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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

Molecular Formula C26H24N6O2
Molecular Weight 452.5078
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment: Description was created based on several sources, including http://kadmon.com/research-development/pipeline/ http://en.pharmacodia.com/web/drug/1_1994.html

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.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
60.0 nM [IC50]
Target ID: Q9HBE4
Gene ID: 59067.0
Gene Symbol: IL21
Target Organism: Homo sapiens (Human)
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
128.4 ng/mL
5 mg/kg single, oral
dose: 5 mg/kg
route of administration: Oral
experiment type: SINGLE
co-administered:
KD-025 FREE BASE plasma
Rattus norvegicus
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
48.7 μg × min/mL
5 mg/kg single, oral
dose: 5 mg/kg
route of administration: Oral
experiment type: SINGLE
co-administered:
KD-025 FREE BASE plasma
Rattus norvegicus
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
353.4 h
5 mg/kg single, oral
dose: 5 mg/kg
route of administration: Oral
experiment type: SINGLE
co-administered:
KD-025 FREE BASE plasma
Rattus norvegicus
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
Doses

Doses

DosePopulationAdverse events​
400 mg 2 times / day multiple, oral
Highest studied dose
Dose: 400 mg, 2 times / day
Route: oral
Route: multiple
Dose: 400 mg, 2 times / day
Sources: Page: p.3811
unhealthy
n = 7
Health Status: unhealthy
Condition: psoriasis
Sex: M+F
Food Status: UNKNOWN
Population Size: 7
Sources: Page: p.3811
Disc. AE: ALT increased, AST increased...
AEs leading to
discontinuation/dose reduction:
ALT increased (33.3%)
AST increased (33.3%)
Sources: Page: p.3811
AEs

AEs

AESignificanceDosePopulation
ALT increased 33.3%
Disc. AE
400 mg 2 times / day multiple, oral
Highest studied dose
Dose: 400 mg, 2 times / day
Route: oral
Route: multiple
Dose: 400 mg, 2 times / day
Sources: Page: p.3811
unhealthy
n = 7
Health Status: unhealthy
Condition: psoriasis
Sex: M+F
Food Status: UNKNOWN
Population Size: 7
Sources: Page: p.3811
AST increased 33.3%
Disc. AE
400 mg 2 times / day multiple, oral
Highest studied dose
Dose: 400 mg, 2 times / day
Route: oral
Route: multiple
Dose: 400 mg, 2 times / day
Sources: Page: p.3811
unhealthy
n = 7
Health Status: unhealthy
Condition: psoriasis
Sex: M+F
Food Status: UNKNOWN
Population Size: 7
Sources: Page: p.3811
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Selective oral ROCK2 inhibitor down-regulates IL-21 and IL-17 secretion in human T cells via STAT3-dependent mechanism.
2014 Nov 25
Patents

Patents

Sample Use Guides

KD025 dose of 200 mg daily for 4 weeks
Route of Administration: Oral
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
Substance Class Chemical
Created
by admin
on Fri Dec 15 19:40:54 GMT 2023
Edited
by admin
on Fri Dec 15 19:40:54 GMT 2023
Record UNII
834YJF89WO
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
Belumosudil
INN   USAN  
Official Name English
ROCK2 INHIBITOR KD025
Common Name English
belumosudil [INN]
Common Name English
KD-025
Code English
ACETAMIDE, 2-(3-(4-(1H-INDAZOL-5-YLAMINO)-2-QUINAZOLINYL)PHENOXY)-N-(1-METHYLETHYL)-
Systematic Name English
BELUMOSUDIL [USAN]
Common Name English
2-(3-(4-((1H-INDAZOL-5-YL)AMINO)QUINAZOLIN-2-YL)PHENOXY)-N-ISOPROPYLACETAMIDE
Systematic Name English
SLX-2119 FREE BASE
Common Name English
Belumosudil [WHO-DD]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C61074
Created by admin on Fri Dec 15 19:40:54 GMT 2023 , Edited by admin on Fri Dec 15 19:40:54 GMT 2023
FDA ORPHAN DRUG 760520
Created by admin on Fri Dec 15 19:40:54 GMT 2023 , Edited by admin on Fri Dec 15 19:40:54 GMT 2023
Code System Code Type Description
RXCUI
2564025
Created by admin on Fri Dec 15 19:40:54 GMT 2023 , Edited by admin on Fri Dec 15 19:40:54 GMT 2023
PRIMARY
INN
11343
Created by admin on Fri Dec 15 19:40:54 GMT 2023 , Edited by admin on Fri Dec 15 19:40:54 GMT 2023
PRIMARY
DAILYMED
834YJF89WO
Created by admin on Fri Dec 15 19:40:54 GMT 2023 , Edited by admin on Fri Dec 15 19:40:54 GMT 2023
PRIMARY
WIKIPEDIA
Belumosudil
Created by admin on Fri Dec 15 19:40:54 GMT 2023 , Edited by admin on Fri Dec 15 19:40:54 GMT 2023
PRIMARY
PUBCHEM
11950170
Created by admin on Fri Dec 15 19:40:54 GMT 2023 , Edited by admin on Fri Dec 15 19:40:54 GMT 2023
PRIMARY
EPA CompTox
DTXSID80238425
Created by admin on Fri Dec 15 19:40:54 GMT 2023 , Edited by admin on Fri Dec 15 19:40:54 GMT 2023
PRIMARY
NCI_THESAURUS
C128786
Created by admin on Fri Dec 15 19:40:54 GMT 2023 , Edited by admin on Fri Dec 15 19:40:54 GMT 2023
PRIMARY
CAS
911417-87-3
Created by admin on Fri Dec 15 19:40:54 GMT 2023 , Edited by admin on Fri Dec 15 19:40:54 GMT 2023
PRIMARY
SMS_ID
100000183980
Created by admin on Fri Dec 15 19:40:54 GMT 2023 , Edited by admin on Fri Dec 15 19:40:54 GMT 2023
PRIMARY
USAN
FG-181
Created by admin on Fri Dec 15 19:40:54 GMT 2023 , Edited by admin on Fri Dec 15 19:40:54 GMT 2023
PRIMARY
FDA UNII
834YJF89WO
Created by admin on Fri Dec 15 19:40:54 GMT 2023 , Edited by admin on Fri Dec 15 19:40:54 GMT 2023
PRIMARY
Related Record Type Details
METABOLIC ENZYME -> INHIBITOR
Inhibits at clinically relevant concentrations.
SALT/SOLVATE -> PARENT
METABOLIC ENZYME -> INHIBITOR
Inhibits at clinically relevant concentrations.
BINDER->LIGAND
EXCRETED UNCHANGED
FECAL
CUMULATIVE EXCRETION
URINE
METABOLIC ENZYME -> SUBSTRATE
Based on in vitro assessment, CYP3A4 (41.9%) was the predominant cytochrome P450 (CYP) isoform responsible for the metabolism of belumosudil.
MAJOR
SALT/SOLVATE -> PARENT
TRANSPORTER -> INHIBITOR
Inhibits at clinically relevant concentrations.
METABOLIC ENZYME -> SUBSTRATE
Based on in vitro assessment, CYP3A4 (41.9%) was the predominant cytochrome P450 (CYP) isoform responsible for the metabolism of belumosudil although CYP2D6 (21.7%), CYP2C8 (14.2%), CYP1A2 (<5%), CYP2C19 (<5%), and UGT1A9 may also contribute to a lesser extent
TRANSPORTER -> SUBSTRATE
TRANSPORTER -> INHIBITOR
Inhibits at clinically relevant concentrations.
METABOLIC ENZYME -> INHIBITOR
Inhibits at clinically relevant concentrations.
METABOLIC ENZYME -> SUBSTRATE
Based on in vitro assessment, CYP3A4 (41.9%) was the predominant cytochrome P450 (CYP) isoform responsible for the metabolism of belumosudil although CYP2D6 (21.7%), CYP2C8 (14.2%), CYP1A2 (<5%), CYP2C19 (<5%), and UGT1A9 may also contribute to a lesser extent
EXCRETED UNCHANGED
FECAL
CUMULATIVE EXCRETION
FECAL
METABOLIC ENZYME -> INHIBITOR
Inhibits at clinically relevant concentrations.
TARGET -> INHIBITOR
Inhibits signal transducer and activator of transcription 3 (STAT3) phosphorylation. Shifts T helper 17 (Th17)/T regulatory (Treg) balance towards the Treg phenotype
IC50
TRANSPORTER -> INHIBITOR
Inhibits at clinically relevant concentrations.
METABOLIC ENZYME -> INHIBITOR
Inhibits at clinically relevant concentrations.
Related Record Type Details
METABOLITE LESS ACTIVE -> PARENT
MAJOR
FECAL; PLASMA; URINE
METABOLITE ACTIVE -> PARENT
MINOR
PLASMA
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC
Volume of Distribution PHARMACOKINETIC