyridazinyl]; Benzonitrile, 3-(1,6-dihydro-1-((3-(5-((1-methyl-4-piperidinyl)methoxy)-2-pyrimidinyl)phenyl)methyl)-6-oxo
    Click to Show/Hide
External Link
CID: 25171648
TTD: D0R8QG
DrugBank: DB15133
 Compound Name Sotorasib Approved [34]
Synonyms
AMG-510; AMG510; AMG-510 racemate; 2252403-56-6; AMG 510; Kras G12C inhibitor 9; 2296729-00-3; UNII-2B2VM6UC8G; 2B2VM6UC8G; CHEMBL4535757; 2296729-00-3 (racemate); 4-((S)-4-Acryloyl-2-methylpiperazin-1-yl)-6-fluoro-7-(2-fluoro-6-hydroxyphenyl)-1-(2-isopropyl-4-methylpyridin-3-yl)pyrido[2,3-d]pyrimidin-2(1H)-one; 6-fluoro-7-(2-fluoro-6-hydroxyphenyl)-1-(4-methyl-2-propan-2-ylpyridin-3-yl)-4-[(2S)-2-methyl-4-prop-2-enoylpiperazin-1-yl]pyrido[2,3-d]pyrimidin-2-one; Sotorasib [INN]; 6-Fluoro-7-(2-fluoro-6-hydroxyphenyl)-1-(4-methyl-2-propan-2-ylpyridin-3-yl)-4-((2S)-2-methyl-4-prop-2-enoylpiperazin-1-yl)pyrido(2,3-d)pyrimidin-2-one; AMG510 racemate; Sotorasib [USAN]; AMG-510(racemate); Kras mutant-targeting AMG 510; SCHEMBL20560375; GTPL10678; AMG 510 pound>>AMG-510; AMY16918; BCP30452; BCP33368; EX-A3538; BDBM50514402; NSC818433; s8830; WHO 11370; DB15569; NSC-818433; BS-16684; HY-114277; CS-0081316; compound (R)-38 [PMID: 31820981]; (1m)-6-Fluoro-7-(2-fluoro-6-hydroxyphenyl)-1-(4-methyl-2-(propan-2-yl)pyridin-3-yl)-4-((2S)-2-methyl-4-(prop-2-enoyl)piperazin-1-yl)pyrido(2,3-d)pyrimidin-2(1H)-one; (1S)-4-((S)-4-Acryloyl-2-methylpiperazin-1-yl)-6-fluoro-7-(2-fluoro-6-hydroxyphenyl)-1-(2-isopropyl-4-methylpyridin-3-yl)pyrido[2,3-d]pyrimidin-2(1H)-one; 2296729-66-1; Pyrido(2,3-d)pyrimidin-2(1H)-one, 6-fluoro-7-(2-fluoro-6-hydroxyphenyl)-1-(4-methyl-2-(1-methylethyl)-3-pyridinyl)-4-((2S)-2-methyl-4-(1-oxo-2-propen-1-yl)-1-piperazinyl)-
    Click to Show/Hide
External Link
CID: 137278711
TTD: D0R7LD
DrugBank: DB15569
 Compound Name Entrectinib Approved [35]
Synonyms
1108743-60-7; RXDX-101; UNII-L5ORF0AN1I; Entrectinib (RXDX-101); L5ORF0AN1I; Benzamide, N-[5-[(3,5-difluorophenyl)methyl]-1H-indazol-3-yl]-4-(4-methyl-1-piperazinyl)-2-[(tetrahydro-2H-pyran-4-yl)amino]-; Benzamide, N-(5-((3,5-difluorophenyl)methyl)-1H-indazol-3-yl)-4-(4-methyl-1-piperazinyl)-2-((tetrahydro-2H-pyran-4-yl)amino)-; Entrectinib [USAN:INN]; YMX; Kinome_2659; Entrectinib(rxdx-101); Entrectinib (USAN/INN); SCHEMBL3512601; GTPL8290; CHEMBL1983268; KS-00000TSK
    Click to Show/Hide
External Link
CID: 25141092
TTD: D0O0LS
DrugBank: DB11986
 Compound Name Repotrectinib Approved [36]
Synonyms
FIKPXCOQUIZNHB-RRKGBCIJSA-N; SCHEMBL20438940; TPX 0005; BCP19778
    Click to Show/Hide
External Link
CID: 135565923
TTD: D05NFR
 Compound Name MYL-1402O Phase 3 [37]
Synonyms
bevacizumab biosimilar
    Click to Show/Hide
External Link
TTD: DYH3Q6
 Compound Name AB154 Phase 3 [38]
Synonyms
Domvanalimab
    Click to Show/Hide
External Link
TTD: DT1FS0
 Compound Name Datopotamab deruxtecan Phase 3 [39]
External Link
TTD: DP41HV
 Compound Name CS1001 Phase 3 [40]
External Link
TTD: D3MP1S
 Compound Name JDQ443 Phase 3 [41]
Synonyms
(S)-JDQ-443; 1-(6-((4S)-4-(5-Chloro-6-methyl-1H-indazol-4-yl)-5-methyl-3-(1-methyl-1H-indazol-5-yl)-1H-pyrazol-1-yl)-2-azaspiro[3.3]heptan-2-yl)prop-2-en-1-one; 1-[6-[(4R)-4-(5-chloro-6-methyl-1H-indazol-4-yl)-5-methyl-3-(1-methyl-1H-inda zol-5-yl)-1H-pyrazol-1-yl]-2-azaspiro[3.3]hept-2-yl]- 2-Propen-1-one; 1-[6-[(4R)-4-(5-Chloro-6-methyl-1H-indazol-4-yl)-5-methyl-3-(1-methyl-1H-indazol-5-yl)-1H-pyrazol-1-yl]-2-azaspiro[3.3]hept-2-yl]-2-propen-1-one; 1-[6-[4-(5-chloro-6-methyl-1H-indazol-4-yl)-5-methyl-3-(1-methylindazol-5-yl)pyrazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]prop-2-en-1-one; 1-{6-[(4M)-4-(5-chloro-6-methyl-1H-indazol-4-yl)-5- methyl-3-(1-methyl-1H-indazol-5-yl)-1H-pyrazol-1-yl]-2- azaspiro[3.3]heptan-2-yl}prop-2-en-1-one; 1-{6-[(4M)-4-(5-Chloro-6-methyl-1H-indazol-4-yl)-5-methyl-3-(1-methyl-1H-indazol-5-yl)-1H-pyrazol-1-yl]-2-azaspiro[3.3]heptan-2-yl}prop-2-en-1-one; 2653994-08-0; 2653994-10-4; 2-Propen-1-one, 1-[6-[(4R)-4-(5-chloro-6-methyl-1H-indazol-4-yl)-5-methyl-3-(1-methyl-1H-indazol-5-yl)-1H-pyrazol-1-yl]-2-azaspiro[3.3]hept-2-yl]-; AKOS040757949; AT36708; BDBM50579985; CHEMBL5077861; compound 5 [PMID: 35404998]; CS-0226220; CS-0311034; EX-A5693; example 1a [WO2021120890A1]; GLXC-25533; GTPL11715; HY-139612A; JDQ 443; JDQ 443 [WHO-DD]; JDQ443; JDQ-443; MS-29737; NSC846146; NSC-846146; NVP-JDQ443; NVP-JDQ-443; Opnurasib; opnurasib [INN]; -PROPEN-1-ONE, 1-(6-((4R)-4-(5-CHLORO-6-METHYL-1H-INDAZOL-4-YL)-5-METHYL-3-(1-METHYL-1H-INDAZOL-5-YL)-1H-PYRAZOL-1-YL)-2-AZASPIRO(3.3)HEPT-2-YL)-; Q3W0H3V1LQ; SCHEMBL23533580
    Click to Show/Hide
External Link
CID: 156501355
TTD: D37IQM
 Compound Name TRS003 Phase 3 [42]
External Link
TTD: D2KVG4
 Compound Name Tusamitamab ravtansine Phase 3 [43]
Synonyms
SAR408701
    Click to Show/Hide
External Link
TTD: D2D6NJ
 Compound Name RG6058 Phase 3 [44]
Synonyms
Tiragolumab
    Click to Show/Hide
External Link
TTD: D0L4VD
 Compound Name GSK4069889 Phase 2 [45]
Synonyms
TSR-022
    Click to Show/Hide
External Link
TTD: DZW53X
 Compound Name APL-101 Phase 2 [46]
Synonyms
Bozitinib; PLB-1001; 1440964-89-5; Vebreltinib; Vebreltinib [USAN]; UNII-2WZP8A9VFN; 2WZP8A9VFN; Bozitinib (PLB-1001); SCHEMBL15594471; BDBM107096; CBI-3103; s6762; WHO 11677; HY-125017; CS-0088607; US9695175, 44; 1,2,4-Triazolo(4,3-b)pyridazine, 6-(1-cyclopropyl-1H-pyrazol-4-yl)-3-(difluoro(6- fluoro-2-methyl-2H-indazol-5-yl)methyl)-; 6-(1-Cyclopropyl-1H-pyrazol-4-yl)-3-(difluoro(6-fluoro-2-methyl-2H-indazol-5- yl)methyl)-1,2,4-triazolo(4,3-b)pyridazine
    Click to Show/Hide
External Link
CID: 72202701
TTD: DV3Y7F
 Compound Name SGN-LIV1A Phase 2 [47]
Synonyms
Ladiratuzumab Vedotin
    Click to Show/Hide
External Link
TTD: DS6B1L
 Compound Name BNT116 Phase 2 [48]
External Link
TTD: DR39GZ
 Compound Name AZD7789 Phase 2 [49]
External Link
TTD: DNI7E3
 Compound Name L-DOS47 Phase 1/2 [50]
External Link
TTD: DN3Z5D
 Compound Name NC318 Phase 2 [51]
External Link
TTD: D9UZ5Q
 Compound Name Vorolanib Phase 2 [52]
Synonyms
UNII-YP8G3I74EL; YP8G3I74EL; 1013920-15-4; (S,Z)-N-(1-(Dimethylcarbamoyl)pyrrolidin-3-yl)-5-((5-fluoro-2-oxoindolin-3-ylidene)methyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide; Vorolanib [INN]; SCHEMBL2439528; CHEMBL4297587; N-((3S)-1-(dimethylcarbamoyl)pyrrolidin-3-yl)-5-((Z)-(5-fluoro-2-oxo-1H-indol-3-ylidene)methyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide; s6843; DB15247; HY-109019; CS-0030517; Q27294638; 1H-Pyrrole-3-carboxamide, N-((3S)-1-((dimethylamino)carbonyl)-3-pyrrolidinyl)-5-((Z)-(5-fluoro-1,2-dihydro-2-oxo-3H-indol-3-ylidene)methyl)-2,4-dimethyl-
    Click to Show/Hide
External Link
CID: 59215954
TTD: D8AG3S
DrugBank: DB15247
 Compound Name Xofigo Phase 2 [53]
External Link
TTD: D6B7FP
 Compound Name Bintrafusp alfa Phase 2 [54]
External Link
TTD: D5J3BL
 Compound Name Voyager-V1 Phase 2 [55]
Synonyms
VSV-IFNBeta-NIS
    Click to Show/Hide
External Link
TTD: D4AGB6
 Compound Name AB-106 Phase 2 [56]
Synonyms
DS6051b; GTPL11198; AB106
    Click to Show/Hide
External Link
CID: 154699459
TTD: D2KV8B
 Compound Name RO-5126766 Phase 2 [57]
Synonyms
VS-6766; CH-5126766; Dual Raf/MEK protein kinase inhibitor (cancer), Roche
    Click to Show/Hide
External Link
CID: 16719221
TTD: D0M6BD
DrugBank: DB15254
 Compound Name TC-210 Phase 1/2 [58]
External Link
TTD: DX6O9V
 Compound Name EMB-01 Phase 1/2 [59]
External Link
TTD: DWQ6J1
 Compound Name NM21-1480 Phase 1/2 [60]
External Link
TTD: DUVH60
 Compound Name MRx0518 Phase 1/2 [61]
External Link
TTD: DP4J2K
 Compound Name DZD9008 Phase 1/2 [62]
External Link
TTD: DM8Y2N
 Compound Name BGB-A425 Phase 1/2 [63]
External Link
TTD: D7UIZ1
 Compound Name Rilvegostomig Phase 1/2 [64]
Synonyms
AZD2936
    Click to Show/Hide
External Link
TTD: D4RMC9
 Compound Name IK-007 Phase 1/2 [65]
Synonyms
grapiprant
    Click to Show/Hide
External Link
TTD: D1KES8
 Compound Name IBI318 Phase 1 [66]
External Link
TTD: DX30BA
 Compound Name GEN-011 Phase 1 [67]
External Link
TTD: DR1YQ7
 Compound Name ENV-105 Phase 1 [68]
Synonyms
Carotuximab
    Click to Show/Hide
External Link
TTD: DQ8K3R
 Compound Name AMG 160 Phase 1 [69]
External Link
TTD: DOY4E6
 Compound Name ADP-A2M10 Phase 1 [70]
External Link
TTD: DM38KC
 Compound Name MEDI5752 Phase 1 [71]
External Link
TTD: D7L1MP
 Compound Name PF-07104091 Phase 1 [72]
External Link
TTD: D5TH2B
 Compound Name PF-06936308 Phase 1 [73]
External Link
TTD: D2LUK7
 Compound Name GEM3PSCA Phase 1 [74]
External Link
TTD: D1L7DE
 Compound Name PF-07257876 Phase 1 [75]
External Link
TTD: D1A7OP
 Compound Name Cosibelimab Phase 1 [76]
Synonyms
CK-301/TG-1501
    Click to Show/Hide
External Link
TTD: D17URP
 Compound Name Gemcitabine Approved [77]
External Link
CID: 60750
TTD: D0AJ3K
DrugBank: DB00441
 Compound Name SMI-4a Investigative [78]
Synonyms
438190-29-5; SMI 4a; TCS PIM-1 4a; (Z)-SMI-4a; (Z)-5-(3-(trifluoromethyl)benzylidene)thiazolidine-2,4-dione; (5Z)-5-[3-(trifluoromethyl)benzylidene]-1,3-thiazolidine-2,4-dione; CHEMBL183906; (5Z)-5-[[3-(TRIFLUOROMETHYL)PHENYL]METHYLENE]-2,4-THIAZOLIDINEDIONE; (5Z)-5-[[3-(trifluoromethyl)phenyl]methylidene]-1,3-thiazolidine-2,4-dione; 327033-36-3; C11H6F3NO2S; (Z)-5-(3-(Trifluoromethyl)benzylidene)-thiazolidine-2,4-dione; (5Z)-5-{[3-(trifluoromethyl)phenyl]methylidene}-1,3-thiazolidine-2,4-dione; Pim inhibitor 4a; 3vc4; SMI-4q; TCS PIM-1-4a; 5-(3-(Trifluoromethyl)benzylidene)thiazolidine-2,4-dione; 5-[3-(Trifluoromethyl)benzylidene]thiazolidine-2,4-dione; cc-717; thiazolidine-2,4-dione, 4a; SCHEMBL2541382; SCHEMBL2541388; BDBM26626; AOB6260; EX-A111; SYN1113; BDBM138364; HMS3229J21; 2720AH; HY-16576A; MFCD01152003; s8005; ZINC12576047; AKOS001314163; SMI-4a, >=98% (HPLC); CCG-265027; NCGC00345836-02; NCGC00345836-14; AC-32861; HY-15474; AB0165836; EC-000.2291; J3.561.866J; A11945; W-5256; US8877795, 12; Q27451064; 5-[[3-(trifluoromethyl)phenyl]methylene]-2,4-thiazolidinedione
    Click to Show/Hide
External Link
CID: 1361334
TTD: DAJ3D2
References
Ref 1 Stimulation of Let-7 Maturation by Metformin Improved the Response to Tyrosine Kinase Inhibitor Therapy in an m6A Dependent Manner. Front Oncol. 2022 Jan 6;11:731561. doi: 10.3389/fonc.2021.731561. eCollection 2021.
Ref 2 Methyltransferase-like 3 promotes the progression of lung cancer via activating PI3K/AKT/mTOR pathway. Clin Exp Pharmacol Physiol. 2022 Jul;49(7):748-758. doi: 10.1111/1440-1681.13647. Epub 2022 May 23.
Ref 3 DNA methyltransferase inhibitors: an updated patent review (2012-2015). Expert Opin Ther Pat. 2016 Sep;26(9):1017-30. doi: 10.1080/13543776.2016.1209488. Epub 2016 Jul 18.
Ref 4 FDA Approved Drug Products from FDA Official Website. 2023. Application Number: 218197
Ref 5 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
Ref 6 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 1479).
Ref 7 CenterWatch. Drugs in Clinical Trials Database. CenterWatch. 2008.
Ref 8 Pre-clinical and Clinical Safety Studies of CMX-2043: a cytoprotective lipoic acid analogue for ischaemia-reperfusion injury. Basic Clin Pharmacol Toxicol. 2014 Nov;115(5):456-64. doi: 10.1111/bcpt.12254. Epub 2014 May 16.
Ref 9 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
Ref 10 A comparison of physicochemical property profiles of marketed oral drugs and orally bioavailable anti-cancer protein kinase inhibitors in clinical development. Curr Top Med Chem. 2007;7(14):1408-22.
Ref 11 Discovery of a 2,4-disubstituted pyrrolo[1,2-f][1,2,4]triazine inhibitor (BMS-754807) of insulin-like growth factor receptor (IGF-1R) kinase in clinical development. J Med Chem. 2009 Dec 10;52(23):7360-3. doi: 10.1021/jm900786r.
Ref 12 Cancer stem cell (CSC) inhibitors: a review of recent patents (2012-2015). Expert Opin Ther Pat. 2017 Jul;27(7):753-761. doi: 10.1080/13543776.2017.1325465. Epub 2017 May 5.
Ref 13 Raft nanodomains contribute to Akt/PKB plasma membrane recruitment and activation. Nat Chem Biol. 2008 Sep;4(9):538-47. doi: 10.1038/nchembio.103. Epub 2008 Jul 20.
Ref 14 Comprehensive analysis of kinase inhibitor selectivity. Nat Biotechnol. 2011 Oct 30;29(11):1046-51. doi: 10.1038/nbt.1990.
Ref 15 The PI3K/Akt pathway as a target in the treatment of hematologic malignancies. Anticancer Agents Med Chem. 2009 Jun;9(5):550-9. doi: 10.2174/187152009788451851.
Ref 16 Syntheses of potent, selective, and orally bioavailable indazole-pyridine series of protein kinase B/Akt inhibitors with reduced hypotension. J Med Chem. 2007 Jun 28;50(13):2990-3003.
Ref 17 A phthalide with in vitro growth inhibitory activity from an oidiodendron strain. J Nat Prod. 2004 Dec;67(12):2086-9. doi: 10.1021/np040123n.
Ref 18 Indolinone based phosphoinositide-dependent kinase-1 (PDK1) inhibitors. Part 1: design, synthesis and biological activity. Bioorg Med Chem Lett. 2007 Jul 15;17(14):3814-8. doi: 10.1016/j.bmcl.2007.04.071. Epub 2007 Apr 27.
Ref 19 How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
Ref 20 Allosteric Akt (PKB) inhibitors: discovery and SAR of isozyme selective inhibitors. Bioorg Med Chem Lett. 2005 Feb 1;15(3):761-4.
Ref 21 Identification of 4-(2-(4-amino-1,2,5-oxadiazol-3-yl)-1-ethyl-7-{[(3S)-3-piperidinylmethyl]oxy}-1H-imidazo[4,5-c]pyridin-4-yl)-2-methyl-3-butyn-2-ol (GSK690693), a novel inhibitor of AKT kinase. J Med Chem. 2008 Sep 25;51(18):5663-79. doi: 10.1021/jm8004527.
Ref 22 2,3,5-Trisubstituted pyridines as selective AKT inhibitors. Part II: Improved drug-like properties and kinase selectivity from azaindazoles. Bioorg Med Chem Lett. 2010 Jan 15;20(2):679-83. doi: 10.1016/j.bmcl.2009.11.060. Epub 2009 Nov 20.
Ref 23 Specificity and mechanism of action of some commonly used protein kinase inhibitors. Biochem J. 2000 Oct 1;351(Pt 1):95-105. doi: 10.1042/0264-6021:3510095.
Ref 24 Discovery of a (1H-benzoimidazol-2-yl)-1H-pyridin-2-one (BMS-536924) inhibitor of insulin-like growth factor I receptor kinase with in vivo antitumor activity. J Med Chem. 2005 Sep 8;48(18):5639-43. doi: 10.1021/jm050392q.
Ref 25 Optimization of protein kinase CK2 inhibitors derived from 4,5,6,7-tetrabromobenzimidazole. J Med Chem. 2004 Dec 2;47(25):6239-47. doi: 10.1021/jm049854a.
Ref 26 4-arylazo-3,5-diamino-1H-pyrazole CDK inhibitors: SAR study, crystal structure in complex with CDK2, selectivity, and cellular effects. J Med Chem. 2006 Nov 2;49(22):6500-9. doi: 10.1021/jm0605740.
Ref 27 FDA Approved Drug Products from FDA Official Website. 2022. Application Number: 216340.
Ref 28 FDA Approved Drug Products from FDA Official Website. 2022. Application Number: 761210.
Ref 29 ClinicalTrials.gov (NCT04129502) TAK-788 as First-line Treatment Versus Platinum-Based Chemotherapy for Non-Small Cell Lung Cancer (NSCLC) With EGFR Exon 20 Insertion Mutations. U.S. National Institutes of Health.
Ref 30 Sugemalimab: First Approval. Drugs. 2022 Apr;82(5):593-599.
Ref 31 ClinicalTrials.gov (NCT05089734) Open-Label, Global, Multicenter, Randomized, Phase 3 Study of Sacituzumab Govitecan Versus Docetaxel in Patients With Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) With Progression on or After Platinum-Based Chemotherapy and Anti-PD-1/PD-L1 Immunotherapy. U.S.National Institutes of Health.
Ref 32 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
Ref 33 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2021
Ref 34 FDA Approved Drug Products from FDA Official Website. 2023. Application Number: 214665.
Ref 35 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
Ref 36 FDA Approved Drug Products from FDA Official Website. 2023. Application Number: 218213
Ref 37 ClinicalTrials.gov (NCT04633564) Multicenter, Double-Blind, Randomized, Parallel-Group Study to Assess the Efficacy and Safety of MYL-1402O Compared With Avastin?, in the First-line Treatment of Patients With Stage IV Non-Squamous Non-Small Cell Lung Cancer. U.S.National Institutes of Health.
Ref 38 ClinicalTrials.gov (NCT04736173) Study to Evaluate Monotherapy Compared to Combination Immunotherapies in Participants With PD-L1 Positive Non-small Cell Lung Cancer. U.S. National Institutes of Health.
Ref 39 ClinicalTrials.gov (NCT05555732) A Randomized Phase 3 Study of Datopotamab Deruxtecan (Dato-DXd) and Pembrolizumab With or Without Platinum Chemotherapy in Subjects With No Prior Therapy for Advanced or Metastatic PD-L1 TPS <50% Non-squamous Non-small Cell Lung Cancer Without Actionable Genomic Alterations (TROPION-Lung07). U.S.National Institutes of Health.
Ref 40 ClinicalTrials.gov (NCT03728556) A Study of CS1001 in Subjects With Stage III Non-Small Cell Lung Cancer. U.S. National Institutes of Health.
Ref 41 ClinicalTrials.gov (NCT05132075) A Randomized, Controlled, Open Label, Phase III Study Evaluating the Efficacy and Safety of JDQ443 Versus Docetaxel in Previously Treated Subjects With Locally Advanced or Metastatic KRAS G12C Mutant Non-small Cell Lung Cancer. U.S.National Institutes of Health.
Ref 42 ClinicalTrials.gov (NCT04416035) A Phase 3, Multicenter, Randomized and Double-Blind Study to Assess the Similarity in Efficacy and Safety Between TRS003 and China-approved Bevacizumab in Subjects With Advanced Nonsquamous NSCLC. U.S.National Institutes of Health.
Ref 43 ClinicalTrials.gov (NCT05245071) Open-label, Phase 2 Study, Evaluating the Efficacy and Safety of Tusamitamab Ravtansine in Non-squamous Non-small-cell Lung Cancer (NSQ NSCLC) Participants With Negative or Moderate CEACAM5 Expression Tumors and High Circulating CEA. U.S.National Institutes of Health.
Ref 44 ClinicalTrials.gov (NCT04294810) A Study of Tiragolumab in Combination With Atezolizumab Compared With Placebo in Combination With Atezolizumab in Patients With Previously Untreated Locally Advanced Unresectable or Metastatic PD-L1-Selected Non-Small Cell Lung Cancer (SKYSCRAPER-01). U.S. National Institutes of Health.
Ref 45 ClinicalTrials.gov (NCT04655976) Study of Cobolimab in Combination With Dostarlimab and Docetaxel in Advanced NSCLC Participants (COSTAR Lung). U.S. National Institutes of Health.
Ref 46 ClinicalTrials.gov (NCT04258033) A Study of PLB1001 in Non-small Cell Lung Cancer With c-Met Dysregulation. U.S. National Institutes of Health.
Ref 47 ClinicalTrials.gov (NCT04032704) A Study of Ladiratuzumab Vedotin in Advanced Solid Tumors. U.S. National Institutes of Health.
Ref 48 ClinicalTrials.gov (NCT05557591) A Phase 2 Study of Cemiplimab (Anti-PD-1 Antibody) in Combination With BNT116 (FixVac Lung) Versus Cemiplimab Monotherapy in First-Line Treatment of Patients With Advanced Non-Small Cell Lung Cancer (NSCLC) With Tumors Expressing PD-L1 >=50%. U.S.National Institutes of Health.
Ref 49 ClinicalTrials.gov (NCT04931654) A Phase I/IIa Open-label Dose Escalation and Expansion Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of AZD7789, an Anti-PD-1 and Anti-TIM-3 Bispecific Antibody, in Participants With Advanced or Metastatic Solid Tumors. U.S.National Institutes of Health.
Ref 50 ClinicalTrials.gov (NCT02340208) A Phase I/II Open-Label, Non-Randomized Dose Escalation Study of Immunoconjugate L-DOS47. U.S. National Institutes of Health.
Ref 51 ClinicalTrials.gov (NCT04699123) The Study of NC318 Alone or in Combination With Pembrolizumab in Patients With Advanced Non-small Cell Lung Cancer. U.S. National Institutes of Health.
Ref 52 ClinicalTrials.gov (NCT03848611) CM082 and JS001 in Patients With Advanced Non-Small Cell Lung Cancer (NSCLC).. U.S. National Institutes of Health.
Ref 53 ClinicalTrials.gov (NCT02283749) BrUOG L301: Xofigo Following Frontline-Line Chemotherapy For Patients With Non-Small Cell Lung Cancer and Bone Metastases. U.S.National Institutes of Health.
Ref 54 ClinicalTrials.gov (NCT04560686) Bintrafusp Alfa Before Surgery for the Treatment of Untreated Resectable Non-small Cell Lung Cancer. U.S. National Institutes of Health.
Ref 55 ClinicalTrials.gov (NCT04291105) Phase 2 Trial of Voyager V1 in Combination With Cemiplimab in Cancer Patients. U.S. National Institutes of Health.
Ref 56 ClinicalTrials.gov (NCT04395677) A Study of AB-106 in Subjects With Advanced NSCLC Harboring ROS1 Fusion Gene. U.S. National Institutes of Health.
Ref 57 ClinicalTrials.gov (NCT04625270) A Study of VS-6766 v. VS-6766 + Defactinib in Recurrent Low-Grade Serous Ovarian Cancer With and Without a KRAS Mutation. U.S. National Institutes of Health.
Ref 58 ClinicalTrials.gov (NCT03907852) Phase 1/2 Trial of Gavo-cel (TC-210) in Patients With Advanced Mesothelin-Expressing Cancer. U.S. National Institutes of Health.
Ref 59 ClinicalTrials.gov (NCT03797391) A Dose Escalation Study of EMB-01 in Participants With Advanced/Metastatic Solid Tumors. U.S. National Institutes of Health.
Ref 60 ClinicalTrials.gov (NCT04442126) A Study of NM21-1480 in Adult Patients With Advanced Solid Tumors. U.S. National Institutes of Health.
Ref 61 ClinicalTrials.gov (NCT03637803) Live Biotherapeutic Product MRx0518 and Pembrolizumab Combination Study in Solid Tumors. U.S. National Institutes of Health.
Ref 62 ClinicalTrials.gov (NCT03974022) Assessing an Oral EGFR Inhibitor, DZD9008 in Patients Who Have Advanced Non-small Cell Lung Cancer With EGFR or HER2 Mutation (WU-KONG1). U.S. National Institutes of Health.
Ref 63 ClinicalTrials.gov (NCT03744468) Study of BGB-A425 in Combination With Tislelizumab in Advanced Solid Tumors. U.S. National Institutes of Health.
Ref 64 ClinicalTrials.gov (NCT04995523) Phase I/II, Open-label, Dose Escalation and Dose Expansion Study to Evaluate Safety, Pharmacokinetics, Pharmacodynamics and Efficacy of AZD2936 Anti-TIGIT/Anti-PD-1 Bispecific Antibody in Participants With Advanced or Metastatic NSCLC. U.S.National Institutes of Health.
Ref 65 ClinicalTrials.gov (NCT03696212) Open Label, Single Arm, Phase 1b/2 Study to Evaluate the Safety and Efficacy of Grapiprant (ARY-007) in Combination With Pembrolizumab in Patients With Advanced or Metastatic Post-PD-1/L1 Non-Small Cell Lung Cancer (NSCLC) Adenocarcinoma. U.S.National Institutes of Health.
Ref 66 ClinicalTrials.gov (NCT04777084) The Efficacy and Safety of the Bispecific Anti-PD-1/PD-L1 Antibody IBI318 Combined With Lenvatinib in NSCLC.. U.S. National Institutes of Health.
Ref 67 ClinicalTrials.gov (NCT04596033) TiTAN-1: Safety, Proliferation and Persistence of GEN-011 Autologous Cell Therapy. U.S. National Institutes of Health.
Ref 68 ClinicalTrials.gov (NCT05401110) IIT2021-12-Reckamp-Osi105: Phase I Study of Osimertinib With Carotuximab in Advanced, EGFR-mutated Non-Small Cell Lung Cancer. U.S.National Institutes of Health.
Ref 69 ClinicalTrials.gov (NCT04822298) Study of AMG 160 in Subjects With Non-Small Cell Lung Cancer. U.S. National Institutes of Health.
Ref 70 Phase I clinical trial evaluating the safety and efficacy of ADP-A2M10 SPEAR T cells in patients with MAGE-A10(+) advanced non-small cell lung cancer. J Immunother Cancer. 2022 Jan;10(1):e003581.
Ref 71 ClinicalTrials.gov (NCT03819465) A Study of Novel Anti-cancer Agents in Patients With Previously Untreated NSCLC (MAGELLAN). U.S. National Institutes of Health.
Ref 72 ClinicalTrials.gov (NCT04553133) PF-07104091 as a Single Agent and in Combination Therapy. U.S. National Institutes of Health.
Ref 73 ClinicalTrials.gov (NCT03674827) Vaccine-Based Immunotherapy Regimen For NSCLC and TNBC. U.S. National Institutes of Health.
Ref 74 ClinicalTrials.gov (NCT03927573) Study With Bispecific Antibody Engaging T-cells, in Patients With Progressive Cancer Diseases With Positive PSCA Marker. U.S. National Institutes of Health.
Ref 75 ClinicalTrials.gov (NCT04881045) A PHASE 1 DOSE ESCALATION AND EXPANSION STUDY EVALUATING THE SAFETY, TOLERABILITY, PHARMACOKINETICS, PHARMACODYNAMICS, AND ANTITUMOR ACTIVITY OF PF-07257876 IN PATIENTS WITH ADVANCED OR METASTATIC TUMORS. U.S.National Institutes of Health.
Ref 76 ClinicalTrials.gov (NCT04786964) Study of Pemetrexed+Platinum Chemotherapy With or Without Cosibelimab (CK-301) in First Line Metastatic Non-squamous Non-Small Cell Lung Cancer (CONTERNO). U.S. National Institutes of Health.
Ref 77 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
Ref 78 Pim-1 inhibitor SMI-4a suppresses tumor growth in non-small cell lung cancer via PI3K/AKT/mTOR pathway. Onco Targets Ther. 2019 Apr 23;12:3043-3050.