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

General Information of Drug (ID: DMDZBQH)

• Drug Name: FTY720-phosphate Drug Info
• Synonyms: fingolimod phosphate

Indication

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

• Cross-matching ID:
  PubChem CID: 9908268
  ChEBI ID: CHEMBL114606
  CAS Number: CAS 402616-23-3
  TTD Drug ID: DMDZBQH

Molecule-Related Drug Atlas

Drug(s) Targeting Sphingosine-1-phosphate receptor 3 (S1PR3)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
US9522888, 575	DM6UXZK	N. A.	N. A.	Patented	[5]
US9617250, Example 1 Example 204 of D1	DM89LKQ	N. A.	N. A.	Patented	[6]
YYDJCLCSBYCSCO-UHFFFAOYSA-N	DMA91FM	N. A.	N. A.	Patented	[7]
US9216972, 61	DM7AHQE	N. A.	N. A.	Patented	[8]
US9670220, 77	DMZG1HO	N. A.	N. A.	Patented	[9]
US10179791, Compound 296	DMLZBRM	N. A.	N. A.	Patented	[10]
JCXGHZCWAHCYGY-UHFFFAOYSA-N	DMER7QX	N. A.	N. A.	Patented	[7]
US9216972, 67	DMXR5SZ	N. A.	N. A.	Patented	[8]
US10166249, Example 695	DMVMNP1	N. A.	N. A.	Patented	[11]
US9181182, 40	DM3QIF4	N. A.	N. A.	Patented	[12]

Drug(s) Targeting Sphingosine-1-phosphate receptor 1 (S1PR1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Siponimod	DM2R86O	Multiple sclerosis	8A40	Approved	[13]
Fingolimod	DM5JVAN	Multiple sclerosis	8A40	Approved	[14]
Ozanimod	DMT6AM2	Multiple sclerosis	8A40	Approved	[15]
Etrasimod	DMT0A3Y	Ulcerative colitis	DD71	Approved	[16]
Ponesimod	DMEAOYJ	Multiple sclerosis	8A40	Approved	[17]
MT-1303	DMSE9TH	Crohn disease	DD70	Phase 2	[18]
ONO-4641	DMLUM3Y	Rheumatoid arthritis	FA20	Phase 2	[19]
KRP-203	DMOW9X2	Cutaneous lupus erythematosus	EB5Z	Phase 2	[19]
VTX-002	DMZ8Z5A	Ulcerative colitis	DD71	Phase 2	[20]
CBP-307	DM3TH6Y	Ulcerative colitis	DD71	Phase 2	[21]

Drug(s) Targeting Sphingosine-1-phosphate receptor 4 (S1PR4)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
AUY954	DMVGIO5	Discovery agent	N.A.	Investigative	[22]
AFD(R)	DME9Y8Q	Discovery agent	N.A.	Investigative	[23]
VPC03090-P	DMIXUM3	Discovery agent	N.A.	Investigative	[24]
dihydrosphingosine-1-phosphate	DM58KHY	N. A.	N. A.	Investigative	[25]
KRP 203-phosphate	DMLIK7X	Discovery agent	N.A.	Investigative	[26]
phytosphingosine 1-phosphate	DMWJCST	Discovery agent	N.A.	Investigative	[25]

Drug(s) Targeting Sphingosine-1-phosphate receptor 5 (S1PR5)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ASP-4058	DM1RD0T	Multiple sclerosis	8A40	Phase 1	[27]
AUY954	DMVGIO5	Discovery agent	N.A.	Investigative	[22]
AFD(R)	DME9Y8Q	Discovery agent	N.A.	Investigative	[23]
VPC03090-P	DMIXUM3	Discovery agent	N.A.	Investigative	[24]
VPC44116	DMQ4OTJ	Discovery agent	N.A.	Investigative	[28]

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	[29]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[30]
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[31]
Sertraline	DM0FB1J	Coronary heart disease	BA80.Z	Approved	[32]
Beta-carotene	DM0RXBT	Vitamin deficiency	5B55-5B71	Approved	[33]
Fulvestrant	DM0YZC6	Breast cancer	2C60-2C65	Approved	[34]
Secobarbital	DM14RF5	Epilepsy	8A60-8A68	Approved	[35]
Gefitinib	DM15F0X	Colon adenocarcinoma		Approved	[36]
Fexofenadine	DM17ONX	Allergic rhinitis	CA08.0	Approved	[37]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[38]

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	[39]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[30]
Carvedilol	DMHTEAO	Chronic heart failure	BD1Z	Approved	[40]
Paclitaxel	DMLB81S	Breast carcinoma		Approved	[41]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[42]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[29]
Urokinase	DM0GOUD	Myocardial infarction	BA41-BA43	Approved	[43]
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[44]
Sertraline	DM0FB1J	Coronary heart disease	BA80.Z	Approved	[32]
Beta-carotene	DM0RXBT	Vitamin deficiency	5B55-5B71	Approved	[33]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Sphingosine-1-phosphate receptor 1 (S1PR1)	TT9JZCK	S1PR1_HUMAN	Agonist	[2]
Sphingosine-1-phosphate receptor 3 (S1PR3)	TTDYP7I	S1PR3_HUMAN	Agonist	[3]
Sphingosine-1-phosphate receptor 4 (S1PR4)	TTZ8C5Q	S1PR4_HUMAN	Agonist	[2]
Sphingosine-1-phosphate receptor 5 (S1PR5)	TTDZCKV	S1PR5_HUMAN	Agonist	[3]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Mitogen-activated protein kinase 1 (MAPK1)	OTH85PI5	MK01_HUMAN	Post-Translational Modifications	[4]
Mitogen-activated protein kinase 3 (MAPK3)	OTCYKGKO	MK03_HUMAN	Post-Translational Modifications	[4]

References

• [1] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 2924).
• [2] The immune modulator FTY720 targets sphingosine 1-phosphate receptors. J Biol Chem. 2002 Jun 14;277(24):21453-7.
• [3] Immune cell regulation and cardiovascular effects of sphingosine 1-phosphate receptor agonists in rodents are mediated via distinct receptor subtypes. J Pharmacol Exp Ther. 2004 May;309(2):758-68.
• [4] Adverse effect of FTY720P on colonic Na(+) /K(+) ATPase is mediated via ERK, p38MAPK, PKC, and PI3K. J Appl Toxicol. 2023 Feb;43(2):220-229. doi: 10.1002/jat.4375. Epub 2022 Aug 17.
• [5] Substituted bicyclic compounds. US9522888.
• [6] Pyridin-4-yl derivatives. US9617250.
• [7] 6-amino-pyrimidine-4-carboxamide derivatives and related compounds which bind to the sphingosine 1-phosphate (S1P) receptor for the treatment of multiple sclerosis. US9150519.
• [8] Tricyclic heterocyclic compounds. US9216972.
• [9] Fused heterocyclic derivatives as S1P modulators. US9670220.
• [10] Spiro-cyclic amine derivatives as S1P modulators. US10179791.
• [11] Substituted bicyclic compounds. US10166249.
• [12] S1P receptors modulators. US9181182.
• [13] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
• [14] Mullard A: 2010 FDA drug approvals. Nat Rev Drug Discov. 2011 Feb;10(2):82-5.
• [15] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
• [16] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [17] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2021
• [18] Sphingosine 1-Phosphate Receptor Modulators in Multiple Sclerosis. CNS Drugs. 2015 Jul;29(7):565-75.
• [19] Targeting the sphingosine-1-phosphate axis in cancer, inflammation and beyond. Nat Rev Drug Discov. 2013 Sep;12(9):688-702.
• [20] Clinical pipeline report, company report or official report of Ventyx Biosciences
• [21] Clinical pipeline report, company report or official report of Connect Biopharma
• [22] A monoselective sphingosine-1-phosphate receptor-1 agonist prevents allograft rejection in a stringent rat heart transplantation model. Chem Biol. 2006 Nov;13(11):1227-34.
• [23] Sphingosine 1-phosphate (S1P) receptor subtypes S1P1 and S1P3, respectively, regulate lymphocyte recirculation and heart rate. J Biol Chem. 2004 Apr 2;279(14):13839-48.
• [24] Characterization of a sphingosine 1-phosphate receptor antagonist prodrug. J Pharmacol Exp Ther. 2011 Sep;338(3):879-89.
• [25] Phytosphingosine 1-phosphate: a high affinity ligand for the S1P(4)/Edg-6 receptor. Biochem Biophys Res Commun. 2002 Sep 27;297(3):600-6.
• [26] A novel sphingosine 1-phosphate receptor agonist, 2-amino-2-propanediol hydrochloride (KRP-203), regulates chronic colitis in interleukin-10 gene-d... J Pharmacol Exp Ther. 2008 Jan;324(1):276-83.
• [27] ASP4058, a novel agonist for sphingosine 1-phosphate receptors 1 and 5, ameliorates rodent experimental autoimmune encephalomyelitis with a favorable safety profile. PLoS One. 2014 Oct 27;9(10):e110819.
• [28] Synthesis and biological evaluation of gamma-aminophosphonates as potent, subtype-selective sphingosine 1-phosphate receptor agonists and antagonists. Bioorg Med Chem. 2007 Jan 15;15(2):663-77.
• [29] 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.
• [30] 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.
• [31] 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.
• [32] 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.
• [33] 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.
• [34] 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.
• [35] 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.
• [36] 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.
• [37] 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.
• [38] 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.
• [39] 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.
• [40] 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.
• [41] 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.
• [42] 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.
• [43] 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.
• [44] 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.