m6A-centered Drug Response Information

General Information of the Drug (ID: M6APDG01471)
Name
WHI-P154
Status
Investigative
Structure
Formula
C16H14BrN3O3
InChI
1S/C16H14BrN3O3/c1-22-14-6-10-12(7-15(14)23-2)18-8-19-16(10)20-9-3-4-13(21)11(17)5-9/h3-8,21H,1-2H3,(H,18,19,20)
InChIKey
CBIAKDAYHRWZCU-UHFFFAOYSA-N
PubChem CID
3795
TTD Drug ID
D0E5IP
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.
Epidermal growth factor receptor (EGFR)
Methyltransferase-like 14 (METTL14)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Epidermal growth factor receptor (EGFR) is a therapeutic target for WHI-P154. The Methyltransferase-like 14 (METTL14) has potential in affecting the response of WHI-P154 through regulating the expression of Epidermal growth factor receptor (EGFR). [1], [2]
Methyltransferase-like 3 (METTL3)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Epidermal growth factor receptor (EGFR) is a therapeutic target for WHI-P154. The Methyltransferase-like 3 (METTL3) has potential in affecting the response of WHI-P154 through regulating the expression of Epidermal growth factor receptor (EGFR). [2], [3]
RNA demethylase ALKBH5 (ALKBH5)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Epidermal growth factor receptor (EGFR) is a therapeutic target for WHI-P154. The RNA demethylase ALKBH5 (ALKBH5) has potential in affecting the response of WHI-P154 through regulating the expression of Epidermal growth factor receptor (EGFR). [2], [4]
YTH domain-containing family protein 1 (YTHDF1)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Epidermal growth factor receptor (EGFR) is a therapeutic target for WHI-P154. The YTH domain-containing family protein 1 (YTHDF1) has potential in affecting the response of WHI-P154 through regulating the expression of Epidermal growth factor receptor (EGFR). [2], [5]
YTH domain-containing family protein 2 (YTHDF2)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Epidermal growth factor receptor (EGFR) is a therapeutic target for WHI-P154. The YTH domain-containing family protein 2 (YTHDF2) has potential in affecting the response of WHI-P154 through regulating the expression of Epidermal growth factor receptor (EGFR). [2], [6]
YTH domain-containing family protein 3 (YTHDF3)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Epidermal growth factor receptor (EGFR) is a therapeutic target for WHI-P154. The YTH domain-containing family protein 3 (YTHDF3) has potential in affecting the response of WHI-P154 through regulating the expression of Epidermal growth factor receptor (EGFR). [2], [7]
Janus kinase 2 (JAK-2)
Fat mass and obesity-associated protein (FTO)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Janus kinase 2 (JAK-2) is a therapeutic target for WHI-P154. The Fat mass and obesity-associated protein (FTO) has potential in affecting the response of WHI-P154 through regulating the expression of Janus kinase 2 (JAK-2). [8], [9]
Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Janus kinase 2 (JAK-2) is a therapeutic target for WHI-P154. The Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) has potential in affecting the response of WHI-P154 through regulating the expression of Janus kinase 2 (JAK-2). [9], [10]
Methyltransferase-like 3 (METTL3)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Janus kinase 2 (JAK-2) is a therapeutic target for WHI-P154. The Methyltransferase-like 3 (METTL3) has potential in affecting the response of WHI-P154 through regulating the expression of Janus kinase 2 (JAK-2). [9], [10]
RNA demethylase ALKBH5 (ALKBH5)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Janus kinase 2 (JAK-2) is a therapeutic target for WHI-P154. The RNA demethylase ALKBH5 (ALKBH5) has potential in affecting the response of WHI-P154 through regulating the expression of Janus kinase 2 (JAK-2). [9], [11]
Janus kinase 3 (JAK-3)
Wilms tumor 1-associating protein (WTAP)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Janus kinase 3 (JAK-3) is a therapeutic target for WHI-P154. The Wilms tumor 1-associating protein (WTAP) has potential in affecting the response of WHI-P154 through regulating the expression of Janus kinase 3 (JAK-3). [12], [13]
References
Ref 1 METTL14 Inhibits Hepatocellular Carcinoma Metastasis Through Regulating EGFR/PI3K/AKT Signaling Pathway in an m6A-Dependent Manner. Cancer Manag Res. 2020 Dec 23;12:13173-13184. doi: 10.2147/CMAR.S286275. eCollection 2020.
Ref 2 A systematic interaction map of validated kinase inhibitors with Ser/Thr kinases. Proc Natl Acad Sci U S A. 2007 Dec 18;104(51):20523-8. doi: 10.1073/pnas.0708800104. Epub 2007 Dec 11.
Ref 3 METTL3 induces PLX4032 resistance in melanoma by promoting m(6)A-dependent EGFR translation. Cancer Lett. 2021 Dec 1;522:44-56. doi: 10.1016/j.canlet.2021.09.015. Epub 2021 Sep 13.
Ref 4 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 5 Insufficient Radiofrequency Ablation Promotes Hepatocellular Carcinoma Metastasis Through N6-Methyladenosine mRNA Methylation-Dependent Mechanism. Hepatology. 2021 Sep;74(3):1339-1356. doi: 10.1002/hep.31766.
Ref 6 YTHDF2 suppresses cell proliferation and growth via destabilizing the EGFR mRNA in hepatocellular carcinoma. Cancer Lett. 2019 Feb 1;442:252-261. doi: 10.1016/j.canlet.2018.11.006. Epub 2018 Nov 10.
Ref 7 YTHDF3 Induces the Translation of m(6)A-Enriched Gene Transcripts to Promote Breast Cancer Brain Metastasis. Cancer Cell. 2020 Dec 14;38(6):857-871.e7. doi: 10.1016/j.ccell.2020.10.004. Epub 2020 Oct 29.
Ref 8 FTO inhibits UPR(mt)-induced apoptosis by activating JAK2/STAT3 pathway and reducing m6A level in adipocytes. Apoptosis. 2021 Aug;26(7-8):474-487. doi: 10.1007/s10495-021-01683-z. Epub 2021 Jul 1.
Ref 9 Discovery of 1-methyl-1H-imidazole derivatives as potent Jak2 inhibitors. J Med Chem. 2014 Jan 9;57(1):144-58. doi: 10.1021/jm401546n. Epub 2013 Dec 20.
Ref 10 N6-Methyladenosine Methyltransferase METTL3 Promotes Angiogenesis and Atherosclerosis by Upregulating the JAK2/STAT3 Pathway via m6A Reader IGF2BP1. Front Cell Dev Biol. 2021 Dec 7;9:731810. doi: 10.3389/fcell.2021.731810. eCollection 2021.
Ref 11 ALKBH5-HOXA10 loop-mediated JAK2 m6A demethylation and cisplatin resistance in epithelial ovarian cancer. J Exp Clin Cancer Res. 2021 Sep 8;40(1):284. doi: 10.1186/s13046-021-02088-1.
Ref 12 Transcriptome-Wide High-Throughput m6A Sequencing of Differential m6A Methylation Patterns in the Human Rheumatoid Arthritis Fibroblast-Like Synoviocytes Cell Line MH7A. J Inflamm Res. 2021 Feb 25;14:575-586. doi: 10.2147/JIR.S296006. eCollection 2021.
Ref 13 Naphthyl ketones: a new class of Janus kinase 3 inhibitors. Bioorg Med Chem Lett. 2000 Mar 20;10(6):575-9. doi: 10.1016/s0960-894x(00)00051-2.