m6A-centered Drug Response Information

General Information of the Drug (ID: M6APDG03332)
Name
AZD-2014
Synonyms
AZD2014; 1009298-59-2; Vistusertib; AZD-2014; AZD 2014; UNII-0BSC3P4H5X; 0BSC3P4H5X; cc-551; 3-[2,4-Bis((3S)-3-methylmorpholin-4-yl)pyrido[5,6-e]pyrimidin-7-yl]-N-methylbenzamide; CHEMBL2336325; 3-[2,4-Bis((3S)-3-methyLmorpholin-4-yl)pyrido-[5,6-e]pyrimidin-7-yl]-N-methylbenzamide; C25H30N6O3; 3-(2,4-bis((S)-3-methylmorpholino)pyrido[2,3-d]pyrimidin-7-yl)-N-methylbenzamide; 3-[2,4-bis[(3S)-3-methylmorpholin-4-yl]pyrido[2,3-d]pyrimidin-7-yl]-N-methylbenzamide; Vistusertib [INN]; Vistusertib [USAN]; Vistusertib (JAN/INN)
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Status
Phase 2
Structure
Formula
C25H30N6O3
InChI
1S/C25H30N6O3/c1-16-14-33-11-9-30(16)23-20-7-8-21(18-5-4-6-19(13-18)24(32)26-3)27-22(20)28-25(29-23)31-10-12-34-15-17(31)2/h4-8,13,16-17H,9-12,14-15H2,1-3H3,(H,26,32)/t16-,17-/m0/s1
InChIKey
JUSFANSTBFGBAF-IRXDYDNUSA-N
PubChem CID
25262792
TTD Drug ID
D0Z2UQ
INTEDE Drug ID
DR1837
Target Gene(s) and Their Upstream m6A Regulator, Together with the Effect of Target Gene(s) in Drug Response
The target genes involved in drug-target interaction (such as drug-metabolizing enzymes, drug transporters and therapeutic targets) and drug-mediated cell death signaling (including modulating DNA damage and repair capacity, escaping from drug-induced apoptosis, autophagy, cellular metabolic reprogramming, oncogenic bypass signaling, cell microenvironment, cell stemness, etc.) could be regulated by m6A regulator(s) and affected their corresponding drug response. You can browse detailed information on drug-related target gene(s) mediated by m6A regulators.
Cytochrome P450 2C8 (CYP2C8)
Fat mass and obesity-associated protein (FTO)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Cytochrome P450 2C8 (CYP2C8) is a therapeutic target for AZD-2014. The Fat mass and obesity-associated protein (FTO) has potential in affecting the response of AZD-2014 through regulating the expression of Cytochrome P450 2C8 (CYP2C8). [1], [2]
Methyltransferase-like 14 (METTL14)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Cytochrome P450 2C8 (CYP2C8) is a therapeutic target for AZD-2014. The Methyltransferase-like 14 (METTL14) has potential in affecting the response of AZD-2014 through regulating the expression of Cytochrome P450 2C8 (CYP2C8). [1], [2]
Methyltransferase-like 3 (METTL3)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Cytochrome P450 2C8 (CYP2C8) is a therapeutic target for AZD-2014. The Methyltransferase-like 3 (METTL3) has potential in affecting the response of AZD-2014 through regulating the expression of Cytochrome P450 2C8 (CYP2C8). [1], [2]
YTH domain-containing protein 2 (YTHDC2)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Cytochrome P450 2C8 (CYP2C8) is a therapeutic target for AZD-2014. The YTH domain-containing protein 2 (YTHDC2) has potential in affecting the response of AZD-2014 through regulating the expression of Cytochrome P450 2C8 (CYP2C8). [1], [2]
Mammalian target of rapamycin complex 1 (mTORC1)
Fat mass and obesity-associated protein (FTO)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Mammalian target of rapamycin complex 1 (mTORC1) is a therapeutic target for AZD-2014. The Fat mass and obesity-associated protein (FTO) has potential in affecting the response of AZD-2014 through regulating the expression of Mammalian target of rapamycin complex 1 (mTORC1). [3], [4]
Methyltransferase-like 14 (METTL14)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Mammalian target of rapamycin complex 1 (mTORC1) is a therapeutic target for AZD-2014. The Methyltransferase-like 14 (METTL14) has potential in affecting the response of AZD-2014 through regulating the expression of Mammalian target of rapamycin complex 1 (mTORC1). [4], [5]
Methyltransferase-like 3 (METTL3)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Mammalian target of rapamycin complex 1 (mTORC1) is a therapeutic target for AZD-2014. The Methyltransferase-like 3 (METTL3) has potential in affecting the response of AZD-2014 through regulating the expression of Mammalian target of rapamycin complex 1 (mTORC1). [4], [5]
RNA-binding motif protein 15 (RBM15)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Mammalian target of rapamycin complex 1 (mTORC1) is a therapeutic target for AZD-2014. The RNA-binding motif protein 15 (RBM15) has potential in affecting the response of AZD-2014 through regulating the expression of Mammalian target of rapamycin complex 1 (mTORC1). [4], [5]
RNA-binding motif protein 15B (RBM15B)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Mammalian target of rapamycin complex 1 (mTORC1) is a therapeutic target for AZD-2014. The RNA-binding motif protein 15B (RBM15B) has potential in affecting the response of AZD-2014 through regulating the expression of Mammalian target of rapamycin complex 1 (mTORC1). [4], [5]
Wilms tumor 1-associating protein (WTAP)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Mammalian target of rapamycin complex 1 (mTORC1) is a therapeutic target for AZD-2014. The Wilms tumor 1-associating protein (WTAP) has potential in affecting the response of AZD-2014 through regulating the expression of Mammalian target of rapamycin complex 1 (mTORC1). [4], [5]
Serine/threonine-protein kinase mTOR (mTOR)
Fat mass and obesity-associated protein (FTO)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Serine/threonine-protein kinase mTOR (mTOR) is a therapeutic target for AZD-2014. The Fat mass and obesity-associated protein (FTO) has potential in affecting the response of AZD-2014 through regulating the expression of Serine/threonine-protein kinase mTOR (mTOR). [6], [7]
Methyltransferase-like 14 (METTL14)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Serine/threonine-protein kinase mTOR (mTOR) is a therapeutic target for AZD-2014. The Methyltransferase-like 14 (METTL14) has potential in affecting the response of AZD-2014 through regulating the expression of Serine/threonine-protein kinase mTOR (mTOR). [7], [8]
Methyltransferase-like 3 (METTL3)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Serine/threonine-protein kinase mTOR (mTOR) is a therapeutic target for AZD-2014. The Methyltransferase-like 3 (METTL3) has potential in affecting the response of AZD-2014 through regulating the expression of Serine/threonine-protein kinase mTOR (mTOR). [7], [9]
YTH domain-containing family protein 1 (YTHDF1)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Serine/threonine-protein kinase mTOR (mTOR) is a therapeutic target for AZD-2014. The YTH domain-containing family protein 1 (YTHDF1) has potential in affecting the response of AZD-2014 through regulating the expression of Serine/threonine-protein kinase mTOR (mTOR). [7], [10]
YTH domain-containing family protein 2 (YTHDF2)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Serine/threonine-protein kinase mTOR (mTOR) is a therapeutic target for AZD-2014. The YTH domain-containing family protein 2 (YTHDF2) has potential in affecting the response of AZD-2014 through regulating the expression of Serine/threonine-protein kinase mTOR (mTOR). [6], [7]
Target of rapamycin complex 2 MAPKAP1 (MTORC2)
Methyltransferase-like 14 (METTL14)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Target of rapamycin complex 2 MAPKAP1 (MTORC2) is a therapeutic target for AZD-2014. The Methyltransferase-like 14 (METTL14) has potential in affecting the response of AZD-2014 through regulating the expression of Target of rapamycin complex 2 MAPKAP1 (MTORC2). [11], [12]
Methyltransferase-like 3 (METTL3)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Target of rapamycin complex 2 MAPKAP1 (MTORC2) is a therapeutic target for AZD-2014. The Methyltransferase-like 3 (METTL3) has potential in affecting the response of AZD-2014 through regulating the expression of Target of rapamycin complex 2 MAPKAP1 (MTORC2). [11], [12]
References
Ref 1 Methylation of adenosine at the N(6) position post-transcriptionally regulates hepatic P450s expression. Biochem Pharmacol. 2020 Jan;171:113697. doi: 10.1016/j.bcp.2019.113697. Epub 2019 Nov 7.
Ref 2 First-in-Human Pharmacokinetic and Pharmacodynamic Study of the Dual m-TORC 1/2 Inhibitor AZD2014. Clin Cancer Res. 2015 Aug 1;21(15):3412-9. doi: 10.1158/1078-0432.CCR-14-2422. Epub 2015 Mar 24.
Ref 3 Omeprazole improves chemosensitivity of gastric cancer cells by m6A demethylase FTO-mediated activation of mTORC1 and DDIT3 up-regulation. Biosci Rep. 2021 Jan 29;41(1):BSR20200842. doi: 10.1042/BSR20200842.
Ref 4 Constrained peptides' time to shine?. Nat Rev Drug Discov. 2018 Jul 30;17(8):531-533. doi: 10.1038/nrd.2018.125.
Ref 5 mTORC1-chaperonin CCT signaling regulates m(6)A RNA methylation to suppress autophagy. Proc Natl Acad Sci U S A. 2021 Mar 9;118(10):e2021945118. doi: 10.1073/pnas.2021945118.
Ref 6 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.
Ref 7 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: 2109).
Ref 8 The m6A methyltransferase METTL14 inhibits the proliferation, migration, and invasion of gastric cancer by regulating the PI3K/AKT/mTOR signaling pathway. J Clin Lab Anal. 2021 Mar;35(3):e23655. doi: 10.1002/jcla.23655. Epub 2020 Dec 12.
Ref 9 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 10 YTHDF1 promotes hepatocellular carcinoma progression via activating PI3K/AKT/mTOR signaling pathway and inducing epithelial-mesenchymal transition. Exp Hematol Oncol. 2021 Jun 4;10(1):35. doi: 10.1186/s40164-021-00227-0.
Ref 11 m(6)A mRNA methylation regulates AKT activity to promote the proliferation and tumorigenicity of endometrial cancer. Nat Cell Biol. 2018 Sep;20(9):1074-1083. doi: 10.1038/s41556-018-0174-4. Epub 2018 Aug 27.
Ref 12 How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.