Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DMK3SAF)

• Drug Name: BI-D1870 Drug Info
• Synonyms: 501437-28-1; 2-((3,5-difluoro-4-hydroxyphenyl)amino)-8-isopentyl-5,7-dimethyl-7,8-dihydropteridin-6(5H)-one; 2-(3,5-difluoro-4-hydroxyanilino)-5,7-dimethyl-8-(3-methylbutyl)-7H-pteridin-6-one; C19H23F2N5O2; 2-(3,5-difluoro-4-hydroxyphenylamino)-8-isopentyl-5,7-dimethyl-7,8-dihydropteridin-6(5H)-one; BI-D 1870; CHEMBL573107; GTPL8038; SCHEMBL13881333; CTK8I8998; BDBM25017; DTXSID40648506; BID1870; MolPort-008-266-821; HMS3244D11; HMS3244C12; HMS3244C11; BCPP000343; HMS3651D17; BCP01977; EX-A2471; NSC747342

Indication

Disease Entry	ICD 11	Status	REF
Chronic lymphocytic leukaemia	2A82.0	Preclinical	[1]

• Cross-matching ID:
  PubChem CID: 25023738
  CAS Number: CAS 501437-28-1
  TTD Drug ID: DMK3SAF

Molecule-Related Drug Atlas

Drug(s) Targeting Ribosomal protein S6 kinase alpha-3 (RSK3)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PMID27410995-Compound-Figure3j	DMJRZLB	N. A.	N. A.	Patented	[3]
Indole-based analog 14	DMQURWZ	N. A.	N. A.	Patented	[3]
Pyrrolo[2,3-d]pyrimidine derivative 35	DMXU08A	N. A.	N. A.	Patented	[3]
PMID22765894C8h	DMH5RFU	Discovery agent	N.A.	Investigative	[4]
PMID22564207C25b	DMBMYKQ	Discovery agent	N.A.	Investigative	[5]
BIX 02565	DMNAX1Q	Discovery agent	N.A.	Investigative	[6]

Drug(s) Targeting Ribosomal protein S6 kinase alpha-2 (RSK2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PMID22564207C25b	DMBMYKQ	Discovery agent	N.A.	Investigative	[5]

Drug(s) Targeting Ribosomal protein S6 kinase alpha-1 (RSK1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
1,6-diazanaphthalenes and pyrido[2,3-d] pyrimidine derivative 1	DMUQ9CF	N. A.	N. A.	Patented	[3]
Heterocyclic derivative 26	DM56T1P	N. A.	N. A.	Patented	[3]
1,6-diazanaphthalenes and pyrido[2,3-d] pyrimidine derivative 2	DMPZ0U8	N. A.	N. A.	Patented	[3]
Pyrrolo[2,3-d]pyrimidine derivative 1	DMYUEA6	N. A.	N. A.	Patented	[3]
Pyrrolo[2,3-d]pyrimidine derivative 2	DMJFYK1	N. A.	N. A.	Patented	[3]
PMID19364658C33	DMSE1C3	Discovery agent	N.A.	Investigative	[7]
GSK-1838705A	DM4HLK3	Discovery agent	N.A.	Investigative	[8]

Drug(s) Targeting Ribosomal protein S6 kinase alpha-6 (RSK6)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
US10081632, Compound 25	DM3BDHN	N. A.	N. A.	Patented	[9]
CID 138805970	DMINXMY	N. A.	N. A.	Patented	[9]
PMID22564207C25b	DMBMYKQ	Discovery agent	N.A.	Investigative	[5]

Drug(s) Affected By Poly polymerase 1 (PARP1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[10]
Gefitinib	DM15F0X	Colon adenocarcinoma		Approved	[11]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[12]
Nitric Oxide	DM1RBYG	Hypertension	BA00-BA04	Approved	[13]
Citalopram	DM2G9AE	Acute coronary syndrome	BA41	Approved	[14]
Ciprofloxacin XR	DM2NLS9	Acute gonococcal cervicitis		Approved	[15]
Imipramine	DM2NUH3	Depression	6A70-6A7Z	Approved	[14]
Colchicine	DM2POTE	Acute gout flare	FA25.0	Approved	[16]
Sulindac	DM2QHZU	Acute myelogenous leukaemia	2A41	Approved	[17]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[18]

Drug(s) Affected By Mitogen-activated protein kinase 3 (MAPK3)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[19]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[20]
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[21]
Sertraline	DM0FB1J	Coronary heart disease	BA80.Z	Approved	[22]
Beta-carotene	DM0RXBT	Vitamin deficiency	5B55-5B71	Approved	[23]
Fulvestrant	DM0YZC6	Breast cancer	2C60-2C65	Approved	[24]
Secobarbital	DM14RF5	Epilepsy	8A60-8A68	Approved	[25]
Gefitinib	DM15F0X	Colon adenocarcinoma		Approved	[26]
Fexofenadine	DM17ONX	Allergic rhinitis	CA08.0	Approved	[27]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[28]

Drug(s) Affected By Mitogen-activated protein kinase 1 (MAPK1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Ethanol	DMDRQZU	Chronic pain	MG30	Approved	[29]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[20]
Carvedilol	DMHTEAO	Chronic heart failure	BD1Z	Approved	[30]
Paclitaxel	DMLB81S	Breast carcinoma		Approved	[31]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[32]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[19]
Urokinase	DM0GOUD	Myocardial infarction	BA41-BA43	Approved	[33]
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[34]
Sertraline	DM0FB1J	Coronary heart disease	BA80.Z	Approved	[22]
Beta-carotene	DM0RXBT	Vitamin deficiency	5B55-5B71	Approved	[23]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Ribosomal protein S6 kinase alpha-1 (RSK1)	TTIXKA4	KS6A1_HUMAN	Inhibitor	[1]
Ribosomal protein S6 kinase alpha-2 (RSK2)	TT0ZW9O	KS6A2_HUMAN	Inhibitor	[1]
Ribosomal protein S6 kinase alpha-3 (RSK3)	TTUM2ZR	KS6A3_HUMAN	Inhibitor	[1]
Ribosomal protein S6 kinase alpha-6 (RSK6)	TT3KYWB	KS6A6_HUMAN	Inhibitor	[1]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Post-Translational Modifications	[2]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Post-Translational Modifications	[2]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Protein Interaction/Cellular Processes	[2]

References

• [1] BI-D1870 is a specific inhibitor of the p90 RSK (ribosomal S6 kinase) isoforms in vitro and in vivo. Biochem J. 2007 Jan 1;401(1):29-38.
• [2] Glycogen synthase kinase 3 regulates cell death and survival signaling in tumor cells under redox stress. Neoplasia. 2014 Sep;16(9):710-22.
• [3] Ribosomal S6 kinase (RSK) modulators: a patent review.Expert Opin Ther Pat. 2016 Sep;26(9):1061-78.
• [4] The design, synthesis, and biological evaluation of potent receptor tyrosine kinase inhibitors. Bioorg Med Chem Lett. 2012 Aug 1;22(15):4979-85.
• [5] Discovery of an orally efficacious inhibitor of anaplastic lymphoma kinase. J Med Chem. 2012 May 24;55(10):4580-93.
• [6] Indole RSK inhibitors. Part 2: optimization of cell potency and kinase selectivity. Bioorg Med Chem Lett. 2012 Jan 1;22(1):738-42.
• [7] Identification and SAR of squarate inhibitors of mitogen activated protein kinase-activated protein kinase 2 (MK-2). Bioorg Med Chem. 2009 May 1;17(9):3342-51.
• [8] GSK1838705A inhibits the insulin-like growth factor-1 receptor and anaplastic lymphoma kinase and shows antitumor activity in experimental models of human cancers. Mol Cancer Ther. 2009 Oct;8(10):2811-20.
• [9] Substituted tetrahydropyrido[3,2:4,5]pyrrolo[1,2-a]pyrazine-2-carboxamides as RSK inhibitors. US9771366.
• [10] Cannabidiol enhances cytotoxicity of anti-cancer drugs in human head and neck squamous cell carcinoma. Sci Rep. 2020 Nov 26;10(1):20622. doi: 10.1038/s41598-020-77674-y.
• [11] Evidence of securin-mediated resistance to gefitinib-induced apoptosis in human cancer cells. Chem Biol Interact. 2013 Apr 25;203(2):412-22. doi: 10.1016/j.cbi.2013.03.011. Epub 2013 Mar 22.
• [12] Cigarette smoke and asbestos activate poly-ADP-ribose polymerase in alveolar epithelial cells. J Investig Med. 2001 Jan;49(1):68-76. doi: 10.2310/6650.2001.34092.
• [13] Apoptotic signaling pathways induced by nitric oxide in human lymphoblastoid cells expressing wild-type or mutant p53. Cancer Res. 2004 May 1;64(9):3022-9. doi: 10.1158/0008-5472.can-03-1880.
• [14] The antidepressants imipramine, clomipramine, and citalopram induce apoptosis in human acute myeloid leukemia HL-60 cells via caspase-3 activation. J Biochem Mol Toxicol. 1999;13(6):338-47. doi: 10.1002/(sici)1099-0461(1999)13:6<338::aid-jbt8>3.0.co;2-7.
• [15] Ciprofloxacin mediated cell growth inhibition, S/G2-M cell cycle arrest, and apoptosis in a human transitional cell carcinoma of the bladder cell line. Clin Cancer Res. 2000 Mar;6(3):891-900.
• [16] Investigation of molecular mechanisms underlying the antiproliferative effects of colchicine against PC3 prostate cancer cells. Toxicol In Vitro. 2021 Jun;73:105138. doi: 10.1016/j.tiv.2021.105138. Epub 2021 Mar 6.
• [17] Sulindac enhances adenoviral vector expressing mda-7/IL-24-mediated apoptosis in human lung cancer. Mol Cancer Ther. 2005 Feb;4(2):291-304.
• [18] Methotrexate induces poly(ADP-ribose) polymerase-dependent, caspase 3-independent apoptosis in subsets of proliferating CD4+ T cells. Clin Exp Immunol. 2007 May;148(2):288-95. doi: 10.1111/j.1365-2249.2007.03335.x. Epub 2007 Feb 7.
• [19] Treatment with anticancer agents induces dysregulation of specific Wnt signaling pathways in human ovarian luteinized granulosa cells in vitro. Toxicol Sci. 2013 Nov;136(1):183-92. doi: 10.1093/toxsci/kft175. Epub 2013 Aug 16.
• [20] Progesterone increases csk homologous kinase in HMC-1560 human mast cells and reduces cell proliferation. J Cell Biochem. 2007 Dec 1;102(5):1271-80. doi: 10.1002/jcb.21357.
• [21] Cannabidiol upregulates melanogenesis through CB1 dependent pathway by activating p38 MAPK and p42/44 MAPK. Chem Biol Interact. 2017 Aug 1;273:107-114. doi: 10.1016/j.cbi.2017.06.005. Epub 2017 Jun 7.
• [22] Sertraline, an antidepressant, induces apoptosis in hepatic cells through the mitogen-activated protein kinase pathway. Toxicol Sci. 2014 Feb;137(2):404-15. doi: 10.1093/toxsci/kft254. Epub 2013 Nov 5.
• [23] Growth stimulation of human pulmonary adenocarcinoma cells and small airway epithelial cells by beta-carotene via activation of cAMP, PKA, CREB and ERK1/2. Int J Cancer. 2006 Mar 15;118(6):1370-80. doi: 10.1002/ijc.21537.
• [24] Estrogen and pure antiestrogen fulvestrant (ICI 182 780) augment cell-matrigel adhesion of MCF-7 breast cancer cells through a novel G protein coupled estrogen receptor (GPR30)-to-calpain signaling axis. Toxicol Appl Pharmacol. 2014 Mar 1;275(2):176-81. doi: 10.1016/j.taap.2014.01.005. Epub 2014 Jan 17.
• [25] Inhibition of activator protein 1 by barbiturates is mediated by differential effects on mitogen-activated protein kinases and the small G proteins ras and rac-1. J Pharmacol Exp Ther. 2004 Dec;311(3):1232-40. doi: 10.1124/jpet.104.071332. Epub 2004 Jul 19.
• [26] Growth of hormone-dependent MCF-7 breast cancer cells is promoted by constitutive caveolin-1 whose expression is lost in an EGF-R-mediated manner during development of tamoxifen resistance. Breast Cancer Res Treat. 2010 Feb;119(3):575-91. doi: 10.1007/s10549-009-0355-8. Epub 2009 Mar 15.
• [27] Effect of histamine H1 receptor antagonists on TARC/CCL17 and MDC/CCL22 production from CD14+ cells induced by antigenic stimulation in vitro. Int Arch Allergy Immunol. 2011;155(1):38-51. doi: 10.1159/000318720. Epub 2010 Nov 25.
• [28] SIRT3 Mediates the Antioxidant Effect of Hydrogen Sulfide in Endothelial Cells. Antioxid Redox Signal. 2016 Feb 20;24(6):329-43. doi: 10.1089/ars.2015.6331. Epub 2015 Nov 10.
• [29] Downregulation of mitogen-activated protein kinases (MAPKs) in chronic ethanol-induced fatty liver. Toxicol Mech Methods. 2020 Jul;30(6):407-416. doi: 10.1080/15376516.2020.1747126. Epub 2020 Apr 1.
• [30] A unique mechanism of beta-blocker action: carvedilol stimulates beta-arrestin signaling. Proc Natl Acad Sci U S A. 2007 Oct 16;104(42):16657-62. doi: 10.1073/pnas.0707936104. Epub 2007 Oct 9.
• [31] The stent-eluting drugs sirolimus and paclitaxel suppress healing of the endothelium by induction of autophagy. Am J Pathol. 2009 Nov;175(5):2226-34.
• [32] Modulation of apoptosis in HaCaT keratinocytes via differential regulation of ERK signaling pathway by flavonoids. J Biol Chem. 2005 Sep 9;280(36):31498-507. doi: 10.1074/jbc.M505537200. Epub 2005 Jul 13.
• [33] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
• [34] Cannabidiol Modulates the Immunophenotype and Inhibits the Activation of the Inflammasome in Human Gingival Mesenchymal Stem Cells. Front Physiol. 2016 Nov 24;7:559. doi: 10.3389/fphys.2016.00559. eCollection 2016.