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Details

Stereochemistry ABSOLUTE
Molecular Formula C41H52N4O4S.CH4O3S
Molecular Weight 793.047
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of CENICRIVIROC MESYLATE

SMILES

CS(O)(=O)=O.CCCCOCCOC1=CC=C(C=C1)C2=CC3=C(C=C2)N(CC(C)C)CCCC(=C3)C(=O)NC4=CC=C(C=C4)[S@@+]([O-])CC5=CN=CN5CCC

InChI

InChIKey=IXPBPUPDRDCRSY-YLZLUMLXSA-N
InChI=1S/C41H52N4O4S.CH4O3S/c1-5-7-22-48-23-24-49-38-15-10-32(11-16-38)33-12-19-40-35(25-33)26-34(9-8-21-44(40)28-31(3)4)41(46)43-36-13-17-39(18-14-36)50(47)29-37-27-42-30-45(37)20-6-2;1-5(2,3)4/h10-19,25-27,30-31H,5-9,20-24,28-29H2,1-4H3,(H,43,46);1H3,(H,2,3,4)/b34-26+;/t50-;/m0./s1

HIDE SMILES / InChI

Description

Cenicriviroc (also referred to as TBR-652 and TAK-652) is an orally active, potent inhibitor of ligand binding to C-C chemokine receptor type 2 (CCR2) and C-C chemokine receptor type 5 (CCR5). Cenicriviroc does not inhibit ligand binding to CCR1 (an alternative target of CCR5 ligands). The mean half-life in healthy volunteers is 35 to 40 hours, which allows daily dosing of the drug. Due to its CCR5 blocking activity, Cenicriviroc has initially been tested as a drug against CCR5-tropic HIV infection. In a double-blind placebo-controlled trial involving 54 HIV infected participants, Cenicriviroc monotherapy at different doses (25, 50, 75, 100, or 150 mg) led to a dose-dependent reduction in HIV-1 RNA levels and concomitant increases in circulating levels of the CCR2 ligand monocyte chemoattractant protein 1 (MCP-1, or CCL2), suggesting potent CCR2 and CCR5 inhibition in vivo. According to clinical trials, Cenicriviroc is a very safe drug with a wide therapeutic range and fairly low pharmacokinetic variability. In animal models of liver diseases, Cenicriviroc potently inhibits macrophage accumulation in the liver and ameliorates fibrosis. In a phase 2b clinical trial on 289 patients with NASH and fibrosis, Cenicriviroc consistently demonstrated liver fibrosis improvement after 1 year of therapy and had an excellent safety profile.

Originator

Approval Year

Targets

Primary TargetPharmacologyConditionPotency
3.1 nM [IC50]
2.9 nM [IC50]

PubMed

Sample Use Guides

In Vivo Use Guide
150 mg/day cenicriviroc
Route of Administration: Oral