m6A-centered Drug Response Information

General Information of the Drug (ID: M6APDG01199)
Name
ABT-263
Synonyms
Navitoclax; ABT 263; S1001_Selleck; ABT263, Navitoclax; 4-(4-{[2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-N-({4-({(1R)-3-morpholin-4-yl-1-[(phenylsulfanyl)methyl]propyl}amino)-3-[(trifluoromethyl)sulfonyl]phenyl}sulfonyl)benzamide
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Status
Phase 3
Structure
3D MOL
2D MOL
Formula
C47H55ClF3N5O6S3
InChI
1S/C47H55ClF3N5O6S3/c1-46(2)20-18-42(34-8-12-37(48)13-9-34)36(31-46)32-55-22-24-56(25-23-55)39-14-10-35(11-15-39)45(57)53-65(60,61)41-16-17-43(44(30-41)64(58,59)47(49,50)51)52-38(19-21-54-26-28-62-29-27-54)33-63-40-6-4-3-5-7-40/h3-17,30,38,52H,18-29,31-33H2,1-2H3,(H,53,57)/t38-/m1/s1
InChIKey
JLYAXFNOILIKPP-KXQOOQHDSA-N
PubChem CID
24978538
TTD Drug ID
D06ETI
VARIDT Drug ID
DR01365
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.
Apoptosis regulator Bcl-2 (BCL-2)
Fat mass and obesity-associated protein (FTO)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Apoptosis regulator Bcl-2 (BCL-2) is a therapeutic target for ABT-263. The Fat mass and obesity-associated protein (FTO) has potential in affecting the response of ABT-263 through regulating the expression of Apoptosis regulator Bcl-2 (BCL-2). [1], [2]
Methyltransferase-like 14 (METTL14)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Apoptosis regulator Bcl-2 (BCL-2) is a therapeutic target for ABT-263. The Methyltransferase-like 14 (METTL14) has potential in affecting the response of ABT-263 through regulating the expression of Apoptosis regulator Bcl-2 (BCL-2). [2], [3]
Methyltransferase-like 3 (METTL3)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Apoptosis regulator Bcl-2 (BCL-2) is a therapeutic target for ABT-263. The Methyltransferase-like 3 (METTL3) has potential in affecting the response of ABT-263 through regulating the expression of Apoptosis regulator Bcl-2 (BCL-2). [2], [4]
RNA demethylase ALKBH5 (ALKBH5)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Apoptosis regulator Bcl-2 (BCL-2) is a therapeutic target for ABT-263. The RNA demethylase ALKBH5 (ALKBH5) has potential in affecting the response of ABT-263 through regulating the expression of Apoptosis regulator Bcl-2 (BCL-2). [2], [5]
YTH domain-containing family protein 1 (YTHDF1)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Apoptosis regulator Bcl-2 (BCL-2) is a therapeutic target for ABT-263. The YTH domain-containing family protein 1 (YTHDF1) has potential in affecting the response of ABT-263 through regulating the expression of Apoptosis regulator Bcl-2 (BCL-2). [2], [4]
YTH domain-containing family protein 2 (YTHDF2)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Apoptosis regulator Bcl-2 (BCL-2) is a therapeutic target for ABT-263. The YTH domain-containing family protein 2 (YTHDF2) has potential in affecting the response of ABT-263 through regulating the expression of Apoptosis regulator Bcl-2 (BCL-2). [2], [6]
G1/S-specific cyclin-D1 (CCND1)
Fat mass and obesity-associated protein (FTO)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary G1/S-specific cyclin-D1 (CCND1) is a therapeutic target for ABT-263. The Fat mass and obesity-associated protein (FTO) has potential in affecting the response of ABT-263 through regulating the expression of G1/S-specific cyclin-D1 (CCND1). [7], [8]
Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary G1/S-specific cyclin-D1 (CCND1) is a therapeutic target for ABT-263. The Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) has potential in affecting the response of ABT-263 through regulating the expression of G1/S-specific cyclin-D1 (CCND1). [8], [9]
Methyltransferase-like 16 (METTL16)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary G1/S-specific cyclin-D1 (CCND1) is a therapeutic target for ABT-263. The Methyltransferase-like 16 (METTL16) has potential in affecting the response of ABT-263 through regulating the expression of G1/S-specific cyclin-D1 (CCND1). [8], [10]
Methyltransferase-like 3 (METTL3)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary G1/S-specific cyclin-D1 (CCND1) is a therapeutic target for ABT-263. The Methyltransferase-like 3 (METTL3) has potential in affecting the response of ABT-263 through regulating the expression of G1/S-specific cyclin-D1 (CCND1). [8], [11]
Protein virilizer homolog (VIRMA)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary G1/S-specific cyclin-D1 (CCND1) is a therapeutic target for ABT-263. The Protein virilizer homolog (VIRMA) has potential in affecting the response of ABT-263 through regulating the expression of G1/S-specific cyclin-D1 (CCND1). [8], [9]
YTH domain-containing family protein 1 (YTHDF1)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary G1/S-specific cyclin-D1 (CCND1) is a therapeutic target for ABT-263. The YTH domain-containing family protein 1 (YTHDF1) has potential in affecting the response of ABT-263 through regulating the expression of G1/S-specific cyclin-D1 (CCND1). [8], [12]
YTH domain-containing family protein 2 (YTHDF2)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary G1/S-specific cyclin-D1 (CCND1) is a therapeutic target for ABT-263. The YTH domain-containing family protein 2 (YTHDF2) has potential in affecting the response of ABT-263 through regulating the expression of G1/S-specific cyclin-D1 (CCND1). [7], [8]
P-glycoprotein 1 (ABCB1)
Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary P-glycoprotein 1 (ABCB1) is a therapeutic target for ABT-263. The Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) has potential in affecting the response of ABT-263 through regulating the expression of P-glycoprotein 1 (ABCB1). [13], [14]
Methyltransferase-like 3 (METTL3)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary P-glycoprotein 1 (ABCB1) is a therapeutic target for ABT-263. The Methyltransferase-like 3 (METTL3) has potential in affecting the response of ABT-263 through regulating the expression of P-glycoprotein 1 (ABCB1). [14], [15]
References
Ref 1 The Complex Roles and Therapeutic Implications of m(6)A Modifications in Breast Cancer. Front Cell Dev Biol. 2021 Jan 11;8:615071. doi: 10.3389/fcell.2020.615071. eCollection 2020.
Ref 2 Emerging therapies for multiple myeloma. Expert Opin Emerg Drugs. 2009 Mar;14(1):99-127. doi: 10.1517/14728210802676278.
Ref 3 Methyltransferase-like 14 silencing relieves the development of atherosclerosis via m(6)A modification of p65 mRNA. Bioengineered. 2022 May;13(5):11832-11843. doi: 10.1080/21655979.2022.2031409.
Ref 4 Mettl3 inhibits the apoptosis and autophagy of chondrocytes in inflammation through mediating Bcl2 stability via Ythdf1-mediated m(6)A modification. Bone. 2022 Jan;154:116182. doi: 10.1016/j.bone.2021.116182. Epub 2021 Sep 13.
Ref 5 ALKBH5 inhibited autophagy of epithelial ovarian cancer through miR-7 and BCL-2. J Exp Clin Cancer Res. 2019 Apr 15;38(1):163. doi: 10.1186/s13046-019-1159-2.
Ref 6 A dynamic N(6)-methyladenosine methylome regulates intrinsic and acquired resistance to tyrosine kinase inhibitors. Cell Res. 2018 Nov;28(11):1062-1076. doi: 10.1038/s41422-018-0097-4. Epub 2018 Oct 8.
Ref 7 FTO regulates myoblast proliferation by controlling CCND1 expression in an m(6)A-YTHDF2-dependent manner. Exp Cell Res. 2021 Apr 15;401(2):112524. doi: 10.1016/j.yexcr.2021.112524. Epub 2021 Feb 27.
Ref 8 New selective nonsteroidal aromatase inhibitors: synthesis and inhibitory activity of 2,3 or 5-(alpha-azolylbenzyl)-1H-indoles. Bioorg Med Chem Lett. 1999 Feb 8;9(3):333-6. doi: 10.1016/s0960-894x(98)00737-9.
Ref 9 Identification of pathology-specific regulators of m(6)A RNA modification to optimize lung cancer management in the context of predictive, preventive, and personalized medicine. EPMA J. 2020 Jul 29;11(3):485-504. doi: 10.1007/s13167-020-00220-3. eCollection 2020 Sep.
Ref 10 METTL16 promotes cell proliferation by up-regulating cyclin D1 expression in gastric cancer. J Cell Mol Med. 2021 Jul;25(14):6602-6617. doi: 10.1111/jcmm.16664. Epub 2021 Jun 2.
Ref 11 METTL3 serves an oncogenic role in human ovarian cancer cells partially via the AKT signaling pathway. Oncol Lett. 2020 Apr;19(4):3197-3204. doi: 10.3892/ol.2020.11425. Epub 2020 Mar 3.
Ref 12 YTHDF1 links hypoxia adaptation and non-small cell lung cancer progression. Nat Commun. 2019 Oct 25;10(1):4892. doi: 10.1038/s41467-019-12801-6.
Ref 13 Binding of RNA m6A by IGF2BP3 triggers chemoresistance of HCT8 cells via upregulation of ABCB1. Am J Cancer Res. 2021 Apr 15;11(4):1428-1445. eCollection 2021.
Ref 14 The B-cell lymphoma 2 (BCL2)-inhibitors, ABT-737 and ABT-263, are substrates for P-glycoprotein. Biochem Biophys Res Commun. 2011 May 6;408(2):344-9.
Ref 15 METTL3 promotes adriamycin resistance in MCF-7 breast cancer cells by accelerating pri-microRNA-221-3p maturation in a m6A-dependent manner. Exp Mol Med. 2021 Jan;53(1):91-102. doi: 10.1038/s12276-020-00510-w. Epub 2021 Jan 8.