Details of the Drug

General Information of Drug (ID: DML1DGP)

• Drug Name: FOROPAFANT
• Synonyms: SR-27417; Foropafant; 2-[N-[2-(Dimethylamino)ethyl]-N-(3-pyridylmethyl)amino]-4-(2,4,6-triisopropylphenyl)thiazole

Indication

Disease Entry	ICD 11	Status	REF
Asthma	CA23	Discontinued in Phase 3	[1], [2]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 1:
  Molecular Weight (mw); 464.7
  Topological Polar Surface Area (xlogp); 6.9
  Rotatable Bond Count (rotbonds); 10
  Hydrogen Bond Donor Count (hbonddonor); 0
  Hydrogen Bond Acceptor Count (hbondacc); 5
• Chemical Identifiers:
  Formula: C28H40N4S
  IUPAC Name: N,N-dimethyl-N'-(pyridin-3-ylmethyl)-N'-[4-[2,4,6-tri(propan-2-yl)phenyl]-1,3-thiazol-2-yl]ethane-1,2-diamine
  Canonical SMILES: CC(C)C1=CC(=C(C(=C1)C(C)C)C2=CSC(=N2)N(CCN(C)C)CC3=CN=CC=C3)C(C)C
  InChI: InChI=1S/C28H40N4S/c1-19(2)23-14-24(20(3)4)27(25(15-23)21(5)6)26-18-33-28(30-26)32(13-12-31(7)8)17-22-10-9-11-29-16-22/h9-11,14-16,18-21H,12-13,17H2,1-8H3
  InChIKey: VVBFISAUNSXQGZ-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 119368
  CAS Number: 136468-36-5
  TTD ID: D05YUK

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Platelet-activating factor receptor (PTAFR)	TTQL5VC	PTAFR_HUMAN	Antagonist	[3], [4], [5]

Molecular Expression Atlas of This Drug

• The Studied Disease: Asthma
• ICD Disease Classification: CA23

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Platelet-activating factor receptor (PTAFR)	DTT	PTAFR	3.53E-02	0.33	2.12

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: 1856).
• [2] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002078)
• [3] Biochemical and pharmacological activities of SR 27417, a highly potent, long-acting platelet-activating factor receptor antagonist. J Pharmacol Exp Ther. 1991 Oct;259(1):44-51.
• [4] In vitro inhibitory effect of SR 27417, a potent platelet-activating factor (PAF) receptor antagonist, on the PAF-induced bovine platelet aggregation. Vet Res. 2000 Mar-Apr;31(2):267-72.
• [5] Therapeutic target database update 2012: a resource for facilitating target-oriented drug discovery. Nucleic Acids Res. 2012 Jan;40(Database issue):D1128-36.
• [6] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [7] Designed multiple ligands. An emerging drug discovery paradigm. J Med Chem. 2005 Oct 20;48(21):6523-43.
• [8] Amino acid residues critical for endoplasmic reticulum export and trafficking of platelet-activating factor receptor. J Biol Chem. 2010 Feb 19;285(8):5931-40.
• [9] Anti-inflammatory activities of LDP-392, a dual PAF receptor antagonist and 5-lipoxygenase inhibitor. Pharmacol Res. 2001 Sep;44(3):213-20.
• [10] Lexipafant and acute pancreatitis: a critical appraisal of the clinical trials.Eur J Surg.2002;168(4):215-9.
• [11] Effects of YM264, a novel PAF antagonist, on puromycin aminonucleoside-induced nephropathy in the rat. Biochem Biophys Res Commun. 1991 Apr 30;176(2):781-5.
• [12] The intestinal anti-inflammatory effect of dersalazine sodium is related to a down-regulation in IL-17 production in experimental models of rodent colitis. Br J Pharmacol. 2012 February; 165(3): 729-740.
• [13] Clinical pipeline report, company report or official report of 60 Degrees Pharmaceuticals.
• [14] Sch 37370: a new drug combining antagonism of platelet-activating factor (PAF) with antagonism of histamine. Agents Actions Suppl. 1991;34:313-21.
• [15] Platelet-activating factor antagonist BN 50730 attenuates hypoxic-ischemic brain injury in neonatal rats. Pediatr Res. 2001 Jun;49(6):804-11.