Details of the Drug

General Information of Drug (ID: DMBGUDR)

• Drug Name: Safingol
• Synonyms: Kynac; Kynacyte; SPC-100270; Safingol < Rec INN; L-threo-Dihydrosphingosine; SPC-100271 (HCl); (2S,3S)-2-Aminooctadecane-1,3-diol

Indication

Disease Entry	ICD 11	Status	REF
Psoriasis vulgaris	EA90	Phase 1	[1], [2]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 2:
  Molecular Weight (mw); 301.5
  Topological Polar Surface Area (xlogp); 5.8
  Rotatable Bond Count (rotbonds); 16
  Hydrogen Bond Donor Count (hbonddonor); 3
  Hydrogen Bond Acceptor Count (hbondacc); 3
• Chemical Identifiers:
  Formula: C18H39NO2
  IUPAC Name: (2S,3S)-2-aminooctadecane-1,3-diol
  Canonical SMILES: CCCCCCCCCCCCCCC[C@@H]([C@H](CO)N)O
  InChI: InChI=1S/C18H39NO2/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-18(21)17(19)16-20/h17-18,20-21H,2-16,19H2,1H3/t17-,18-/m0/s1
  InChIKey: OTKJDMGTUTTYMP-ROUUACIJSA-N
• Cross-matching ID:
  PubChem CID: 3058739
  CAS Number: 15639-50-6
  DrugBank ID: DB11924
  TTD ID: D07CAQ
  INTEDE ID: DR1808

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Protein kinase C (PRKC)	TTYVX59	NOUNIPROTAC	Inhibitor	[3]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4) Main DME	DE4LYSA	CP3A4_HUMAN	Substrate	[4]

References

• [1] ClinicalTrials.gov (NCT00084812) Safingol and Cisplatin in Treating Patients With Locally Advanced or Metastatic Solid Tumors. U.S. National Institutes of Health.
• [2] A phase I clinical trial of safingol in combination with cisplatin in advanced solid tumors. Clin Cancer Res. 2011 Apr 15;17(8):2484-92.
• [3] The role of protein kinase C in the synergistic interaction of safingol and irinotecan in colon cancer cells. Int J Oncol. 2009 Dec;35(6):1463-71.
• [4] Sex differences in rat hepatic cytolethality of the protein kinase C inhibitor safingol: role of biotransformation. Toxicol Appl Pharmacol. 1996 Apr;137(2):173-81.
• [5] Expression levels and activation of a PXR variant are directly related to drug resistance in osteosarcoma cell lines. Cancer. 2007 Mar 1;109(5):957-65.
• [6] Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
• [7] Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. J Pharmacol Exp Ther. 2004 Sep;310(3):1062-75.
• [8] Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
• [9] Metabolic interactions between acetaminophen (paracetamol) and two flavonoids, luteolin and quercetin, through in-vitro inhibition studies. J Pharm Pharmacol. 2017 Dec;69(12):1762-1772.
• [10] Potent mechanism-based inhibition of CYP3A4 by imatinib explains its liability to interact with CYP3A4 substrates. Br J Pharmacol. 2012 Apr;165(8):2787-98.
• [11] Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
• [12] The metabolism of zidovudine by human liver microsomes in vitro: formation of 3'-amino-3'-deoxythymidine. Biochem Pharmacol. 1994 Jul 19;48(2):267-76.
• [13] Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
• [14] Characterization of the interaction of hypericin with protein kinase C in U-87 MG human glioma cells. Photochem Photobiol. 2006 May-Jun;82(3):720-8.
• [15] Targeting the protein kinase C family: are we there yet. Nat Rev Cancer. 2007 Jul;7(7):554-62.
• [16] Effect of anti-tumor agents cisplatin and cycloplatam on membrane protein kinase C activity in murine T-lymphocytes. Biokhimiia. 1996 Oct;61(10):1866-73.
• [17] What's next in the pipeline. Am J Transplant. 2008 Oct;8(10):1972-81.
• [18] WO patent application no. 2014,0853,81, Pharmaceutical combinations.
• [19] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [20] Inhibitory effect of glutamate release from rat cerebrocortical synaptosomes by dextromethorphan and its metabolite 3-hydroxymorphinan. Neurochem Int. 2009 Jul;54(8):526-34.
• [21] Changes in Serum Cytokine Profile after AEB071 (Sotrastaurin) or Tacrolimus versus Their Combinations in Rat Heterotopic Cardiac Allografts. J Korean Soc Transplant. 2012 Dec;26(4):248-253.
• [22] Protein kinase C as a molecular target for cancer prevention by selenocompounds. Nutr Cancer. 2001;40(1):55-63.
• [23] Drugs used to treat Parkinson's disease, present status and future directions. CNS Neurol Disord Drug Targets. 2008 Oct;7(4):321-42.