m6A-centered Drug Response Information

General Information of the Drug (ID: M6ADRUG0073)
Name
CB-839
Synonyms
CB-839; 1439399-58-2; 2-(pyridin-2-yl)-N-(5-(4-(6-(2-(3-(trifluoromethoxy)phenyl)acetamido)pyridazin-3-yl)butyl)-1,3,4-thiadiazol-2-yl)acetamide; CB839; CB 839; UNII-U6CL98GLP4; U6CL98GLP4; N-[6-[4-[5-[(2-pyridin-2-ylacetyl)amino]-1,3,4-thiadiazol-2-yl]butyl]pyridazin-3-yl]-2-[3-(trifluoromethoxy)phenyl]acetamide; 2-(Pyridin-2-Yl)-N-(5-{4-[6-({[3-(Trifluoromethoxy)phenyl]acetyl}amino)pyridazin-3-Yl]butyl}-1,3,4-Thiadiazol-2-Yl)acetamide; 2-(PYRIDIN-2-YL)-N-{5-[4-(6-{2-[3-(TRIFLUOROMETHOXY)PHENYL]ACETAMIDO}PYRIDAZIN-3-YL)BUTYL]-1,3,4-THIADIAZOL-2-YL}ACETAMIDE; 2-Pyridineacetamide, N-(5-(4-(6-((2-(3-(trifluoromethoxy)phenyl)acetyl)amino)-3-pyridazinyl)butyl)-1,3,4-thiadiazol-2-yl)-; 2-Pyridineacetamide, N-[5-[4-[6-[[2-[3-(trifluoromethoxy)phenyl]acetyl]amino]-3-pyridazinyl]butyl]-1,3,4-thiadiazol-2-yl]-; 63J; Telaglenastat [USAN]; CB-839(Telaglenastat); Telaglenastat (USAN/INN); GTPL9053; CB-839 [WHO-DD]; CHEMBL3639788; SCHEMBL14987180; BDBM109086; HMS3741E19; HMS3873G13; AMY16835; BCP28287; EX-A1310; MFCD28167826; NSC783415; NSC795998; NSC798057; s7655; WHO 10815; AKOS025396175; ZINC169698697; CCG-270102; CS-3393; DB15232; NSC-783415; NSC-795998; NSC-798057; SB17221; NCGC00356145-11; 2-Pyridineacetamide, N-[5-[4-[6-[[2-[3-(trifluoromethoxy)phenyl]acetyl]amino]-3-pyridaz; AC-31603; AS-75090; CB839; CB 839 pound>>Telaglenastat,; DA-34988; HY-12248; FT-0767818; A14396; D11738; A857288; US8604016, 670; Q27075751; 2-Pyridineacetamide, N-[5-[4-[6-[[2-[3-(trifluoromethoxy)phenyl]acetyl]amino]-3-pyridazinyl]butyl]-1,3,4-thiadiazol-2-yl]-; N-[5-[4-[6-[[2-[3-(trifluoromethoxy)phenyl]acetyl]amino]-3-pyridazinyl]butyl]-1,3,4-thiadiazol-2-yl]-2-pyridineacetamide; N-[5-[4-[6-[[2-[3-(trifluoromethoxy)phenyl]acetyl]amino]-3-pyridazinyl]butyl]-1,3,4-thiadiazol-2-yl]-2-pyridineacetamide;CB-839; N-[6-(4-{5-[2-(pyridin-2-yl)acetamido]-1,3,4-thiadiazol-2-yl}butyl)pyridazin-3-yl]-2-[3-(trifluoromethoxy)phenyl]acetamide
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Status Phase 2 [1]
Structure
Formula
C26H24F3N7O3S
InChI
InChI=1S/C26H24F3N7O3S/c27-26(28,29)39-20-9-5-6-17(14-20)15-22(37)31-21-12-11-18(33-34-21)7-1-2-10-24-35-36-25(40-24)32-23(38)16-19-8-3-4-13-30-19/h3-6,8-9,11-14H,1-2,7,10,15-16H2,(H,31,34,37)(H,32,36,38)
InChIKey
PRAAPINBUWJLGA-UHFFFAOYSA-N
PubChem CID
71577426
DrugBank ID
DB15232
Full List of m6A Targets Related to This Drug
Cyclic AMP-dependent transcription factor ATF-4 (ATF4)
 Target Info 
In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Drug Response by This Target Gene [2]
Response Summary In colorectal cancer, Glutaminolysis inhibition upregulated ATF4 expression in an m6A-dependent manner to activate pro-survival autophagy through transcriptional activation of the mTOR inhibitor DDIT4. Determined the relationship between FTO alpha-ketoglutarate dependent dioxygenase (FTO), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), and ATF4. ATF4 transcriptionally upregulated DDIT4 to suppress Cyclic AMP-dependent transcription factor ATF-4 (ATF4), which induced pro-survival autophagy during glutaminolysis inhibition.
Responsed Disease Colorectal cancer ICD-11: 2B91
 Disease Info 
Target Regulator YTH domain-containing family protein 2 (YTHDF2) READER
 Regulator Info 
Target Regulation Down regulation
Pathway Response mTOR signaling pathway hsa04150
Cell Process RNA decay
Cell growth and death
Cell autophagy
In-vitro Model HCT 116 Colon carcinoma Homo sapiens CVCL_0291
SW480 Colon adenocarcinoma Homo sapiens CVCL_0546
Experiment 2 Reporting the m6A-centered Drug Response by This Target Gene [2]
Response Summary In colorectal cancer, Glutaminolysis inhibition upregulated ATF4 expression in an m6A-dependent manner to activate pro-survival autophagy through transcriptional activation of the mTOR inhibitor DDIT4. Determined the relationship between FTO alpha-ketoglutarate dependent dioxygenase (FTO), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), and ATF4. Cyclic AMP-dependent transcription factor ATF-4 (ATF4) transcriptionally upregulated DDIT4 to suppress mTOR, which induced pro-survival autophagy during glutaminolysis inhibition.
Responsed Disease Colorectal cancer ICD-11: 2B91
 Disease Info 
Target Regulator Fat mass and obesity-associated protein (FTO) ERASER
 Regulator Info 
Pathway Response mTOR signaling pathway hsa04150
Cell Process RNA decay
Cell growth and death
Cell autophagy
In-vitro Model HCT 116 Colon carcinoma Homo sapiens CVCL_0291
SW480 Colon adenocarcinoma Homo sapiens CVCL_0546
Serine/threonine-protein kinase mTOR (MTOR)
 Target Info 
In total 2 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Drug Response by This Target Gene [2]
Response Summary In colorectal cancer, Glutaminolysis inhibition upregulated ATF4 expression in an m6A-dependent manner to activate pro-survival autophagy through transcriptional activation of the mTOR inhibitor DDIT4. Determined the relationship between FTO alpha-ketoglutarate dependent dioxygenase (FTO), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), and ATF4. ATF4 transcriptionally upregulated DDIT4 to suppress Serine/threonine-protein kinase mTOR (MTOR), which induced pro-survival autophagy during glutaminolysis inhibition.
Responsed Disease Colorectal cancer ICD-11: 2B91
 Disease Info 
Target Regulator YTH domain-containing family protein 2 (YTHDF2) READER
 Regulator Info 
Target Regulation Up regulation
Pathway Response mTOR signaling pathway hsa04150
Autophagy hsa04140
Cell Process RNA decay
Cell growth and death
Cell autophagy
In-vitro Model HCT 116 Colon carcinoma Homo sapiens CVCL_0291
SW480 Colon adenocarcinoma Homo sapiens CVCL_0546
Experiment 2 Reporting the m6A-centered Drug Response by This Target Gene [2]
Response Summary In colorectal cancer, Glutaminolysis inhibition upregulated ATF4 expression in an m6A-dependent manner to activate pro-survival autophagy through transcriptional activation of the mTOR inhibitor DDIT4. Determined the relationship between FTO alpha-ketoglutarate dependent dioxygenase (FTO), YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), and ATF4. Serine/threonine-protein kinase mTOR (MTOR) transcriptionally upregulated DDIT4 to suppress mTOR, which induced pro-survival autophagy during glutaminolysis inhibition.
Responsed Disease Colorectal cancer ICD-11: 2B91
 Disease Info 
Target Regulator Fat mass and obesity-associated protein (FTO) ERASER
 Regulator Info 
Pathway Response mTOR signaling pathway hsa04150
Autophagy hsa04140
Cell Process RNA decay
Cell growth and death
Cell autophagy
In-vitro Model HCT 116 Colon carcinoma Homo sapiens CVCL_0291
SW480 Colon adenocarcinoma Homo sapiens CVCL_0546
Full List of Crosstalk(s) between m6A Modification and Epigenetic Regulation Related to This Drug
In total 4 item(s) under this drug
Crosstalk ID: M6ACROT03336
 Crosstalk Info 
m6A Regulator YTH domain-containing family protein 2 (YTHDF2)
 Regulator Info 
m6A Target Cyclic AMP-dependent transcription factor ATF-4 (ATF4)
 Target Gene 
Epigenetic Regulator Histone acetyltransferase p300 (P300)
Regulated Target Histone H3 lysine 18 lactylation (H3K18la)
Crosstalk relationship Histone modification → m6A
Disease Colorectal cancer
 Disease Info 
Crosstalk ID: M6ACROT03342
 Crosstalk Info 
m6A Regulator YTH domain-containing family protein 2 (YTHDF2)
 Regulator Info 
m6A Target Serine/threonine-protein kinase mTOR (MTOR)
 Target Gene 
Epigenetic Regulator Histone acetyltransferase p300 (P300)
Regulated Target Histone H3 lysine 18 lactylation (H3K18la)
Crosstalk relationship Histone modification → m6A
Disease Colorectal cancer
 Disease Info 
Crosstalk ID: M6ACROT03434
 Crosstalk Info 
m6A Regulator Fat mass and obesity-associated protein (FTO)
 Regulator Info 
m6A Target Cyclic AMP-dependent transcription factor ATF-4 (ATF4)
 Target Gene 
Epigenetic Regulator Histone deacetylase 1 (HDAC1)
Regulated Target Histone H3 lysine 27 acetylation (H3K27ac)
Crosstalk relationship Histone modification → m6A
Disease Colorectal cancer
 Disease Info 
Crosstalk ID: M6ACROT03440
 Crosstalk Info 
m6A Regulator Fat mass and obesity-associated protein (FTO)
 Regulator Info 
m6A Target Serine/threonine-protein kinase mTOR (MTOR)
 Target Gene 
Epigenetic Regulator Histone deacetylase 1 (HDAC1)
Regulated Target Histone H3 lysine 27 acetylation (H3K27ac)
Crosstalk relationship Histone modification → m6A
Disease Colorectal cancer
 Disease Info 
References
Ref 1 Testing Whether Cancers With Specific Mutations Respond Better to Glutaminase Inhibitor, Telaglenastat Hydrochloride, Anti-Cancer Treatment, BeGIN Study
Ref 2 Targeting ATF4-dependent pro-survival autophagy to synergize glutaminolysis inhibition. Theranostics. 2021 Jul 25;11(17):8464-8479. doi: 10.7150/thno.60028. eCollection 2021.