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

General Information of Drug (ID: DM58KHY)

• Drug Name: dihydrosphingosine-1-phosphate Drug Info
• Synonyms: sphinganine-phosphate; dihydroS1P
• Cross-matching ID:
  PubChem CID: 644260
  ChEBI ID: CHEBI:16893
  CAS Number: CAS 19794-97-9
  TTD Drug ID: DM58KHY

Molecule-Related Drug Atlas

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	[5]
AFD(R)	DME9Y8Q	Discovery agent	N.A.	Investigative	[6]
FTY720-phosphate	DMDZBQH	Discovery agent	N.A.	Investigative	[7]
VPC03090-P	DMIXUM3	Discovery agent	N.A.	Investigative	[8]
KRP 203-phosphate	DMLIK7X	Discovery agent	N.A.	Investigative	[9]
phytosphingosine 1-phosphate	DMWJCST	Discovery agent	N.A.	Investigative	[2]

Drug(s) Targeting G-protein coupled receptor 63 (GPR63)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
dioleoylphosphatidic acid	DM7D6JV	Discovery agent	N.A.	Investigative	[1]

Drug(s) Affected By Prostaglandin G/H synthase 2 (PTGS2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Eicosapentaenoic acid/docosa-hexaenoic acid	DMMUCG4	Hypertriglyceridemia	5C80.1	Approved	[10]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[11]
Gamolenic acid	DMQN30Z	Allergy	4A80-4A85	Approved	[12]
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[13]
Flupentixol	DM0DJ9O	Schizophrenia	6A20	Approved	[14]
Sertraline	DM0FB1J	Coronary heart disease	BA80.Z	Approved	[15]
Ibandronate	DM0QZBN	Hypercalcaemia	5B91.0	Approved	[16]
Fulvestrant	DM0YZC6	Breast cancer	2C60-2C65	Approved	[17]
Fexofenadine	DM17ONX	Allergic rhinitis	CA08.0	Approved	[18]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[19]

Drug(s) Affected By Sphingosine-1-phosphate transporter SPNS2 (SPNS2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[20]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[21]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[22]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[23]
Fenofibrate	DMFKXDY	Coronary atherosclerosis		Approved	[24]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[25]
Sphingosine-1-phosphate	DMJCQKA	Acne vulgaris	ED80	Phase 1	[4]
(+)-JQ1	DM1CZSJ	Testicular cancer	2C80	Phase 1	[26]
Benzo(a)pyrene	DMN7J43	N. A.	N. A.	Phase 1	[27]
PMID28460551-Compound-2	DM4DOUB	N. A.	N. A.	Patented	[28]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
G-protein coupled receptor 63 (GPR63)	TT2D5VM	GPR63_HUMAN	Agonist	[1]
Sphingosine-1-phosphate receptor 4 (S1PR4)	TTZ8C5Q	S1PR4_HUMAN	Agonist	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Prostaglandin G/H synthase 2 (PTGS2)	OT75U9M4	PGH2_HUMAN	Gene/Protein Processing	[3]
Sphingosine-1-phosphate transporter SPNS2 (SPNS2)	OTPODAPU	SPNS2_HUMAN	Regulation of Drug Effects	[4]

References

• [1] Sphingosine 1-phosphate and dioleoylphosphatidic acid are low affinity agonists for the orphan receptor GPR63. Cell Signal. 2003 Apr;15(4):435-46.
• [2] 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.
• [3] Prostacyclin induction by high-density lipoprotein (HDL) in vascular smooth muscle cells depends on sphingosine 1-phosphate receptors: effect of simvastatin. Thromb Haemost. 2008 Jul;100(1):119-26.
• [4] Downregulation of the S1P Transporter Spinster Homology Protein 2 (Spns2) Exerts an Anti-Fibrotic and Anti-Inflammatory Effect in Human Renal Proximal Tubular Epithelial Cells. Int J Mol Sci. 2018 May 17;19(5):1498. doi: 10.3390/ijms19051498.
• [5] 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.
• [6] 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.
• [7] The immune modulator FTY720 targets sphingosine 1-phosphate receptors. J Biol Chem. 2002 Jun 14;277(24):21453-7.
• [8] Characterization of a sphingosine 1-phosphate receptor antagonist prodrug. J Pharmacol Exp Ther. 2011 Sep;338(3):879-89.
• [9] 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.
• [10] Docosahexaenoic acid regulates gene expression in HUVEC cells treated with polycyclic aromatic hydrocarbons. Toxicol Lett. 2015 Jul 16;236(2):75-81.
• [11] Etoposide induces necrosis through p53-mediated antiapoptosis in human kidney proximal tubule cells. Toxicol Sci. 2015 Nov;148(1):204-19.
• [12] Conjugated linoleic acid, unlike other unsaturated fatty acids, strongly induces glutathione synthesis without any lipoperoxidation. Br J Nutr. 2006 Nov;96(5):811-9.
• [13] COX-2 and PPAR-gama confer cannabidiol-induced apoptosis of human lung cancer cells. Mol Cancer Ther. 2013 Jan;12(1):69-82.
• [14] Mitochondrial involvement in schizophrenia and other functional psychoses. Neurochem Res. 1996 Sep;21(9):995-1004.
• [15] Immunomodulatory effect of selective serotonin reuptake inhibitors (SSRIs) on human T lymphocyte function and gene expression. Eur Neuropsychopharmacol. 2007 Dec;17(12):774-80.
• [16] Stimulation of cyclooxygenase-2 expression by bone-derived transforming growth factor-beta enhances bone metastases in breast cancer. Cancer Res. 2006 Feb 15;66(4):2067-73.
• [17] Arsenite and cadmium promote the development of mammary tumors. Carcinogenesis. 2020 Jul 14;41(7):1005-1014. doi: 10.1093/carcin/bgz176.
• [18] An in vitro coculture system of human peripheral blood mononuclear cells with hepatocellular carcinoma-derived cells for predicting drug-induced liver injury. Arch Toxicol. 2021 Jan;95(1):149-168. doi: 10.1007/s00204-020-02882-4. Epub 2020 Aug 20.
• [19] A2E selectively induces cox-2 in ARPE-19 and human neural cells. Curr Eye Res. 2006 Mar;31(3):259-63.
• [20] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [21] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [22] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [23] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [24] Transcriptomic analysis of untreated and drug-treated differentiated HepaRG cells over a 2-week period. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):27-35.
• [25] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [26] Loss of TRIM33 causes resistance to BET bromodomain inhibitors through MYC- and TGF-beta-dependent mechanisms. Proc Natl Acad Sci U S A. 2016 Aug 2;113(31):E4558-66.
• [27] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [28] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.