VIDUPIPRANT

Details

Stereochemistry	ACHIRAL
Molecular Formula	C28H27Cl2FN2O6S
Molecular Weight	609.493
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(C)(C)NC(=O)C1=CC(NS(=O)(=O)C2=C(Cl)C=C(C=C2)C3CC3)=C(OC4=CC(F)=C(CC(O)=O)C=C4Cl)C=C1

InChI

InChIKey=PFWVGKROPKKEDW-UHFFFAOYSA-N

InChI=1S/C28H27Cl2FN2O6S/c1-28(2,3)32-27(36)17-6-8-23(39-24-14-21(31)18(11-19(24)29)13-26(34)35)22(12-17)33-40(37,38)25-9-7-16(10-20(25)30)15-4-5-15/h6-12,14-15,33H,4-5,13H2,1-3H3,(H,32,36)(H,34,35)

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/22930276 | https://www.ncbi.nlm.nih.gov/pubmed/24900313 | https://www.ncbi.nlm.nih.gov/pubmed/23174659

Vidupiprant, also known as AMG 853, is an orally bioavailable and potent dual antagonist of the D-prostanoid and chemoattractant receptor-homologous molecule expressed on T helper 2 cells receptors. Vidupiprant inhibits PGD2-induced down modulation of CRTH2 on CD16- granulocytes in human whole blood as well as PGD2-induced cAMP response in platelets. It inhibits PGD2-induced airway constriction in vivo. Also inhibits BRD4 (Kd = 170 nM). AMG 853 as an add-on to inhaled corticosteroid therapy demonstrated no associated risks but was not effective at improving asthma symptoms or lung function in patients with inadequately controlled moderate-to-severe asthma. AMG 853 has been discontinued due to poor efficacy.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
G protein-coupled receptor 44 7 Target ID: CHEMBL5071 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24900313	Antagonist 2778		3.0 nM [IC50]
Prostanoid DP receptor 15 Target ID: CHEMBL4427 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24900313	Antagonist 2778		35.0 nM [IC50]

PubMed

Title	Date	PubMed
Conformational isomerism in solid state of AMG 853--structure studies using solid-state nuclear magnetic resonance and X-ray diffraction.	2015 Jul	25912152
Structure-based design of allosteric calpain-1 inhibitors populating a novel bioactivity space.	2018 Sep 5	30195237

Patents

Sample Use Guides

In Vivo Use Guide

Adults with moderate-to-severe asthma were randomized to placebo; 5, 25, or 100 mg of oral Vidupiprant (AMG 853) twice daily; or 200 mg of AMG 853 once daily for 12 weeks.

Route of Administration: Oral

In Vitro Use Guide

Vidupiprant inhibited the full-length calpain-1 complex with a high potency (IC50 = 7.5 uM). Vidupiprant is a potent dual CRTH2 and prostaglandin D2 (PGD2) receptor antagonist (IC50 values are 8 and 35 nM, respectively in plasma).

Name

Type

Language

VIDUPIPRANT

Official Name

English

VIDUPIPRANT [USAN]

Common Name

English

(4-(4-(TERT-BUTYLCARBAMOYL)-2-(2-CHLORO-4-CYCLOPROPYLBENZENESULFONAMIDO)PHENOXY)-5-CHLORO-2-FLUOROPHENYL)ACETIC ACID

Systematic Name

English

AMG853

Code

English

BENZENEACETIC ACID, 5-CHLORO-4-(2-(((2-CHLORO-4-CYCLOPROPYLPHENYL)SULFONYL)AMINO)-4- (((1,1-DIMETHYLETHYL)AMINO)CARBONYL)PHENOXY)-2-FLUORO-

Common Name

English

Vidupiprant [WHO-DD]

Common Name

English

2-(4-(4-(TERT-BUTYLCARBAMOYL)-2-(2-CHLORO-4-CYCLOPROPYLBENZENESULFONAMIDO)PHENOXY)-5-CHLORO-2-FLUOROPHENYL)ACETIC ACID

Systematic Name

English

vidupiprant [INN]

Common Name

English

AMG-853

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C29712