m6A-centered Crosstalk Information

Mechanism of Crosstalk between m6A Modification and Epigenetic Regulation
Crosstalk ID
M6ACROT03384
 [1], [2]
Histone modification H3K27ac Epigenetic Regulator MIR570HG Indirect Inhibition m6A modification PTEN PTEN METTL3 Methylation : m6A sites
m6A Modification:
m6A Regulator Methyltransferase-like 3 (METTL3) WRITER
 Regulator Info 
m6A Target Mutated in multiple advanced cancers 1 (PTEN)
 Targert Gene 
Epigenetic Regulation that have Cross-talk with This m6A Modification:
Epigenetic Regulation Type Histone modification (HistMod)
Regulated Target Histone H3 lysine 27 acetylation (H3K27ac) View Details
Downstream Gene MIR570HG View Details
Crosstalk Relationship Histone modification  →  m6A Inhibition
Crosstalk Mechanism Histone modification indirectly regulates m6A modification through downstream signaling pathways
Crosstalk Summary Gain of H3K4me1 and Histone H3 lysine 27 acetylation (H3K27ac) led to the activation of MIR570HG expression. LINC00969 interacts with EZH2 and METTL3, transcriptionally regulates the level of H3K27me3 in the NLRP3 promoter region, and posttranscriptionally modifies the m6A level of NLRP3 in an m6A-YTHDF2-dependent manner Bete-elemene exerted the restrictive impacts on the cell growth of lung cancer in vivo and in vitro through targeting METTL3. Bete-elemene contributed to the augmented Mutated in multiple advanced cancers 1 (PTEN) expression via suppressing its m6A modification.
Responsed Disease Lung cancer ICD-11: 2C25
 Disease Info 
Responsed Drug Gefitinib
 Drug Info 
Cell Process Pyroptosis
In-vitro Model
 A-549 Lung adenocarcinoma Homo sapiens CVCL_0023
NCI-H1299 Lung large cell carcinoma Homo sapiens CVCL_0060
In-vivo Model Four-week-old BALB/c nude mice were randomly divided into three groups: (1) vector group, (2) vector + Bete-elemene group, and (3) Bete-elemene + METTL3 group. Nude mice were raised in an SPF level animal house and were free to eat and drink. Mice in the vector group were subcutaneously injected with lung cancer cells transfected with empty vector and did not receive Bete-elemene administration, and this group was implemented as the negative control. Following establishing orthotopic xenografts by using A549 or H1299 cells transfected with empty vector, mice in the vector + Bete-elemene group underwent intraperitoneal injection with Bete-elemene once a day. For the subcutaneous transplanted model, A549 or H1299 cells transfected with METTL3-overexpressing vector were inoculated into mice from the Bete-elemene + METTL3 group. Then, mice were intraperitoneally administrated with Bete-elemene once a day. Three weeks later, all the animals were euthanized with CO2. Xenografts were removed and weighted after mice were euthanatized.
Full List of Potential Compound(s) Related to This m6A-centered Crosstalk
2C25: Lung cancer 52 Compound(s) Regulating the Disease Click to Show/Hide the Full List
 Compound Name Adagrasib Approved [3]
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)-
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CID: 138611145
TTD: DUQV41
 Compound Name Amivantamab Approved [4]
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TTD: DQ5X1Z
 Compound Name Mobocertinib Approved [5]
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
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CID: 118607832
TTD: DI4HA7
 Compound Name Sugemalimab Approved in China [6]
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TTD: DDZ48Y
 Compound Name Sacituzumab govitecan Approved [7]
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
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CID: 91668186
TTD: D8LAE2
 Compound Name Atezolizumab Approved [8]
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TTD: D0YM2K
 Compound Name Tepotinib Approved [9]
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
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CID: 25171648
TTD: D0R8QG
DrugBank: DB15133
 Compound Name Sotorasib Approved [10]
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)-
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CID: 137278711
TTD: D0R7LD
DrugBank: DB15569
 Compound Name Entrectinib Approved [11]
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
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CID: 25141092
TTD: D0O0LS
DrugBank: DB11986
 Compound Name Repotrectinib Approved [12]
Synonyms
FIKPXCOQUIZNHB-RRKGBCIJSA-N; SCHEMBL20438940; TPX 0005; BCP19778
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CID: 135565923
TTD: D05NFR
 Compound Name MYL-1402O Phase 3 [13]
Synonyms
bevacizumab biosimilar
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TTD: DYH3Q6
 Compound Name AB154 Phase 3 [14]
Synonyms
Domvanalimab
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TTD: DT1FS0
 Compound Name Datopotamab deruxtecan Phase 3 [15]
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TTD: DP41HV
 Compound Name CS1001 Phase 3 [16]
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TTD: D3MP1S
 Compound Name JDQ443 Phase 3 [17]
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
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CID: 156501355
TTD: D37IQM
 Compound Name TRS003 Phase 3 [18]
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TTD: D2KVG4
 Compound Name Tusamitamab ravtansine Phase 3 [19]
Synonyms
SAR408701
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TTD: D2D6NJ
 Compound Name RG6058 Phase 3 [20]
Synonyms
Tiragolumab
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TTD: D0L4VD
 Compound Name GSK4069889 Phase 2 [21]
Synonyms
TSR-022
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TTD: DZW53X
 Compound Name APL-101 Phase 2 [22]
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
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CID: 72202701
TTD: DV3Y7F
 Compound Name SGN-LIV1A Phase 2 [23]
Synonyms
Ladiratuzumab Vedotin
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TTD: DS6B1L
 Compound Name BNT116 Phase 2 [24]
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TTD: DR39GZ
 Compound Name AZD7789 Phase 2 [25]
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TTD: DNI7E3
 Compound Name L-DOS47 Phase 1/2 [26]
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TTD: DN3Z5D
 Compound Name NC318 Phase 2 [27]
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TTD: D9UZ5Q
 Compound Name Vorolanib Phase 2 [28]
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-
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CID: 59215954
TTD: D8AG3S
DrugBank: DB15247
 Compound Name Xofigo Phase 2 [29]
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TTD: D6B7FP
 Compound Name Bintrafusp alfa Phase 2 [30]
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TTD: D5J3BL
 Compound Name Voyager-V1 Phase 2 [31]
Synonyms
VSV-IFNBeta-NIS
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TTD: D4AGB6
 Compound Name AB-106 Phase 2 [32]
Synonyms
DS6051b; GTPL11198; AB106
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CID: 154699459
TTD: D2KV8B
 Compound Name RO-5126766 Phase 2 [33]
Synonyms
VS-6766; CH-5126766; Dual Raf/MEK protein kinase inhibitor (cancer), Roche
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CID: 16719221
TTD: D0M6BD
DrugBank: DB15254
 Compound Name TC-210 Phase 1/2 [34]
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TTD: DX6O9V
 Compound Name EMB-01 Phase 1/2 [35]
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TTD: DWQ6J1
 Compound Name NM21-1480 Phase 1/2 [36]
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TTD: DUVH60
 Compound Name MRx0518 Phase 1/2 [37]
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TTD: DP4J2K
 Compound Name DZD9008 Phase 1/2 [38]
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TTD: DM8Y2N
 Compound Name BGB-A425 Phase 1/2 [39]
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TTD: D7UIZ1
 Compound Name Rilvegostomig Phase 1/2 [40]
Synonyms
AZD2936
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TTD: D4RMC9
 Compound Name IK-007 Phase 1/2 [41]
Synonyms
grapiprant
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TTD: D1KES8
 Compound Name IBI318 Phase 1 [42]
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TTD: DX30BA
 Compound Name GEN-011 Phase 1 [43]
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TTD: DR1YQ7
 Compound Name ENV-105 Phase 1 [44]
Synonyms
Carotuximab
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TTD: DQ8K3R
 Compound Name AMG 160 Phase 1 [45]
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TTD: DOY4E6
 Compound Name ADP-A2M10 Phase 1 [46]
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TTD: DM38KC
 Compound Name MEDI5752 Phase 1 [47]
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TTD: D7L1MP
 Compound Name PF-07104091 Phase 1 [48]
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TTD: D5TH2B
 Compound Name PF-06936308 Phase 1 [49]
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TTD: D2LUK7
 Compound Name GEM3PSCA Phase 1 [50]
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TTD: D1L7DE
 Compound Name PF-07257876 Phase 1 [51]
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TTD: D1A7OP
 Compound Name Cosibelimab Phase 1 [52]
Synonyms
CK-301/TG-1501
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TTD: D17URP
 Compound Name Gemcitabine Approved [53]
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CID: 60750
TTD: D0AJ3K
DrugBank: DB00441
 Compound Name SMI-4a Investigative [54]
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
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CID: 1361334
TTD: DAJ3D2
References
Ref 1 LncRNA LINC00969 promotes acquired gefitinib resistance by epigenetically suppressing of NLRP3 at transcriptional and posttranscriptional levels to inhibit pyroptosis in lung cancer. Cell Death Dis. 2023 May 8;14(5):312. doi: 10.1038/s41419-023-05840-x.
Ref 2 Beta-Elemene Restrains PTEN mRNA Degradation to Restrain the Growth of Lung Cancer Cells via METTL3-Mediated N(6) Methyladenosine Modification. J Oncol. 2022 Jan 12;2022:3472745. doi: 10.1155/2022/3472745. eCollection 2022.
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Ref 6 Sugemalimab: First Approval. Drugs. 2022 Apr;82(5):593-599.
Ref 7 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.
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Ref 12 FDA Approved Drug Products from FDA Official Website. 2023. Application Number: 218213
Ref 13 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 14 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.
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