ISRAPAFANT

Details

Stereochemistry	RACEMIC
Molecular Formula	C28H29ClN4S
Molecular Weight	489.075
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(C)CC1=CC=C(CCC2=CC3=C(S2)N4C(C)=NN=C4C(C)N=C3C5=C(Cl)C=CC=C5)C=C1

InChI

InChIKey=RMSWMRJVUJSDGN-UHFFFAOYSA-N

InChI=1S/C28H29ClN4S/c1-17(2)15-21-11-9-20(10-12-21)13-14-22-16-24-26(23-7-5-6-8-25(23)29)30-18(3)27-32-31-19(4)33(27)28(24)34-22/h5-12,16-18H,13-15H2,1-4H3

HIDE SMILES / InChI

Molecular Formula	C28H29ClN4S
Molecular Weight	489.075
Charge	0
Count

Stereochemistry	RACEMIC
Additional Stereochemistry	No
Defined Stereocenters	0 / 1
E/Z Centers	0
Optical Activity	( + / - )

Description
Sources: http://www.medkoo.com/products/10704
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/10579457 https://www.ncbi.nlm.nih.gov/pubmed/2093935

Israpafant (also known as Y-24180) is a drug which acts as a selective antagonist for the platelet-activating factor receptor, and was originally developed for the treatment of asthma. Its chemical structure is a thienotriazolodiazepines, closely related to the sedative benzodiazepine derivative etizolam. However, israpafant binds far more tightly to the platelet-activating factor receptor, with an IC50 of 0.84nM for inhibiting PAF-induced human platelet aggregation, while it binds only weakly to benzodiazepine receptors, with a Ki of 3680nM. Israpafant has been found to inhibit the activation of eosinophil cells and consequently delays the development of immune responses. It has also been shown to have anti-nephrotoxic properties and to mobilize calcium transport.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Interleukin-5 3 Target ID: CHEMBL1169600 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10880261	Inhibitor 8297
Platelet activating factor receptor 20 Target ID: CHEMBL250 Sources: https://www.ncbi.nlm.nih.gov/pubmed/2093935	Antagonist 2778		0.84 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Asthma 241 Sources: http://adisinsight.springer.com/drugs/800001699	Primary		Phase III 656	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Molecular cloning and expression of platelet-activating factor receptor from human leukocytes.	1991 Oct 25	1657923

Patents

Sample Use Guides

In Vivo Use Guide

20 mg twice a day was orally administered for 2 wk

Route of Administration: Oral

In Vitro Use Guide

Israpafant (1-10 uM) caused a rapid and sustained [Ca2+]i rise in a concentration-dependent manner in human prostate cancer cells. 0.1-10 uM Israpafant inhibited cell proliferation in a concentration-dependent manner.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 16:38:43 GMT 2023` Edited by `admin` on `Fri Dec 15 16:38:43 GMT 2023`
Record UNII	O3MCV749SW
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

ISRAPAFANT

Official Name

English

(±)-4-(O-CHLOROPHENYL)-2-(P-ISOBUTYLPHENETHYL)-6,9-DIMETHYL-6H-THIENO(3,2-F)-S-TRIAZOLO(4,3-A)(1,4)DIAZEPINE

Common Name

English

ISRAPAFANT [MI]

Common Name

English

Israpafant [WHO-DD]

Common Name

English

ISRAPAFANT [JAN]

Common Name

English

israpafant [INN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C1327