Details of the Drug

General Information of Drug (ID: DM2NTJY)

Drug Name

R-68151

Synonyms

1-Ethyl-3-{4-[4-(4-hydroxy-phenyl)-piperazin-1-yl]-phenyl}-5,5-dimethyl-2-thioxo-imidazolidin-4-one; 5-Lipoxygenase-In-1; R 68151; CHEMBL85599; 138331-04-1; AC1L30HG; SCHEMBL13696698; DTXSID10160583; BDBM50006793; HY-U00308; CS-7300; (1-Ethyl-3(4-(4-(4-hydroxyphenyl)-1-piperazinyl)phenyl)-5-dimethyl)-2-thioxo-4-imidazolidinone; 1-ethyl-3-[4-[4-(4-hydroxyphenyl)piperazin-1-yl]phenyl]-5,5-dimethyl-2-sulfanylideneimidazolidin-4-one; M55551

Indication

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

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

424.6

Topological Polar Surface Area (xlogp)

3.8

Rotatable Bond Count (rotbonds)

4

Hydrogen Bond Donor Count (hbonddonor)

1

Hydrogen Bond Acceptor Count (hbondacc)

5

Chemical Identifiers

Formula: C23H28N4O2S
IUPAC Name: 1-ethyl-3-[4-[4-(4-hydroxyphenyl)piperazin-1-yl]phenyl]-5,5-dimethyl-2-sulfanylideneimidazolidin-4-one
Canonical SMILES: CCN1C(=S)N(C(=O)C1(C)C)C2=CC=C(C=C2)N3CCN(CC3)C4=CC=C(C=C4)O
InChI: InChI=1S/C23H28N4O2S/c1-4-26-22(30)27(21(29)23(26,2)3)19-7-5-17(6-8-19)24-13-15-25(16-14-24)18-9-11-20(28)12-10-18/h5-12,28H,4,13-16H2,1-3H3
InChIKey: AHWDHLCCXRVAIC-UHFFFAOYSA-N

Cross-matching ID

PubChem CID: 132150
CAS Number: 138331-04-1
TTD ID: D0G5GJ

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	Inhibitor	[2], [3]
Coagulation factor Xa (F10)	TTCIHJA	FA10_HUMAN	Inhibitor	[4]

------------------------------------------------------------------------------------

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This Drug

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
Arachidonate 5-lipoxygenase (5-LOX)	DTT	ALOX5	4.15E-01	-0.06	-0.15

Molecular Expression Atlas (MEA)

MEA Detail

Jump to Detail Molecular Expression Atlas of This Drug

References

1	Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800003630)
2	Preview of potential therapeutic applications of leukotriene B4 inhibitors in dermatology. Skin Pharmacol Appl Skin Physiol. 2000 Sep-Oct;13(5):235-45.
3	Topical R-85355, a potent and selective 5-lipoxygenase inhibitor, fails to improve psoriasis. Skin Pharmacol. 1996;9(5):307-11.
4	Synthesis and evaluation of 1-arylsulfonyl-3-piperazinone derivatives as a factor Xa inhibitor II. Substituent effect on biological activities. Chem Pharm Bull (Tokyo). 2002 Sep;50(9):1187-94.
5	5-lipoxygenase inhibitor zileuton attenuates ischemic brain damage: involvement of matrix metalloproteinase 9. Neurol Res. 2009 Oct;31(8):848-52.
6	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.
7	Anti-inflammatory and anti-arthritic activities of silymarin acting through inhibition of 5-lipoxygenase. Phytomedicine. 2000 Mar;7(1):21-4.
8	Phenidone protects the nigral dopaminergic neurons from LPS-induced neurotoxicity. Neurosci Lett. 2008 Nov 7;445(1):1-6.
9	Simple analogues of anthralin: unusual specificity of structure and antiproliferative activity. J Med Chem. 1997 Nov 7;40(23):3773-80.
10	Treatment with 5-lipoxygenase inhibitor VIA-2291 (Atreleuton) in patients with recent acute coronary syndrome. Circ Cardiovasc Imaging. 2010 May;3(3):298-307.
11	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.
12	FPL 62064, a topically active 5-lipoxygenase/cyclooxygenase inhibitor. Agents Actions. 1990 Jun;30(3-4):432-42.
13	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.
14	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.
15	Pfizer. Product Development Pipeline. March 31 2009.
16	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
17	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. (Target id: 2359).
18	2017 FDA drug approvals.Nat Rev Drug Discov. 2018 Feb;17(2):81-85.
19	Company report (Portola)
20	Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
21	Serum zinc concentrations: contamination from laboratory equipment. JPEN J Parenter Enteral Nutr. 1979 May-Jun;3(3):179-81.
22	Biochemistry and clinical pharmacology of new anticoagulant agents. Pathophysiol Haemost Thromb. 2002 Sep-Dec;32(5-6):218-24.
23	Effect of factor X inhibition on coagulation activation and cytokine induction in human systemic inflammation. J Infect Dis. 2002 Nov 1;186(9):1270-6.
24	Haemophilia B: Christmas disease. Expert Opin Pharmacother. 2005 Aug;6(9):1517-24.