m6A-centered Drug Response Information

General Information of the Drug (ID: M6APDG02191)
Name
Ro31-8220
Synonyms
Bisindolylmaleimide IX; ro 31-8220; bisindolylmaleimide IX; 125314-64-9; Ro 31 8220; Ro 318220; UNII-W9A0B5E78O; Ro-318220; Ro-31-8220; CHEMBL6291; W9A0B5E78O; CHEBI:38912; 3-{3-[4-(1-methyl-1H-indol-3-yl)-2,5-dioxo-2,5-dihydro-1H-pyrrol-3-yl]-1H-indol-1-yl}propyl carbamimidothioate; Ro 31-8220 ; 3-{3-[4-(1-methyl-1H-indol-3-yl)-2,5-dioxo-2,5-dihydro-1H-pyrrol-3-yl]-1H-indol-1-yl}propyl imidothiocarbamate; CHEMBL1591531; Carbamimidothioic acid, 3-(3-(2,5-dihydro-4-(1-methyl-1H-indol-3-yl)-2,5-dioxo-1H-pyrrol-3-yl)-1H-indol-1-yl)propyl; Ro 318220; bisindolymaleimide IX; BISINDOLYLMALEIMIDE IX
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Status
Investigative
Structure
Formula
C25H23N5O2S
InChI
1S/C25H23N5O2S/c1-29-13-17(15-7-2-4-9-19(15)29)21-22(24(32)28-23(21)31)18-14-30(11-6-12-33-25(26)27)20-10-5-3-8-16(18)20/h2-5,7-10,13-14H,6,11-12H2,1H3,(H3,26,27)(H,28,31,32)
InChIKey
DSXXEELGXBCYNQ-UHFFFAOYSA-N
PubChem CID
5083
TTD Drug ID
D0M5FF
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.
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 Ro31-8220. The Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1) has potential in affecting the response of Ro31-8220 through regulating the expression of Extracellular signal-regulated kinase 2 (ERK2). [1], [2]
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 Ro31-8220. The Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) has potential in affecting the response of Ro31-8220 through regulating the expression of Extracellular signal-regulated kinase 2 (ERK2). [2], [3]
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 Ro31-8220. The YTH domain-containing family protein 3 (YTHDF3) has potential in affecting the response of Ro31-8220 through regulating the expression of Extracellular signal-regulated kinase 2 (ERK2). [2], [3]
Glycogen synthase kinase-3 beta (GSK-3B)
Fat mass and obesity-associated protein (FTO)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Glycogen synthase kinase-3 beta (GSK-3B) is a therapeutic target for Ro31-8220. The Fat mass and obesity-associated protein (FTO) has potential in affecting the response of Ro31-8220 through regulating the expression of Glycogen synthase kinase-3 beta (GSK-3B). [4], [5]
Methyltransferase-like 14 (METTL14)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Glycogen synthase kinase-3 beta (GSK-3B) is a therapeutic target for Ro31-8220. The Methyltransferase-like 14 (METTL14) has potential in affecting the response of Ro31-8220 through regulating the expression of Glycogen synthase kinase-3 beta (GSK-3B). [5], [6]
NAD-dependent deacetylase sirtuin-1 (SIRT1)
Fat mass and obesity-associated protein (FTO)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary NAD-dependent deacetylase sirtuin-1 (SIRT1) is a therapeutic target for Ro31-8220. The Fat mass and obesity-associated protein (FTO) has potential in affecting the response of Ro31-8220 through regulating the expression of NAD-dependent deacetylase sirtuin-1 (SIRT1). [7], [8]
Methyltransferase-like 14 (METTL14)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary NAD-dependent deacetylase sirtuin-1 (SIRT1) is a therapeutic target for Ro31-8220. The Methyltransferase-like 14 (METTL14) has potential in affecting the response of Ro31-8220 through regulating the expression of NAD-dependent deacetylase sirtuin-1 (SIRT1). [8], [9]
Methyltransferase-like 3 (METTL3)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary NAD-dependent deacetylase sirtuin-1 (SIRT1) is a therapeutic target for Ro31-8220. The Methyltransferase-like 3 (METTL3) has potential in affecting the response of Ro31-8220 through regulating the expression of NAD-dependent deacetylase sirtuin-1 (SIRT1). [8], [10]
Protein virilizer homolog (VIRMA)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary NAD-dependent deacetylase sirtuin-1 (SIRT1) is a therapeutic target for Ro31-8220. The Protein virilizer homolog (VIRMA) has potential in affecting the response of Ro31-8220 through regulating the expression of NAD-dependent deacetylase sirtuin-1 (SIRT1). [8], [11]
RAC-alpha serine/threonine-protein kinase (AKT1)
Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary RAC-alpha serine/threonine-protein kinase (AKT1) is a therapeutic target for Ro31-8220. The Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1) has potential in affecting the response of Ro31-8220 through regulating the expression of RAC-alpha serine/threonine-protein kinase (AKT1). [12], [13]
Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary RAC-alpha serine/threonine-protein kinase (AKT1) is a therapeutic target for Ro31-8220. The Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) has potential in affecting the response of Ro31-8220 through regulating the expression of RAC-alpha serine/threonine-protein kinase (AKT1). [3], [13]
Methyltransferase-like 14 (METTL14)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary RAC-alpha serine/threonine-protein kinase (AKT1) is a therapeutic target for Ro31-8220. The Methyltransferase-like 14 (METTL14) has potential in affecting the response of Ro31-8220 through regulating the expression of RAC-alpha serine/threonine-protein kinase (AKT1). [13], [14]
Methyltransferase-like 3 (METTL3)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary RAC-alpha serine/threonine-protein kinase (AKT1) is a therapeutic target for Ro31-8220. The Methyltransferase-like 3 (METTL3) has potential in affecting the response of Ro31-8220 through regulating the expression of RAC-alpha serine/threonine-protein kinase (AKT1). [13], [15]
RNA demethylase ALKBH5 (ALKBH5)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary RAC-alpha serine/threonine-protein kinase (AKT1) is a therapeutic target for Ro31-8220. The RNA demethylase ALKBH5 (ALKBH5) has potential in affecting the response of Ro31-8220 through regulating the expression of RAC-alpha serine/threonine-protein kinase (AKT1). [13], [16]
YTH domain-containing family protein 1 (YTHDF1)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary RAC-alpha serine/threonine-protein kinase (AKT1) is a therapeutic target for Ro31-8220. The YTH domain-containing family protein 1 (YTHDF1) has potential in affecting the response of Ro31-8220 through regulating the expression of RAC-alpha serine/threonine-protein kinase (AKT1). [13], [17]
YTH domain-containing family protein 2 (YTHDF2)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary RAC-alpha serine/threonine-protein kinase (AKT1) is a therapeutic target for Ro31-8220. The YTH domain-containing family protein 2 (YTHDF2) has potential in affecting the response of Ro31-8220 through regulating the expression of RAC-alpha serine/threonine-protein kinase (AKT1). [13], [18]
YTH domain-containing family protein 3 (YTHDF3)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary RAC-alpha serine/threonine-protein kinase (AKT1) is a therapeutic target for Ro31-8220. The YTH domain-containing family protein 3 (YTHDF3) has potential in affecting the response of Ro31-8220 through regulating the expression of RAC-alpha serine/threonine-protein kinase (AKT1). [3], [13]
YTH domain-containing protein 2 (YTHDC2)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary RAC-alpha serine/threonine-protein kinase (AKT1) is a therapeutic target for Ro31-8220. The YTH domain-containing protein 2 (YTHDC2) has potential in affecting the response of Ro31-8220 through regulating the expression of RAC-alpha serine/threonine-protein kinase (AKT1). [13], [19]
Ribosomal protein S6 kinase beta-1 (S6K1)
Methyltransferase-like 3 (METTL3)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Ribosomal protein S6 kinase beta-1 (S6K1) is a therapeutic target for Ro31-8220. The Methyltransferase-like 3 (METTL3) has potential in affecting the response of Ro31-8220 through regulating the expression of Ribosomal protein S6 kinase beta-1 (S6K1). [20], [21]
Stress-activated protein kinase 2a (p38 alpha)
Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Stress-activated protein kinase 2a (p38 alpha) is a therapeutic target for Ro31-8220. The Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) has potential in affecting the response of Ro31-8220 through regulating the expression of Stress-activated protein kinase 2a (p38 alpha). [3], [22]
Methyltransferase-like 3 (METTL3)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Stress-activated protein kinase 2a (p38 alpha) is a therapeutic target for Ro31-8220. The Methyltransferase-like 3 (METTL3) has potential in affecting the response of Ro31-8220 through regulating the expression of Stress-activated protein kinase 2a (p38 alpha). [22], [23]
YTH domain-containing family protein 3 (YTHDF3)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Stress-activated protein kinase 2a (p38 alpha) is a therapeutic target for Ro31-8220. The YTH domain-containing family protein 3 (YTHDF3) has potential in affecting the response of Ro31-8220 through regulating the expression of Stress-activated protein kinase 2a (p38 alpha). [3], [22]
Stress-activated protein kinase JNK1 (JNK1)
Methyltransferase-like 3 (METTL3)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Stress-activated protein kinase JNK1 (JNK1) is a therapeutic target for Ro31-8220. The Methyltransferase-like 3 (METTL3) has potential in affecting the response of Ro31-8220 through regulating the expression of Stress-activated protein kinase JNK1 (JNK1). [24], [25]
RNA demethylase ALKBH5 (ALKBH5)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Stress-activated protein kinase JNK1 (JNK1) is a therapeutic target for Ro31-8220. The RNA demethylase ALKBH5 (ALKBH5) has potential in affecting the response of Ro31-8220 through regulating the expression of Stress-activated protein kinase JNK1 (JNK1). [25], [26]
References
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Ref 2 Biological evaluation of a multi-targeted small molecule inhibitor of tumor-induced angiogenesis. Bioorg Med Chem Lett. 2006 Apr 1;16(7):1950-3. doi: 10.1016/j.bmcl.2005.12.092. Epub 2006 Feb 3.
Ref 3 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 4 Vascular Smooth Muscle FTO Promotes Aortic Dissecting Aneurysms via m6A Modification of Klf5. Front Cardiovasc Med. 2020 Nov 20;7:592550. doi: 10.3389/fcvm.2020.592550. eCollection 2020.
Ref 5 Identification of ellagic acid as potent inhibitor of protein kinase CK2: a successful example of a virtual screening application. J Med Chem. 2006 Apr 20;49(8):2363-6. doi: 10.1021/jm060112m.
Ref 6 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 7 SIRT1 Regulates N(6) -Methyladenosine RNA Modification in Hepatocarcinogenesis by Inducing RANBP2-Dependent FTO SUMOylation. Hepatology. 2020 Dec;72(6):2029-2050. doi: 10.1002/hep.31222. Epub 2020 Oct 22.
Ref 8 Characterization of sirtuin inhibitors in nematodes expressing a muscular dystrophy protein reveals muscle cell and behavioral protection by specific sirtinol analogues. J Med Chem. 2010 Feb 11;53(3):1407-11. doi: 10.1021/jm9013345.
Ref 9 METTL14 aggravates podocyte injury and glomerulopathy progression through N(6)-methyladenosine-dependent downregulating of Sirt1. Cell Death Dis. 2021 Sep 27;12(10):881. doi: 10.1038/s41419-021-04156-y.
Ref 10 METTL3 inhibits hepatic insulin sensitivity via N6-methyladenosine modification of Fasn mRNA and promoting fatty acid metabolism. Biochem Biophys Res Commun. 2019 Oct 8;518(1):120-126. doi: 10.1016/j.bbrc.2019.08.018. Epub 2019 Aug 10.
Ref 11 m(6)A methyltransferase KIAA1429 acts as an oncogenic factor in colorectal cancer by regulating SIRT1 in an m(6)A-dependent manner. Cell Death Discov. 2022 Feb 25;8(1):83. doi: 10.1038/s41420-022-00878-w.
Ref 12 HNRNPA2B1 regulates tamoxifen- and fulvestrant-sensitivity and hallmarks of endocrine resistance in breast cancer cells. Cancer Lett. 2021 Oct 10;518:152-168. doi: 10.1016/j.canlet.2021.07.015. Epub 2021 Jul 14.
Ref 13 A phthalide with in vitro growth inhibitory activity from an oidiodendron strain. J Nat Prod. 2004 Dec;67(12):2086-9. doi: 10.1021/np040123n.
Ref 14 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 15 Methyltransferase-like 3 promotes the progression of lung cancer via activating PI3K/AKT/mTOR pathway. Clin Exp Pharmacol Physiol. 2022 Jul;49(7):748-758. doi: 10.1111/1440-1681.13647. Epub 2022 May 23.
Ref 16 ALKBH5-mediated m(6)A demethylation of KCNK15-AS1 inhibits pancreatic cancer progression via regulating KCNK15 and PTEN/AKT signaling. Cell Death Dis. 2021 Dec 1;12(12):1121. doi: 10.1038/s41419-021-04401-4.
Ref 17 YTHDF1 promotes hepatocellular carcinoma progression via activating PI3K/AKT/mTOR signaling pathway and inducing epithelial-mesenchymal transition. Exp Hematol Oncol. 2021 Jun 4;10(1):35. doi: 10.1186/s40164-021-00227-0.
Ref 18 YTHDF2 mediates the mRNA degradation of the tumor suppressors to induce AKT phosphorylation in N6-methyladenosine-dependent way in prostate cancer. Mol Cancer. 2020 Oct 29;19(1):152. doi: 10.1186/s12943-020-01267-6.
Ref 19 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.
Ref 20 m(6)A methyltransferase METTL3 promotes retinoblastoma progression via PI3K/AKT/mTOR pathway. J Cell Mol Med. 2020 Oct 8;24(21):12368-78. doi: 10.1111/jcmm.15736. Online ahead of print.
Ref 21 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 22 Structure-activity relationships of 6-(2,6-dichlorophenyl)-8-methyl-2-(phenylamino)pyrido[2,3-d]pyrimidin-7-ones: toward selective Abl inhibitors. Bioorg Med Chem Lett. 2009 Dec 15;19(24):6872-6. doi: 10.1016/j.bmcl.2009.10.085. Epub 2009 Oct 23.
Ref 23 m(6)A methyltransferase METTL3 suppresses colorectal cancer proliferation and migration through p38/ERK pathways. Onco Targets Ther. 2019 Jun 4;12:4391-4402. doi: 10.2147/OTT.S201052. eCollection 2019.
Ref 24 METTL3 regulates alternative splicing of MyD88 upon the lipopolysaccharide-induced inflammatory response in human dental pulp cells. J Cell Mol Med. 2018 May;22(5):2558-2568. doi: 10.1111/jcmm.13491. Epub 2018 Mar 4.
Ref 25 The selectivity of protein kinase inhibitors: a further update. Biochem J. 2007 Dec 15;408(3):297-315. doi: 10.1042/BJ20070797.
Ref 26 Post-translational modification of RNA m6A demethylase ALKBH5 regulates ROS-induced DNA damage response. Nucleic Acids Res. 2021 Jun 4;49(10):5779-5797. doi: 10.1093/nar/gkab415.