General Information of the Drug (ID: M6APDG02503)
Name
KW-2450
Status
Discontinued in Phase 1/2
Structure
3D MOL
Formula
C35H37N5O6S2
InChI
1S/C28H29N5O3S.C7H8O3S/c1-19-10-15-37-27(19)28(36)29-25-16-20(17-32-11-13-33(14-12-32)26(35)18-34)6-7-21(25)8-9-24-22-4-2-3-5-23(22)30-31-24;1-6-2-4-7(5-3-6)11(8,9)10/h2-10,15-16,34H,11-14,17-18H2,1H3,(H,29,36)(H,30,31);2-5H,1H3,(H,8,9,10)/b9-8+;
InChIKey
SIJKXSMUXNJNQM-HRNDJLQDSA-N
PubChem CID
56847547
TTD Drug ID
D0M3OR
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.
Insulin-like growth factor I receptor (IGF1R)
Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2)
In total 1 mechanisms lead to this potential drug response
Response Summary Insulin-like growth factor I receptor (IGF1R) is a therapeutic target for KW-2450. The Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) has potential in affecting the response of KW-2450 through regulating the expression of Insulin-like growth factor I receptor (IGF1R). [1], [2]
Methyltransferase-like 3 (METTL3)
In total 1 mechanisms lead to this potential drug response
Response Summary Insulin-like growth factor I receptor (IGF1R) is a therapeutic target for KW-2450. The Methyltransferase-like 3 (METTL3) has potential in affecting the response of KW-2450 through regulating the expression of Insulin-like growth factor I receptor (IGF1R). [2], [3]
RNA demethylase ALKBH5 (ALKBH5)
In total 1 mechanisms lead to this potential drug response
Response Summary Insulin-like growth factor I receptor (IGF1R) is a therapeutic target for KW-2450. The RNA demethylase ALKBH5 (ALKBH5) has potential in affecting the response of KW-2450 through regulating the expression of Insulin-like growth factor I receptor (IGF1R). [2], [4]
YTH domain-containing protein 2 (YTHDC2)
In total 1 mechanisms lead to this potential drug response
Response Summary Insulin-like growth factor I receptor (IGF1R) is a therapeutic target for KW-2450. The YTH domain-containing protein 2 (YTHDC2) has potential in affecting the response of KW-2450 through regulating the expression of Insulin-like growth factor I receptor (IGF1R). [2], [5]
References
Ref 1 IGF2BP2 promotes gastric cancer progression by regulating the IGF1R-RhoA-ROCK signaling pathway. Cell Signal. 2022 Jun;94:110313. doi: 10.1016/j.cellsig.2022.110313. Epub 2022 Mar 16.
Ref 2 Insulin-like growth factor-1 receptor inhibition induces a resistance mechanism via the epidermal growth factor receptor/HER3/AKT signaling pathway: rational basis for cotargeting insulin-like growth factor-1 receptor and epidermal growth factor receptor in hepatocellular carcinoma. Clin Cancer Res. 2009 Sep 1;15(17):5445-56. doi: 10.1158/1078-0432.CCR-08-2980. Epub 2009 Aug 25.
Ref 3 m(6) A modification of lncRNA PCAT6 promotes bone metastasis in prostate cancer through IGF2BP2-mediated IGF1R mRNA stabilization. Clin Transl Med. 2021 Jun;11(6):e426. doi: 10.1002/ctm2.426.
Ref 4 ALKBH5 regulates IGF1R expression to promote the Proliferation and Tumorigenicity of Endometrial Cancer. J Cancer. 2020 Jul 25;11(19):5612-5622. doi: 10.7150/jca.46097. eCollection 2020.
Ref 5 m(6)A Reader YTHDC2 Promotes Radiotherapy Resistance of Nasopharyngeal Carcinoma via Activating IGF1R/AKT/S6 Signaling Axis. Front Oncol. 2020 Jul 31;10:1166. doi: 10.3389/fonc.2020.01166. eCollection 2020.