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

General Information of Drug (ID: DMBGUDR)

• Drug Name: SAFINGOL Drug Info
• 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]

• Cross-matching ID:
  PubChem CID: 3058739
  CAS Number: CAS 15639-50-6
  TTD Drug ID: DMBGUDR
  INTEDE Drug ID: DR1808

Molecule-Related Drug Atlas

Drug(s) Targeting Protein kinase C (PRKC)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Synthetic hypericin	DMXU4ON	Virus infection	1A24-1D9Z	Phase 3	[4]
APH-0812	DM756GE	Human immunodeficiency virus-1 infection	1C62	Phase 2	[5]
CYCLOPLATAM	DMXR8WN	Solid tumour/cancer	2A00-2F9Z	Phase 2	[6]
AEB07	DMJVN89	Transplant rejection	NE84	Phase 2	[7]
HO/03/03	DMA6HQJ	Diabetic foot ulcer	BD54	Phase 2	[8]
Bryostatin-1	DM1JOXY	Alzheimer disease	8A20	Phase 2	[9]
LXS196	DM65MEL	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[10]
GCC-1290K	DMJ7WRI	Parkinson disease	8A00.0	Phase 1	[11]
AEB701	DM8I4G0	Melanoma	2C30	Phase 1	[12]
Tecadenoson	DM9T6MS	Atrial fibrillation	BC81.3	Discontinued in Phase 3	[13]

Drug(s) Metabolized By Cytochrome P450 3A4 (CYP3A4)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[14]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[15]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[16]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[17]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[18]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[19]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[20]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[21]
Prasterone	DM67VKL	Chronic obstructive pulmonary disease	CA22	Approved	[15]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[22]

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	[2]

Drug-Metabolizing Enzyme (DME)

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

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] 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.
• [3] 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.
• [4] 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.
• [5] Targeting the protein kinase C family: are we there yet. Nat Rev Cancer. 2007 Jul;7(7):554-62.
• [6] 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.
• [7] What's next in the pipeline. Am J Transplant. 2008 Oct;8(10):1972-81.
• [8] WO patent application no. 2014,0853,81, Pharmaceutical combinations.
• [9] Bryostatin-1: a promising compound for neurological disorders. Front Pharmacol. 2023 Jun 7;14:1187411.
• [10] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [11] Inhibitory effect of glutamate release from rat cerebrocortical synaptosomes by dextromethorphan and its metabolite 3-hydroxymorphinan. Neurochem Int. 2009 Jul;54(8):526-34.
• [12] 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.
• [13] Protein kinase C as a molecular target for cancer prevention by selenocompounds. Nutr Cancer. 2001;40(1):55-63.
• [14] 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.
• [15] Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
• [16] 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.
• [17] Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
• [18] 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.
• [19] 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.
• [20] Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
• [21] 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.
• [22] 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.