Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT02175
[1], [2]
DNA methylation DNMT3A METTL3 Direct Inhibition m6A modification PIK3CA PIK3CA METTL3 Methylation : m6A sites
m6A Modification:
m6A Regulator Methyltransferase-like 3 (METTL3) WRITER
m6A Target PI3-kinase subunit alpha (PI3k/PIK3CA)
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 PI3-kinase subunit alpha (PI3k/PIK3CA)/AKT/mTOR pathway.
Responsed Disease Lung cancer ICD-11: 2C25
Responsed Drug Osimertinib
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
 Compound Name PMID27376512-Compound-Figure3CG Patented [3]
MOA Inhibitor
Activity EC50 = 2400 nM
External Link
 Compound Name PMID27376512-Compound-Figure3CM Patented [3]
MOA Inhibitor
Activity EC50 = 1100 nM
External Link
 Compound Name PMID27376512-Compound-Figure2aExample1 Patented [3]
MOA Inhibitor
Activity IC50 = 3000 nM
External Link
 Compound Name PMID27376512-Compound-MTC-424 Patented [3]
MOA Inhibitor
Activity IC50 = 1940 nM
External Link
 Compound Name PMID27376512-Compound-MTC-427 Patented [3]
MOA Inhibitor
Activity IC50 = 295 nM
External Link
 Compound Name PMID27376512-Compound-MTC-422 Patented [3]
MOA Inhibitor
Activity IC50 = 1430 nM
External Link
 Compound Name PMID27376512-Compound-MTC-423 Patented [3]
MOA Inhibitor
Activity IC50 = 363 nM
External Link
PI3-kinase subunit alpha (PI3k/PIK3CA) 12 Compound(s) Regulating the Target Click to Show/Hide the Full List
 Compound Name Alpelisib Approved [4]
Synonyms
1217486-61-7; BYL-719; BYL719; UNII-08W5N2C97Q; BYL 719; Alpelisib (BYL719); (S)-N1-(4-Methyl-5-(2-(1,1,1-trifluoro-2-methylpropan-2-yl)pyridin-4-yl)thiazol-2-yl)pyrrolidine-1,2-dicarboxamide; NVP-BYL719; (2S)-N1-[4-Methyl-5-[2-(2,2,2-trifluoro-1,1-dimethylethyl)-4-pyridinyl]-2-thiazolyl]-1,2-pyrrolidinedicarboxamide; CHEMBL2396661; 08W5N2C97Q; AK146107; C19H22F3N5O2S; (S)-N1-(4-Methyl-5-(2-(1,1,1-trifluoro-2-methylpropan-2-yl)-pyridin-4-yl)thiazol-2-yl)pyrrolidine-1,2-dicarboxamide
    Click to Show/Hide
MOA Inhibitor
Activity IC50 = 5 nM
External Link
 Compound Name BAY 80-6946 Approved [5]
Synonyms
Copanlisib; BAY-80-6946; Aliqopa; UNII-WI6V529FZ9; BAY80-6946; WI6V529FZ9; AK172384; BAY 80-6946 (Copanlisib); Copanlisib [USAN:INN]; Copanlisib (USAN/INN); GTPL7875; SCHEMBL1655478; SCHEMBL13084037; Copanlisib (BAY 80-6946); DTXS
    Click to Show/Hide
MOA Inhibitor
Activity IC50 = 0.5 nM
External Link
 Compound Name GDC-0032 Phase 2/3 [6]
Synonyms
Taselisib; 1282512-48-4; GDC 0032; UNII-L08J2O299M; 2-(4-(2-(1-isopropyl-3-methyl-1H-1,2,4-triazol-5-yl)-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepin-9-yl)-1H-pyrazol-1-yl)-2-methylpropanamide; CHEMBL2387080; GDC0032; L08J2O299M; Taselisib [INN]; 2-Methyl-2-(4-{2-[3-Methyl-1-(Propan-2-Yl)-1h-1,2,4-Triazol-5-Yl]-5,6-Dihydroimidazo[1,2-D][1,4]benzoxazepin-9-Yl}-1h-Pyrazol-1-Yl)propanamide; Taselisib [USAN:INN]; GTPL7794; SCHEMBL1485247; SYN1202; DTXSID00155842; BEUQXVWXFDOSAQ-UHFFFAOYSA-N
    Click to Show/Hide
MOA Modulator
Activity Ki = 0.29 nM
External Link
 Compound Name Buparlisib Phase 3 [7]
Synonyms
BKM120
    Click to Show/Hide
MOA Inhibitor
Activity Ki = 20 nM
External Link
 Compound Name LY3023414 Phase 2 [8]
MOA Modulator
External Link
 Compound Name MLN1117 Phase 1/2 [9]
MOA Inhibitor
Activity IC50 = 15 nM
External Link
 Compound Name PA-799 Phase 1/2 [10]
Synonyms
MEN1611; CH-5033855; CH-5061565; CH-5089788; CH-5108135; CH-5111436; CH-5138134
    Click to Show/Hide
MOA Inhibitor
External Link
 Compound Name BLY719 Phase 1 [11]
MOA Inhibitor
External Link
 Compound Name LY3849524 Phase 1 [12]
Synonyms
LOXO 783
    Click to Show/Hide
MOA Inhibitor
External Link
 Compound Name HHCYH33 Phase 1 [13]
Synonyms
CYH33; UNII-RCA38L4HB5; RCA38L4HB5; 1494684-28-4; Methyl (5-(6-((4-(methylsulfonyl)piperazin-1-yl)methyl)-4-morpholinopyrrolo[2,1-f][1,2,4]triazin-2-yl)-4-(trifluoromethyl)pyridin-2-yl)carbamate; CYH 33; CYH-33; SCHEMBL16622890; BDBM330295; HY-123938; CS-0087546; US9724352, I-33; Carbamic acid, N-(5-(6-((4-(methylsulfonyl)-1-piperazinyl)methyl)-4-(4-morpholinyl)pyrrolo(2,1-F)(1,2,4)triazin-2-yl)-4-(trifluoromethyl)-2-pyridinyl)-, methyl ester; Methyl N-(5-(6-((4-(methylsulfonyl)-1-piperazinyl)methyl)-4-(4-morpholinyl)pyrrolo(2,1-F)(1,2,4)triazin-2-yl)-4-(trifluoromethyl)-2-pyridinyl)carbamate; methyl N-[5-[6-[(4-methylsulfonylpiperazin-1-yl)methyl]-4-morpholin-4-ylpyrrolo[2,1-f][1,2,4]triazin-2-yl]-4-(trifluoromethyl)pyridin-2-yl]carbamate
    Click to Show/Hide
MOA Inhibitor
External Link
 Compound Name PWT-33597 Phase 1 [14]
Synonyms
PI3 kinase alpha/mTOR dual inhibitor (cancer), Pathway Therapeutics
    Click to Show/Hide
MOA Modulator
External Link
 Compound Name ETP-46321 Investigative [15]
Synonyms
1252594-99-2; CHEMBL2087474; 5-(2-((4-(methylsulfonyl)piperazin-1-yl)methyl)-8-morpholinoimidazo[1,2-a]pyrazin-6-yl)pyrimidin-2-amine; 5-[2-[(4-methylsulfonylpiperazin-1-yl)methyl]-8-morpholin-4-ylimidazo[1,2-a]pyrazin-6-yl]pyrimidin-2-amine; SCHEMBL10100315; BCP19935; ETP46321; EX-A1284; BDBM50420714; ZINC68247289; CS-3350; ETP 46321;ETP46321; HY-12340; 5-[2-[(4-methylsulfonylpiperazin-1-yl)methyl]-8-morpholin-4-yl-imidazo[1,2-a]pyrazin-6-yl]pyrimidin-2-amine
    Click to Show/Hide
MOA Inhibitor
External Link
2C25: Lung cancer 52 Compound(s) Regulating the Disease Click to Show/Hide the Full List
 Compound Name Adagrasib Approved [16]
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
 Compound Name Amivantamab Approved [17]
External Link
 Compound Name Mobocertinib Approved [18]
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
 Compound Name Sugemalimab Approved in China [19]
External Link
 Compound Name Sacituzumab govitecan Approved [20]
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
 Compound Name Atezolizumab Approved [21]
External Link
 Compound Name Tepotinib Approved [22]
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
 Compound Name Sotorasib Approved [23]
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
 Compound Name Entrectinib Approved [24]
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
 Compound Name Repotrectinib Approved [25]
Synonyms
FIKPXCOQUIZNHB-RRKGBCIJSA-N; SCHEMBL20438940; TPX 0005; BCP19778
    Click to Show/Hide
External Link
 Compound Name MYL-1402O Phase 3 [26]
Synonyms
bevacizumab biosimilar
    Click to Show/Hide
External Link
 Compound Name AB154 Phase 3 [27]
Synonyms
Domvanalimab
    Click to Show/Hide
External Link
 Compound Name Datopotamab deruxtecan Phase 3 [28]
External Link
 Compound Name CS1001 Phase 3 [29]
External Link
 Compound Name JDQ443 Phase 3 [30]
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
 Compound Name TRS003 Phase 3 [31]
External Link
 Compound Name Tusamitamab ravtansine Phase 3 [32]
Synonyms
SAR408701
    Click to Show/Hide
External Link
 Compound Name RG6058 Phase 3 [33]
Synonyms
Tiragolumab
    Click to Show/Hide
External Link
 Compound Name GSK4069889 Phase 2 [34]
Synonyms
TSR-022
    Click to Show/Hide
External Link
 Compound Name APL-101 Phase 2 [35]
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
 Compound Name SGN-LIV1A Phase 2 [36]
Synonyms
Ladiratuzumab Vedotin
    Click to Show/Hide
External Link
 Compound Name BNT116 Phase 2 [37]
External Link
 Compound Name AZD7789 Phase 2 [38]
External Link
 Compound Name L-DOS47 Phase 1/2 [39]
External Link
 Compound Name NC318 Phase 2 [40]
External Link
 Compound Name Vorolanib Phase 2 [41]
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
 Compound Name Xofigo Phase 2 [42]
External Link
 Compound Name Bintrafusp alfa Phase 2 [43]
External Link
 Compound Name Voyager-V1 Phase 2 [44]
Synonyms
VSV-IFNBeta-NIS
    Click to Show/Hide
External Link
 Compound Name AB-106 Phase 2 [45]
Synonyms
DS6051b; GTPL11198; AB106
    Click to Show/Hide
External Link
 Compound Name RO-5126766 Phase 2 [46]
Synonyms
VS-6766; CH-5126766; Dual Raf/MEK protein kinase inhibitor (cancer), Roche
    Click to Show/Hide
External Link
 Compound Name TC-210 Phase 1/2 [47]
External Link
 Compound Name EMB-01 Phase 1/2 [48]
External Link
 Compound Name NM21-1480 Phase 1/2 [49]
External Link
 Compound Name MRx0518 Phase 1/2 [50]
External Link
 Compound Name DZD9008 Phase 1/2 [51]
External Link
 Compound Name BGB-A425 Phase 1/2 [52]
External Link
 Compound Name Rilvegostomig Phase 1/2 [53]
Synonyms
AZD2936
    Click to Show/Hide
External Link
 Compound Name IK-007 Phase 1/2 [54]
Synonyms
grapiprant
    Click to Show/Hide
External Link
 Compound Name IBI318 Phase 1 [55]
External Link
 Compound Name GEN-011 Phase 1 [56]
External Link
 Compound Name ENV-105 Phase 1 [57]
Synonyms
Carotuximab
    Click to Show/Hide
External Link
 Compound Name AMG 160 Phase 1 [58]
External Link
 Compound Name ADP-A2M10 Phase 1 [59]
External Link
 Compound Name MEDI5752 Phase 1 [60]
External Link
 Compound Name PF-07104091 Phase 1 [61]
External Link
 Compound Name PF-06936308 Phase 1 [62]
External Link
 Compound Name GEM3PSCA Phase 1 [63]
External Link
 Compound Name PF-07257876 Phase 1 [64]
External Link
 Compound Name Cosibelimab Phase 1 [65]
Synonyms
CK-301/TG-1501
    Click to Show/Hide
External Link
 Compound Name Gemcitabine Approved [66]
External Link
 Compound Name SMI-4a Investigative [67]
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
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 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
Ref 5 2017 FDA drug approvals. Nat Rev Drug Discov. 2018 Feb;17(2):81-85. doi: 10.1038/nrd.2018.4. Epub 2018 Jan 19.
Ref 6 Company report (BioOncology)
Ref 7 Targeting the phosphoinositide 3-kinase pathway in cancer. Nat Rev Drug Discov. 2009 Aug;8(8):627-44. doi: 10.1038/nrd2926.
Ref 8 Company report (Lilly)
Ref 9 National Cancer Institute Drug Dictionary (drug id 714372).
Ref 10 The selective class I PI3K inhibitor CH5132799 targets human cancers harboring oncogenic PIK3CA mutations. Clin Cancer Res. 2011 May 15;17(10):3272-81. doi: 10.1158/1078-0432.CCR-10-2882. Epub 2011 May 10.
Ref 11 In vitro anticancer activity of PI3K alpha selective inhibitor BYL719 in head and neck cancer. Anticancer Res. 2015 Jan;35(1):175-82.
Ref 12 ClinicalTrials.gov (NCT05307705) A Study of LOXO-783 Administered as Monotherapy and in Combination With Anticancer Therapies for Patients With Advanced Breast Cancer and Other Solid Tumors With a PIK3CA H1047R Mutation. U.S.National Institutes of Health.
Ref 13 Adaptive resistance to PI3KAlpha-selective inhibitor CYH33 is mediated by genomic and transcriptomic alterations in ESCC cells. Cell Death Dis. 2021 Jan 14;12(1):85. doi: 10.1038/s41419-020-03370-4.
Ref 14 Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics. 2005 Aug;86(2):127-41. doi: 10.1016/j.ygeno.2005.04.008.
Ref 15 ETP-46321, a dual p110Alpha/Delta class IA phosphoinositide 3-kinase inhibitor modulates T lymphocyte activation and collagen-induced arthritis. Biochem Pharmacol. 2016 Apr 15;106:56-69. doi: 10.1016/j.bcp.2016.02.005. Epub 2016 Feb 13.
Ref 16 FDA Approved Drug Products from FDA Official Website. 2022. Application Number: 216340.
Ref 17 FDA Approved Drug Products from FDA Official Website. 2022. Application Number: 761210.
Ref 18 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 19 Sugemalimab: First Approval. Drugs. 2022 Apr;82(5):593-599.
Ref 20 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 21 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
Ref 22 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2021
Ref 23 FDA Approved Drug Products from FDA Official Website. 2023. Application Number: 214665.
Ref 24 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
Ref 25 FDA Approved Drug Products from FDA Official Website. 2023. Application Number: 218213
Ref 26 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 27 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 28 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 29 ClinicalTrials.gov (NCT03728556) A Study of CS1001 in Subjects With Stage III Non-Small Cell Lung Cancer. U.S. National Institutes of Health.
Ref 30 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 31 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 32 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 33 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 34 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 35 ClinicalTrials.gov (NCT04258033) A Study of PLB1001 in Non-small Cell Lung Cancer With c-Met Dysregulation. U.S. National Institutes of Health.
Ref 36 ClinicalTrials.gov (NCT04032704) A Study of Ladiratuzumab Vedotin in Advanced Solid Tumors. U.S. National Institutes of Health.
Ref 37 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 38 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 39 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 40 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 41 ClinicalTrials.gov (NCT03848611) CM082 and JS001 in Patients With Advanced Non-Small Cell Lung Cancer (NSCLC).. U.S. National Institutes of Health.
Ref 42 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 43 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 44 ClinicalTrials.gov (NCT04291105) Phase 2 Trial of Voyager V1 in Combination With Cemiplimab in Cancer Patients. U.S. National Institutes of Health.
Ref 45 ClinicalTrials.gov (NCT04395677) A Study of AB-106 in Subjects With Advanced NSCLC Harboring ROS1 Fusion Gene. U.S. National Institutes of Health.
Ref 46 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 47 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 48 ClinicalTrials.gov (NCT03797391) A Dose Escalation Study of EMB-01 in Participants With Advanced/Metastatic Solid Tumors. U.S. National Institutes of Health.
Ref 49 ClinicalTrials.gov (NCT04442126) A Study of NM21-1480 in Adult Patients With Advanced Solid Tumors. U.S. National Institutes of Health.
Ref 50 ClinicalTrials.gov (NCT03637803) Live Biotherapeutic Product MRx0518 and Pembrolizumab Combination Study in Solid Tumors. U.S. National Institutes of Health.
Ref 51 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 52 ClinicalTrials.gov (NCT03744468) Study of BGB-A425 in Combination With Tislelizumab in Advanced Solid Tumors. U.S. National Institutes of Health.
Ref 53 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 54 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 55 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 56 ClinicalTrials.gov (NCT04596033) TiTAN-1: Safety, Proliferation and Persistence of GEN-011 Autologous Cell Therapy. U.S. National Institutes of Health.
Ref 57 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 58 ClinicalTrials.gov (NCT04822298) Study of AMG 160 in Subjects With Non-Small Cell Lung Cancer. U.S. National Institutes of Health.
Ref 59 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 60 ClinicalTrials.gov (NCT03819465) A Study of Novel Anti-cancer Agents in Patients With Previously Untreated NSCLC (MAGELLAN). U.S. National Institutes of Health.
Ref 61 ClinicalTrials.gov (NCT04553133) PF-07104091 as a Single Agent and in Combination Therapy. U.S. National Institutes of Health.
Ref 62 ClinicalTrials.gov (NCT03674827) Vaccine-Based Immunotherapy Regimen For NSCLC and TNBC. U.S. National Institutes of Health.
Ref 63 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 64 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 65 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 66 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
Ref 67 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.