Details of the Drug

General Information of Drug (ID: DM1NCUY)

• Drug Name: CMI-392
• Synonyms: LDP-392; 3-[2-[2-(4-Chlorophenylsulfanyl)ethoxy]-3-methoxy-5-[trans-5-(3,4,5-trimethoxyphenyl)tetrahydrofuran-2-yl]benzyl]-1-hydroxy-1-methylurea

Indication

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

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 2:
  Molecular Weight (mw); 633.2
  Topological Polar Surface Area (xlogp); 4.9
  Rotatable Bond Count (rotbonds); 13
  Hydrogen Bond Donor Count (hbonddonor); 2
  Hydrogen Bond Acceptor Count (hbondacc); 9
• Chemical Identifiers:
  Formula: C31H37ClN2O8S
  IUPAC Name: 3-[[2-[2-(4-chlorophenyl)sulfanylethoxy]-3-methoxy-5-[(2S,5S)-5-(3,4,5-trimethoxyphenyl)oxolan-2-yl]phenyl]methyl]-1-hydroxy-1-methylurea
  Canonical SMILES: CN(C(=O)NCC1=C(C(=CC(=C1)[C@@H]2CC[C@H](O2)C3=CC(=C(C(=C3)OC)OC)OC)OC)OCCSC4=CC=C(C=C4)Cl)O
  InChI: InChI=1S/C31H37ClN2O8S/c1-34(36)31(35)33-18-21-14-19(15-26(37-2)29(21)41-12-13-43-23-8-6-22(32)7-9-23)24-10-11-25(42-24)20-16-27(38-3)30(40-5)28(17-20)39-4/h6-9,14-17,24-25,36H,10-13,18H2,1-5H3,(H,33,35)/t24-,25-/m0/s1
  InChIKey: LZVBMKDVEPGGFK-DQEYMECFSA-N
• Cross-matching ID:
  PubChem CID: 6918268
  TTD ID: D0D5ZV

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Arachidonate 5-lipoxygenase (5-LOX)	TT2J34L	LOX5_HUMAN	Modulator	[1]
Platelet-activating factor receptor (PTAFR)	TTQL5VC	PTAFR_HUMAN	Modulator	[1]

Molecular Expression Atlas of This Drug

• The Studied Disease: Psoriasis vulgaris
• ICD Disease Classification: EA90

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

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• [2] 5-lipoxygenase inhibitor zileuton attenuates ischemic brain damage: involvement of matrix metalloproteinase 9. Neurol Res. 2009 Oct;31(8):848-52.
• [3] Inhibition of leukotriene formation by diethylcarbamazine modifies the acid-base balance in the rabbits with blast injuries of the lungs. Vojnosanit Pregl. 1999 May-Jun;56(3):243-7.
• [4] Anti-inflammatory and anti-arthritic activities of silymarin acting through inhibition of 5-lipoxygenase. Phytomedicine. 2000 Mar;7(1):21-4.
• [5] Phenidone protects the nigral dopaminergic neurons from LPS-induced neurotoxicity. Neurosci Lett. 2008 Nov 7;445(1):1-6.
• [6] Simple analogues of anthralin: unusual specificity of structure and antiproliferative activity. J Med Chem. 1997 Nov 7;40(23):3773-80.
• [7] Treatment with 5-lipoxygenase inhibitor VIA-2291 (Atreleuton) in patients with recent acute coronary syndrome. Circ Cardiovasc Imaging. 2010 May;3(3):298-307.
• [8] The in vitro free radical scavenging activity of tenidap, a new dual cyclo-oxygenase and 5-1ipoxygenase inhibitor. Mediators Inflamm. 1992;1(2):141-3.
• [9] FPL 62064, a topically active 5-lipoxygenase/cyclooxygenase inhibitor. Agents Actions. 1990 Jun;30(3-4):432-42.
• [10] Pharmacological profile of the novel potent antirheumatic 4-(2',4'-difluorobiphenyl-4-yl)-2-methyl-4-oxobutanoic acid. Arzneimittelforschung. 1997 May;47(5):648-52.
• [11] Novel dual cyclooxygenase and lipoxygenase inhibitors targeting hyaluronan-CD44v6 pathway and inducing cytotoxicity in colon cancer cells. Bioorg Med Chem. 2013 May 1;21(9):2551-9.
• [12] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [13] Designed multiple ligands. An emerging drug discovery paradigm. J Med Chem. 2005 Oct 20;48(21):6523-43.
• [14] 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.
• [15] Lexipafant and acute pancreatitis: a critical appraisal of the clinical trials.Eur J Surg.2002;168(4):215-9.
• [16] 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.
• [17] 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.
• [18] Clinical pipeline report, company report or official report of 60 Degrees Pharmaceuticals.
• [19] Sch 37370: a new drug combining antagonism of platelet-activating factor (PAF) with antagonism of histamine. Agents Actions Suppl. 1991;34:313-21.
• [20] 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.
• [21] Platelet-activating factor antagonist BN 50730 attenuates hypoxic-ischemic brain injury in neonatal rats. Pediatr Res. 2001 Jun;49(6):804-11.