m6A-centered Drug Response Information

General Information of the Drug (ID: M6APDG01116)
Name
RO-316233
Synonyms
119139-23-0; bisindolylmaleimide iv; 3,4-di(1H-indol-3-yl)-1H-pyrrole-2,5-dione; Arcyriarubin A; 3,4-Bis(3-indolyl)maleimide; 3,4-Di-1H-indol-3-yl-1H-pyrrole-2,5-dione; UNII-MBK3OO5K8T; BIM IV; 3,4-bis(1H-indol-3-yl)pyrrole-2,5-dione; MBK3OO5K8T; CHEMBL266487; 3,4-bis(1H-indol-3-yl)-2,5-dihydro-1H-pyrrole-2,5-dione; DQYBRTASHMYDJG-UHFFFAOYSA-N; 2,3-bis(1H-Indol-3-yl)maleimide; 1H-Pyrrole-2,5-dione, 3,4-di-1H-indol-3-yl-; Ro-31-6233; AK-15401; 3,4-bis(3-indolyl)-1H-pyrrole-2,5-dione; Bisindoylmaleimide; Bisindolyl deriv. 3
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Status
Investigative
Structure
Formula
C20H13N3O2
InChI
1S/C20H13N3O2/c24-19-17(13-9-21-15-7-3-1-5-11(13)15)18(20(25)23-19)14-10-22-16-8-4-2-6-12(14)16/h1-10,21-22H,(H,23,24,25)
InChIKey
DQYBRTASHMYDJG-UHFFFAOYSA-N
PubChem CID
2399
TTD Drug ID
D0L8HO
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.
cAMP-dependent protein kinase A type I (PRKAR1A)
Fat mass and obesity-associated protein (FTO)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary cAMP-dependent protein kinase A type I (PRKAR1A) is a therapeutic target for RO-316233. The Fat mass and obesity-associated protein (FTO) has potential in affecting the response of RO-316233 through regulating the expression of cAMP-dependent protein kinase A type I (PRKAR1A). [1], [2]
Cyclin-dependent kinase 1 (CDK1)
Methyltransferase-like 3 (METTL3)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Cyclin-dependent kinase 1 (CDK1) is a therapeutic target for RO-316233. The Methyltransferase-like 3 (METTL3) has potential in affecting the response of RO-316233 through regulating the expression of Cyclin-dependent kinase 1 (CDK1). [3], [4]
Protein virilizer homolog (VIRMA)
In total 1 mechanisms lead to this potential drug response
 Regulator Info 
Response Summary Cyclin-dependent kinase 1 (CDK1) is a therapeutic target for RO-316233. The Protein virilizer homolog (VIRMA) has potential in affecting the response of RO-316233 through regulating the expression of Cyclin-dependent kinase 1 (CDK1). [4], [5]
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-316233. The Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1) has potential in affecting the response of RO-316233 through regulating the expression of Extracellular signal-regulated kinase 2 (ERK2). [6], [7]
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-316233. The Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) has potential in affecting the response of RO-316233 through regulating the expression of Extracellular signal-regulated kinase 2 (ERK2). [7], [8]
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-316233. The YTH domain-containing family protein 3 (YTHDF3) has potential in affecting the response of RO-316233 through regulating the expression of Extracellular signal-regulated kinase 2 (ERK2). [7], [8]
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 RO-316233. The Fat mass and obesity-associated protein (FTO) has potential in affecting the response of RO-316233 through regulating the expression of NAD-dependent deacetylase sirtuin-1 (SIRT1). [9], [10]
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 RO-316233. The Methyltransferase-like 14 (METTL14) has potential in affecting the response of RO-316233 through regulating the expression of NAD-dependent deacetylase sirtuin-1 (SIRT1). [10], [11]
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 RO-316233. The Methyltransferase-like 3 (METTL3) has potential in affecting the response of RO-316233 through regulating the expression of NAD-dependent deacetylase sirtuin-1 (SIRT1). [10], [12]
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 RO-316233. The Protein virilizer homolog (VIRMA) has potential in affecting the response of RO-316233 through regulating the expression of NAD-dependent deacetylase sirtuin-1 (SIRT1). [10], [13]
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 RO-316233. The Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1) has potential in affecting the response of RO-316233 through regulating the expression of RAC-alpha serine/threonine-protein kinase (AKT1). [7], [14]
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 RO-316233. The Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) has potential in affecting the response of RO-316233 through regulating the expression of RAC-alpha serine/threonine-protein kinase (AKT1). [7], [8]
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 RO-316233. The Methyltransferase-like 14 (METTL14) has potential in affecting the response of RO-316233 through regulating the expression of RAC-alpha serine/threonine-protein kinase (AKT1). [7], [15]
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 RO-316233. The Methyltransferase-like 3 (METTL3) has potential in affecting the response of RO-316233 through regulating the expression of RAC-alpha serine/threonine-protein kinase (AKT1). [7], [16]
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 RO-316233. The RNA demethylase ALKBH5 (ALKBH5) has potential in affecting the response of RO-316233 through regulating the expression of RAC-alpha serine/threonine-protein kinase (AKT1). [7], [17]
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 RO-316233. The YTH domain-containing family protein 1 (YTHDF1) has potential in affecting the response of RO-316233 through regulating the expression of RAC-alpha serine/threonine-protein kinase (AKT1). [7], [18]
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 RO-316233. The YTH domain-containing family protein 2 (YTHDF2) has potential in affecting the response of RO-316233 through regulating the expression of RAC-alpha serine/threonine-protein kinase (AKT1). [7], [19]
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 RO-316233. The YTH domain-containing family protein 3 (YTHDF3) has potential in affecting the response of RO-316233 through regulating the expression of RAC-alpha serine/threonine-protein kinase (AKT1). [7], [8]
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 RO-316233. The YTH domain-containing protein 2 (YTHDC2) has potential in affecting the response of RO-316233 through regulating the expression of RAC-alpha serine/threonine-protein kinase (AKT1). [7], [20]
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 RO-316233. The Methyltransferase-like 3 (METTL3) has potential in affecting the response of RO-316233 through regulating the expression of Ribosomal protein S6 kinase beta-1 (S6K1). [7], [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 RO-316233. The Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) has potential in affecting the response of RO-316233 through regulating the expression of Stress-activated protein kinase 2a (p38 alpha). [8], [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 RO-316233. The Methyltransferase-like 3 (METTL3) has potential in affecting the response of RO-316233 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 RO-316233. The YTH domain-containing family protein 3 (YTHDF3) has potential in affecting the response of RO-316233 through regulating the expression of Stress-activated protein kinase 2a (p38 alpha). [8], [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 RO-316233. The Methyltransferase-like 3 (METTL3) has potential in affecting the response of RO-316233 through regulating the expression of Stress-activated protein kinase JNK1 (JNK1). [7], [24]
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 RO-316233. The RNA demethylase ALKBH5 (ALKBH5) has potential in affecting the response of RO-316233 through regulating the expression of Stress-activated protein kinase JNK1 (JNK1). [7], [25]
References
Ref 1 FTO-Dependent N (6)-Methyladenosine Modifications Inhibit Ovarian Cancer Stem Cell Self-Renewal by Blocking cAMP Signaling. Cancer Res. 2020 Aug 15;80(16):3200-3214. doi: 10.1158/0008-5472.CAN-19-4044. Epub 2020 Jun 30.
Ref 2 Liquid-phase synthesis of a pegylated adenosine-oligoarginine conjugate, cell-permeable inhibitor of cAMP-dependent protein kinase. Bioorg Med Chem Lett. 2003 Sep 15;13(18):3035-9. doi: 10.1016/s0960-894x(03)00641-3.
Ref 3 CircMETTL3, upregulated in a m6A-dependent manner, promotes breast cancer progression. Int J Biol Sci. 2021 Mar 15;17(5):1178-1190. doi: 10.7150/ijbs.57783. eCollection 2021.
Ref 4 Design of new inhibitors for cdc2 kinase based on a multiple pseudosubstrate structure. Bioorg Med Chem Lett. 1998 May 5;8(9):1019-22. doi: 10.1016/s0960-894x(98)00163-2.
Ref 5 KIAA1429 acts as an oncogenic factor in breast cancer by regulating CDK1 in an N6-methyladenosine-independent manner. Oncogene. 2019 Aug;38(33):6123-6141. doi: 10.1038/s41388-019-0861-z. Epub 2019 Jul 8.
Ref 6 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 7 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 8 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 9 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 10 Adenosine mimetics as inhibitors of NAD+-dependent histone deacetylases, from kinase to sirtuin inhibition. J Med Chem. 2006 Dec 14;49(25):7307-16. doi: 10.1021/jm060118b.
Ref 11 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 12 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 13 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 14 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 15 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 16 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 17 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 18 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 19 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 20 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 21 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 22 Synthesis and biological testing of purine derivatives as potential ATP-competitive kinase inhibitors. J Med Chem. 2005 Feb 10;48(3):710-22. doi: 10.1021/jm0408767.
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 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.