Details of the Drug

General Information of Drug (ID: DMRD5SP)

• Drug Name: Fenretinide
• Synonyms: RT-101; ST-602; SYT-101; Fenretinide (pulmonary Pseudomonas aeruginosa infections in cystic fibrosis), McGill University; LXS/4-HPR; Fenretinide (Ewing's sarcoma), Cancer Research UK; Fenretinide (ILE formulation), Children's Hospital LA; Fenretinide (intralipid emulsion formulation), Children's Hospital of Los Angeles; Fenretinide (intravenous, cancer), SciTech Development; Fenretinide (iv), Children's Hospital LA; Fenretinide (oral, AMD), Sytera; Fenretinide (soft gel capsule, AMD), ReVision Therapeutics; Fenretinide (soft gel capsule, AMD), Sirion; Fenretinide (topical, actinic keratosis and cancer), SciTech Development; N-(4-hydroxyphenyl)retinamide; Fenretinide (intravenous emulsion, lymphoma/solid tumors/pediatric neuroblastomas/pediatric leukemia), CerRx; Fenretinide (oral powder/Lym-X-Sorb, neuroblastoma), BioMolecular Products; 4-HPR

Indication

Disease Entry	ICD 11	Status	REF
Macular degeneration	9B78.3	Phase 3	[1]
Lymphoma	2A80-2A86	Phase 2	[2]
Peripheral T-cell lymphoma	2A90.C	Phase 2	[3]
Solid tumour/cancer	2A00-2F9Z	Phase 2	[2]
Tumour	2A00-2F9Z	Phase 1	[2]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 1:
  Molecular Weight (mw); 391.5
  Topological Polar Surface Area (xlogp); 7.3
  Rotatable Bond Count (rotbonds); 6
  Hydrogen Bond Donor Count (hbonddonor); 2
  Hydrogen Bond Acceptor Count (hbondacc); 2
• Chemical Identifiers:
  Formula: C26H33NO2
  IUPAC Name: (2E,4E,6E,8E)-N-(4-hydroxyphenyl)-3,7-dimethyl-9-(2,6,6-trimethylcyclohexen-1-yl)nona-2,4,6,8-tetraenamide
  Canonical SMILES: CC1=C(C(CCC1)(C)C)/C=C/C(=C/C=C/C(=C/C(=O)NC2=CC=C(C=C2)O)/C)/C
  InChI: InChI=1S/C26H33NO2/c1-19(11-16-24-21(3)10-7-17-26(24,4)5)8-6-9-20(2)18-25(29)27-22-12-14-23(28)15-13-22/h6,8-9,11-16,18,28H,7,10,17H2,1-5H3,(H,27,29)/b9-6+,16-11+,19-8+,20-18+
  InChIKey: AKJHMTWEGVYYSE-FXILSDISSA-N
• Cross-matching ID:
  PubChem CID: 5288209
  ChEBI ID: CHEBI:42588
  CAS Number: 65646-68-6
  DrugBank ID: DB05076
  TTD ID: D08JAC
  INTEDE ID: DR1893

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Retinoic acid receptor (RAR)	TTOD7B3	NOUNIPROTAC	Modulator	[4]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 2C8 (CYP2C8) Main DME	DES5XRU	CP2C8_HUMAN	Substrate	[5]

References

• [1] ClinicalTrials.gov (NCT00003075) Fenretinide in Treating Patients With Cervical Neoplasia. U.S. National Institutes of Health.
• [2] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [3] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [4] National Cancer Institute Drug Dictionary (drug id 39582).
• [5] Characterization of the metabolism of fenretinide by human liver microsomes, cytochrome P450 enzymes and UDP-glucuronosyltransferases. Br J Pharmacol. 2011 Feb;162(4):989-99.
• [6] Roles of cytochromes P450 1A2, 2A6, and 2C8 in 5-fluorouracil formation from tegafur, an anticancer prodrug, in human liver microsomes. Drug Metab Dispos. 2000 Dec;28(12):1457-63.
• [7] Role of cytochrome P450 2C8 in drug metabolism and interactions. Pharmacol Rev. 2016 Jan;68(1):168-241.
• [8] Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
• [9] Differential expression and function of CYP2C isoforms in human intestine and liver. Pharmacogenetics. 2003 Sep;13(9):565-75.
• [10] Analysis of human cytochrome P450 2C8 substrate specificity using a substrate pharmacophore and site-directed mutants. Biochemistry. 2004 Dec 14;43(49):15379-92.
• [11] Interaction of sorafenib and cytochrome P450 isoenzymes in patients with advanced melanoma: a phase I/II pharmacokinetic interaction study. Cancer Chemother Pharmacol. 2011 Nov;68(5):1111-8.
• [12] PharmGKB summary: mycophenolic acid pathway. Pharmacogenet Genomics. 2014 Jan;24(1):73-9.
• [13] Possible involvement of multiple human cytochrome P450 isoforms in the liver metabolism of propofol. Br J Anaesth. 1998 Jun;80(6):788-95.
• [14] Vitamins and cofactors: highlights of ESBOC 2009. Nat Chem Biol. 2009 Aug;5(8):530-3.
• [15] Retinoids--which dermatological indications will benefit in the near future Skin Pharmacol Appl Skin Physiol. 2001 Sep-Oct;14(5):303-15.
• [16] Retinoid agonist isotretinoin ameliorates obstructive renal injury. J Urol. 2003 Oct;170(4 Pt 1):1398-402.
• [17] A review of adapalene in the treatment of acne vulgaris. J Adolesc Health. 2008 Nov;43(5):421-4.
• [18] Peretinoin, an acyclic retinoid, improves the hepatic gene signature of chronic hepatitis C following curative therapy of hepatocellular carcinoma. BMC Cancer. 2013 Apr 15;13:191.
• [19] 13-cis retinoic acid exerts its specific activity on human sebocytes through selective intracellular isomerization to all-trans retinoic acid and binding to retinoid acid receptors. J Invest Dermatol. 2000 Aug;115(2):321-7.
• [20] Chromosomal translocation t(15;17) in human acute promyelocytic leukemia fuses RAR alpha with a novel putative transcription factor, PML. Cell. 1991 Aug 23;66(4):663-74.
• [21] Initial clinical trial of oral TAC-101, a novel retinoic acid receptor-alpha selective retinoid, in patients with advanced cancer. J Clin Oncol. 2002 Aug 15;20(16):3522-32.
• [22] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800027956)
• [23] An antagonist of retinoic acid receptors more effectively inhibits growth of human prostate cancer cells than normal prostate epithelium. Br J Cancer. 2004 Aug 2;91(3):580-8.