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

General Information of Drug (ID: DMWVH62)

• Drug Name: SCH772984 Drug Info
• Synonyms: SCH-772984

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1]

• Cross-matching ID:
  PubChem CID: 24866313
  TTD Drug ID: DMWVH62

Molecule-Related Drug Atlas

Drug(s) Targeting Extracellular signal-regulated kinase 2 (ERK2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
BVD-523	DMNB4XK	Melanoma	2C30	Phase 2	[3]
HH2710	DM0C5MV	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[4]
ASTX029	DMVZXIA	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[5]
VAN-10-4-eluting stent	DM3ZW6A	Artery stenosis	BD52	Phase 1	[6]
GDC-0994	DMFC2OY	Solid tumour/cancer	2A00-2F9Z	Phase 1	[7]
JSI-1187	DMVJWBS	Solid tumour/cancer	2A00-2F9Z	Phase 1	[8]
LY3214996	DMFDAY7	Solid tumour/cancer	2A00-2F9Z	Phase 1	[9]
CHIR-99021	DMB8MNU	Allergic inflammation	4A80-4A85	Patented	[10]
COR-D	DMLXMCB	T-cell leukaemia	2A90	Preclinical	[11]
SB220025	DMSBUET	Arthritis	FA20	Terminated	[12]

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	[13]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[14]
Carvedilol	DMHTEAO	Chronic heart failure	BD1Z	Approved	[15]
Paclitaxel	DMLB81S	Breast carcinoma		Approved	[16]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[17]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[18]
Urokinase	DM0GOUD	Myocardial infarction	BA41-BA43	Approved	[19]
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[20]
Sertraline	DM0FB1J	Coronary heart disease	BA80.Z	Approved	[21]
Beta-carotene	DM0RXBT	Vitamin deficiency	5B55-5B71	Approved	[22]

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	[18]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[14]
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[23]
Sertraline	DM0FB1J	Coronary heart disease	BA80.Z	Approved	[21]
Beta-carotene	DM0RXBT	Vitamin deficiency	5B55-5B71	Approved	[22]
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]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Extracellular signal-regulated kinase 2 (ERK2)	TT4TQBX	MK01_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]

References

• [1] Discovery of a novel ERK inhibitor with activity in models of acquired resistance to BRAF and MEK inhibitors. Cancer Discov. 2013 Jul;3(7):742-50.
• [2] 3,4,5-Tri-O-caffeoylquinic acid methyl ester isolated from Lonicera japonica Thunb. Flower buds facilitates hepatitis B virus replication in HepG2.2.15 cells. Food Chem Toxicol. 2020 Apr;138:111250. doi: 10.1016/j.fct.2020.111250. Epub 2020 Mar 7.
• [3] DOI: 10.1158/1538-7445.AM2015-4693
• [4] Clinical pipeline report, company report or official report of HaiHe Biopharma.
• [5] Clinical pipeline report, company report or official report of Astex Pharmaceuticals.
• [6] WO patent application no. 2013,1850,32, Nanotherapeutics for drug targeting.
• [7] ERK Mutations Confer Resistance to Mitogen-Activated Protein Kinase Pathway Inhibitors
• [8] National Cancer Institute Drug Dictionary (drug name JSI1187).
• [9] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [10] Selective glycogen synthase kinase 3 inhibitors potentiate insulin activation of glucose transport and utilization in vitro and in vivo. Diabetes. 2003 Mar;52(3):588-95.
• [11] Corchorusin-D directed apoptosis of K562 cells occurs through activation of mitochondrial and death receptor pathways and suppression of AKT/PKB pathway. Cell Physiol Biochem. 2012;30(4):915-26.
• [12] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [13] 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.
• [14] 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.
• [15] 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.
• [16] 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.
• [17] 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.
• [18] 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.
• [19] 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.
• [20] 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.
• [21] 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.
• [22] 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.
• [23] 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.
• [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.