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Details

Stereochemistry ACHIRAL
Molecular Formula C26H24N6O2
Molecular Weight 452.5078
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of Belumosudil

SMILES

CC(C)NC(=O)COC1=CC=CC(=C1)C2=NC3=C(C=CC=C3)C(NC4=CC=C5NN=CC5=C4)=N2

InChI

InChIKey=GKHIVNAUVKXIIY-UHFFFAOYSA-N
InChI=1S/C26H24N6O2/c1-16(2)28-24(33)15-34-20-7-5-6-17(13-20)25-30-23-9-4-3-8-21(23)26(31-25)29-19-10-11-22-18(12-19)14-27-32-22/h3-14,16H,15H2,1-2H3,(H,27,32)(H,28,33)(H,29,30,31)

HIDE SMILES / InChI

Description

KD025 is an orally available, selective small molecule inhibitor of ROCK2 (Rho-associated coiled-coil kinase 2), a molecular target in multiple autoimmune, fibrotic and neurodegenerative diseases. KD025 is the only ROCK2-specific inhibitor in the clinical trials. KD025 down-regulates the IL-17 and IL-21 secretion in human PBMCs, and leads to down-regulation of STAT3 phosphorylation, IRF4, and RORγt expression in CD4+ T cells. Kadmon Pharmaceuticals initiated phase II clinical trials of KD025 for the treatment of Graft-versus-host disease; Idiopathic pulmonary fibrosis; Plaque psoriasis.

CNS Activity

Originator

Approval Year

Targets

Primary TargetPharmacologyConditionPotency
60.0 nM [IC50]

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown
Primary
Unknown

Cmax

ValueDoseCo-administeredAnalytePopulation
128.4 ng/mL
5 mg/kg single, oral
KD-025 FREE BASE plasma
Rattus norvegicus

AUC

ValueDoseCo-administeredAnalytePopulation
48.7 μg × min/mL
5 mg/kg single, oral
KD-025 FREE BASE plasma
Rattus norvegicus

T1/2

ValueDoseCo-administeredAnalytePopulation
353.4 h
5 mg/kg single, oral
KD-025 FREE BASE plasma
Rattus norvegicus

Doses

AEs

PubMed

Patents

Sample Use Guides

In Vivo Use Guide
KD025 dose of 200 mg daily for 4 weeks
Route of Administration: Oral
In Vitro Use Guide
KD025 selectively inhibited ROCK2 with IC50 values ~60 nmol/L, but had little effect on ROCK1 enzymatic activity at concentrations up to 10 umol/L in a recombinant enzyme system