m6A-centered Drug Response Information

General Information of the Drug (ID: M6APDG00576)
Name
Methotrexate
Synonyms
Metatrexan; Methotextrate; Methotrexat; Methotrexat-Ebewe; Methotrexate, L-; Methotrexatum; Methoxtrexate; Methylaminopterin; Methylaminopterinum; Metotressato [DCIT]; Metotrexato; Mexate; Mexate-Aq; N-Bismethylpteroylglutamic acid; A-Methopterin; A-Methpterin; Amethopterin; Amethopterin L-; Amethopterine; Antifolan; Emtexate; Folex-Pfs; L-Amethopterin; Maxtrex; Rasuvo; Rheumatrex; Trexall; methotrexate; (S)-2-(4-(((2,4-Diaminopteridin-6-yl)methyl)(methyl)amino)benzamido)pentanedioic acid; Abitrexate; Folex; Hdmtx; MTX; NCI-C04671
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Status
Approved
Structure
Formula
C20H22N8O5
InChI
1S/C20H22N8O5/c1-28(9-11-8-23-17-15(24-11)16(21)26-20(22)27-17)12-4-2-10(3-5-12)18(31)25-13(19(32)33)6-7-14(29)30/h2-5,8,13H,6-7,9H2,1H3,(H,25,31)(H,29,30)(H,32,33)(H4,21,22,23,26,27)/t13-/m0/s1
InChIKey
FBOZXECLQNJBKD-ZDUSSCGKSA-N
PubChem CID
126941
VARIDT Drug ID
DR00082
INTEDE Drug ID
DR1045
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.
Breast cancer resistance protein (ABCG2)
Methyltransferase-like 3 (METTL3)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Breast cancer resistance protein (ABCG2) is a therapeutic target for Methotrexate. The Methyltransferase-like 3 (METTL3) has potential in affecting the response of Methotrexate through regulating the expression of Breast cancer resistance protein (ABCG2). [1], [2]
Methylenetetrahydrofolate reductase (MTHFR)
Fat mass and obesity-associated protein (FTO)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Methylenetetrahydrofolate reductase (MTHFR) is a therapeutic target for Methotrexate. The Fat mass and obesity-associated protein (FTO) has potential in affecting the response of Methotrexate through regulating the expression of Methylenetetrahydrofolate reductase (MTHFR). [3], [4]
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 Methotrexate. The Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) has potential in affecting the response of Methotrexate through regulating the expression of P-glycoprotein 1 (ABCB1). [5], [6]
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 Methotrexate. The Methyltransferase-like 3 (METTL3) has potential in affecting the response of Methotrexate through regulating the expression of P-glycoprotein 1 (ABCB1). [1], [6]
References
Ref 1 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.
Ref 2 Wild-type breast cancer resistance protein (BCRP/ABCG2) is a methotrexate polyglutamate transporter. Cancer Res. 2003 Sep 1;63(17):5538-43.
Ref 3 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 4 The pharmacogenetics of methotrexate. Rheumatology (Oxford). 2007 Oct;46(10):1520-4. doi: 10.1093/rheumatology/kem147. Epub 2007 Jun 24.
Ref 5 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 6 Mammalian drug efflux transporters of the ATP binding cassette (ABC) family in multidrug resistance: A review of the past decade. Cancer Lett. 2016 Jan 1;370(1):153-64. doi: 10.1016/j.canlet.2015.10.010. Epub 2015 Oct 20.