m6A-centered Drug Response Information

General Information of the Drug (ID: M6APDG00309)
Name
Ro-4396686
Synonyms
SCHEMBL5809947; CHEMBL606964
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Status
Investigative
Structure
Formula
C24H24FN5O3
InChI
1S/C24H24FN5O3/c1-33-21-10-7-18(8-11-21)29-14-15-13-26-23(27-17-4-2-16(25)3-5-17)28-22(15)30(24(29)32)19-6-9-20(31)12-19/h2-5,7-8,10-11,13,19-20,31H,6,9,12,14H2,1H3,(H,26,27,28)/t19-,20-/m1/s1
InChIKey
KXEMINRANVTICS-WOJBJXKFSA-N
PubChem CID
11396738
TTD Drug ID
D09XIL
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 Ro-4396686. The Methyltransferase-like 14 (METTL14) has potential in affecting the response of Ro-4396686 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 Ro-4396686. The Methyltransferase-like 3 (METTL3) has potential in affecting the response of Ro-4396686 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 Ro-4396686. The RNA demethylase ALKBH5 (ALKBH5) has potential in affecting the response of Ro-4396686 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 Ro-4396686. The YTH domain-containing family protein 1 (YTHDF1) has potential in affecting the response of Ro-4396686 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 Ro-4396686. The YTH domain-containing family protein 2 (YTHDF2) has potential in affecting the response of Ro-4396686 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 Ro-4396686. The YTH domain-containing family protein 3 (YTHDF3) has potential in affecting the response of Ro-4396686 through regulating the expression of Epidermal growth factor receptor (EGFR). [2], [7]
Extracellular signal-regulated kinase 2 (ERK2)
Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Extracellular signal-regulated kinase 2 (ERK2) is a therapeutic target for Ro-4396686. The Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1) has potential in affecting the response of Ro-4396686 through regulating the expression of Extracellular signal-regulated kinase 2 (ERK2). [8], [9]
Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Extracellular signal-regulated kinase 2 (ERK2) is a therapeutic target for Ro-4396686. The Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) has potential in affecting the response of Ro-4396686 through regulating the expression of Extracellular signal-regulated kinase 2 (ERK2). [9], [10]
YTH domain-containing family protein 3 (YTHDF3)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Extracellular signal-regulated kinase 2 (ERK2) is a therapeutic target for Ro-4396686. The YTH domain-containing family protein 3 (YTHDF3) has potential in affecting the response of Ro-4396686 through regulating the expression of Extracellular signal-regulated kinase 2 (ERK2). [9], [10]
Fibroblast growth factor receptor 4 (FGFR4)
Methyltransferase-like 14 (METTL14)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Fibroblast growth factor receptor 4 (FGFR4) is a therapeutic target for Ro-4396686. The Methyltransferase-like 14 (METTL14) has potential in affecting the response of Ro-4396686 through regulating the expression of Fibroblast growth factor receptor 4 (FGFR4). [11], [12]
Fyn tyrosine protein kinase (FYN)
YTH domain-containing family protein 2 (YTHDF2)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Fyn tyrosine protein kinase (FYN) is a therapeutic target for Ro-4396686. The YTH domain-containing family protein 2 (YTHDF2) has potential in affecting the response of Ro-4396686 through regulating the expression of Fyn tyrosine protein kinase (FYN). [13], [14]
Platelet-derived growth factor receptor alpha (PDGFRA)
Methyltransferase-like 3 (METTL3)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Platelet-derived growth factor receptor alpha (PDGFRA) is a therapeutic target for Ro-4396686. The Methyltransferase-like 3 (METTL3) has potential in affecting the response of Ro-4396686 through regulating the expression of Platelet-derived growth factor receptor alpha (PDGFRA). [15], [16]
Platelet-derived growth factor receptor beta (PDGFRB)
Fat mass and obesity-associated protein (FTO)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Platelet-derived growth factor receptor beta (PDGFRB) is a therapeutic target for Ro-4396686. The Fat mass and obesity-associated protein (FTO) has potential in affecting the response of Ro-4396686 through regulating the expression of Platelet-derived growth factor receptor beta (PDGFRB). [16], [17]
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 Design, synthesis, and biological evaluation of 3,4-diarylmaleimides as angiogenesis inhibitors. J Med Chem. 2006 Feb 23;49(4):1271-81. doi: 10.1021/jm0580297.
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 hnRNPA2B1 Promotes Colon Cancer Progression via the MAPK Pathway. Front Genet. 2021 Sep 22;12:666451. doi: 10.3389/fgene.2021.666451. eCollection 2021.
Ref 9 Specificity and mechanism of action of some commonly used protein kinase inhibitors. Biochem J. 2000 Oct 1;351(Pt 1):95-105. doi: 10.1042/0264-6021:3510095.
Ref 10 N6-methyladenosine reader YTH N6-methyladenosine RNA binding protein 3 or insulin like growth factor 2 mRNA binding protein 2 knockdown protects human bronchial epithelial cells from hypoxia/reoxygenation injury by inactivating p38 MAPK, AKT, ERK1/2, and NF-KappaB pathways. Bioengineered. 2022 May;13(5):11973-11986. doi: 10.1080/21655979.2021.1999550.
Ref 11 N6-methyladenosine regulated FGFR4 attenuates ferroptotic cell death in recalcitrant HER2-positive breast cancer. Nat Commun. 2022 May 13;13(1):2672. doi: 10.1038/s41467-022-30217-7.
Ref 12 Pyrido[2,3-d]pyrimidin-7-one inhibitors of cyclin-dependent kinases. J Med Chem. 2000 Nov 30;43(24):4606-16. doi: 10.1021/jm000271k.
Ref 13 PA2G4 promotes the metastasis of hepatocellular carcinoma by stabilizing FYN mRNA in a YTHDF2-dependent manner. Cell Biosci. 2022 May 7;12(1):55. doi: 10.1186/s13578-022-00788-5.
Ref 14 Mixed-lineage kinase 1 and mixed-lineage kinase 3 subtype-selective dihydronaphthyl[3,4-a]pyrrolo[3,4-c]carbazole-5-ones: optimization, mixed-lineage kinase 1 crystallography, and oral in vivo activity in 1-methyl-4-phenyltetrahydropyridine models. J Med Chem. 2008 Sep 25;51(18):5680-9. doi: 10.1021/jm8005838. Epub 2008 Aug 21.
Ref 15 METTL3-mediated N (6)-methyladenosine modification governs pericyte dysfunction during diabetes-induced retinal vascular complication. Theranostics. 2022 Jan 1;12(1):277-289. doi: 10.7150/thno.63441. eCollection 2022.
Ref 16 Biochemical and cellular effects of c-Src kinase-selective pyrido[2, 3-d]pyrimidine tyrosine kinase inhibitors. Biochem Pharmacol. 2000 Oct 1;60(7):885-98. doi: 10.1016/s0006-2952(00)00405-6.
Ref 17 Mutant NPM1-Regulated FTO-Mediated m(6)A Demethylation Promotes Leukemic Cell Survival via PDGFRB/ERK Signaling Axis. Front Oncol. 2022 Feb 8;12:817584. doi: 10.3389/fonc.2022.817584. eCollection 2022.