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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=CC5=C(NN=C5)C=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.

CNS Activity

Originator

Approval Year

2021
460
Targets

Targets

Primary TargetPharmacologyConditionPotency
Inhibitor
8504
 60.0 nM [IC50]
Inhibitor
8504
Interleukin-21
3
Target ID: Q9HBE4
Gene ID: 59067.0
Gene Symbol: IL21
Target Organism: Homo sapiens (Human)
Inhibitor
8504
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Phase II
1147
Unknown

Approved Use

Unknown
Primary
Phase II
1147
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
3140 ng/mL
CLINICAL TRIAL
https://clinicaltrials.gov/study/NCT02317627?tab=results
400 mg single, oral
dose: 400 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
KD-025 FREE BASE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
1770 ng/mL
CLINICAL TRIAL
https://clinicaltrials.gov/study/NCT02317627?tab=results
200 mg 2 times / day multiple, oral
dose: 200 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
KD-025 FREE BASE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
16200 ng × h/mL
CLINICAL TRIAL
https://clinicaltrials.gov/study/NCT02317627?tab=results
400 mg single, oral
dose: 400 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
KD-025 FREE BASE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
9150 ng × h/mL
CLINICAL TRIAL
https://clinicaltrials.gov/study/NCT02317627?tab=results
200 mg 2 times / day multiple, oral
dose: 200 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
KD-025 FREE BASE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
8 h
CLINICAL TRIAL
https://clinicaltrials.gov/study/NCT02317627?tab=results
400 mg single, oral
dose: 400 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
KD-025 FREE BASE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
5.13 h
CLINICAL TRIAL
https://clinicaltrials.gov/study/NCT02317627?tab=results
200 mg 2 times / day multiple, oral
dose: 200 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
KD-025 FREE BASE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
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:
https://pubmed.ncbi.nlm.nih.gov/28389592
unhealthy
Health Status: unhealthy
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/28389592
Disc. AE: ALT increased, AST increased...
AEs leading to
discontinuation/dose reduction:
ALT increased (33.3%)
AST increased (33.3%)
Sources:
https://pubmed.ncbi.nlm.nih.gov/28389592
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:
https://pubmed.ncbi.nlm.nih.gov/28389592
unhealthy
Health Status: unhealthy
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/28389592
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:
https://pubmed.ncbi.nlm.nih.gov/28389592
unhealthy
Health Status: unhealthy
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/28389592
Sourcing

Sourcing

Vendor/AggregatorIDURL
1PlusChem LLC
1P003AXB
https://www.1pchem.com/search?query=1P003AXB
AChemBlock
L13971
http://www.achemblock.com/catalogsearch/result/?q=L13971
AK Scientific
4050AH
https://aksci.com/item_detail.php?cat=4050AH
Ambeed
A255643
http://www.ambeed.com/search/Search.html?keyword=A255643
ApexBio Technology
A3825
https://www.apexbt.com/catalogsearch/result/?q=A3825
AstaTech
42507
http://astatechinc.com/CPSResult.php?CRNO=42507
Axon MedChem
2780
https://www.axonmedchem.com/product/2780
BLD Pharm
BD448309
http://www.bldpharm.com/search/Search.html?keyword=BD448309
Cayman Chemical
17055
http://www.caymanchem.com/app/template/Product.vm/catalog/17055
Chem Scene
CS-0776
http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0776
ChemShuttle
152129
https://www.chemshuttle.com/catalogsearch/result/?q=152129
Combi-Blocks
QV-8526
http://www.combi-blocks.com/cgi-bin/find.cgi?QV-8526
eMolecules
44811418
https://orderbb.emolecules.com/search/#?query=44811418
Excenen
EX-A2314
http://www.excenen.com/searchresultlist.php?id=EX-A2314
KeyOrganics
AS-35230
http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-35230
mcule
MCULE-6423720146
https://mcule.com/MCULE-6423720146/
MedChem Express
HY-15307
https://www.medchemexpress.com/search.html?q=HY-15307&ft=&fa=&fp=
MolPort
MolPort-039-139-806
https://www.molport.com/shop/molecule-link/MolPort-039-139-806
MuseChem
I005432
https://www.musechem.com/product/I005432.html
Selleck Chemicals
S7936
http://www.selleckchem.com/search.html?searchDTO.searchParam=S7936
ShangHai Biochempartner
BCP15921
http://www.biochempartner.com/search_BCP15921
PubMed

PubMed

TitleDatePubMed
ROCK2 signaling is required to induce a subset of T follicular helper cells through opposing effects on STATs in autoimmune settings.
2016-07-19
Targeted Rho-associated kinase 2 inhibition suppresses murine and human chronic GVHD through a Stat3-dependent mechanism.
2016-04-28
Selective oral ROCK2 inhibitor down-regulates IL-21 and IL-17 secretion in human T cells via STAT3-dependent mechanism.
2014-11-25
Patents

Patents

WO2014055996A2
3

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
Substance Class Chemical
Created
by admin
on Mon Mar 31 19:53:16 GMT 2025
Edited
by admin
on Mon Mar 31 19:53:16 GMT 2025
Record UNII
834YJF89WO
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
KD-025
Preferred Name English
Belumosudil
INN   USAN  
Official Name English
ROCK2 INHIBITOR KD025
Common Name English
belumosudil [INN]
Common Name 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 Mon Mar 31 19:53:16 GMT 2025 , Edited by admin on Mon Mar 31 19:53:16 GMT 2025
FDA ORPHAN DRUG 760520
Created by admin on Mon Mar 31 19:53:16 GMT 2025 , Edited by admin on Mon Mar 31 19:53:16 GMT 2025
Code System Code Type Description
RXCUI
2564025
Created by admin on Mon Mar 31 19:53:16 GMT 2025 , Edited by admin on Mon Mar 31 19:53:16 GMT 2025
PRIMARY
INN
11343
Created by admin on Mon Mar 31 19:53:16 GMT 2025 , Edited by admin on Mon Mar 31 19:53:16 GMT 2025
PRIMARY
DAILYMED
834YJF89WO
Created by admin on Mon Mar 31 19:53:16 GMT 2025 , Edited by admin on Mon Mar 31 19:53:16 GMT 2025
PRIMARY
WIKIPEDIA
Belumosudil
Created by admin on Mon Mar 31 19:53:16 GMT 2025 , Edited by admin on Mon Mar 31 19:53:16 GMT 2025
PRIMARY
PUBCHEM
11950170
Created by admin on Mon Mar 31 19:53:16 GMT 2025 , Edited by admin on Mon Mar 31 19:53:16 GMT 2025
PRIMARY
EPA CompTox
DTXSID80238425
Created by admin on Mon Mar 31 19:53:16 GMT 2025 , Edited by admin on Mon Mar 31 19:53:16 GMT 2025
PRIMARY
NCI_THESAURUS
C128786
Created by admin on Mon Mar 31 19:53:16 GMT 2025 , Edited by admin on Mon Mar 31 19:53:16 GMT 2025
PRIMARY
CAS
911417-87-3
Created by admin on Mon Mar 31 19:53:16 GMT 2025 , Edited by admin on Mon Mar 31 19:53:16 GMT 2025
PRIMARY
SMS_ID
100000183980
Created by admin on Mon Mar 31 19:53:16 GMT 2025 , Edited by admin on Mon Mar 31 19:53:16 GMT 2025
PRIMARY
USAN
FG-181
Created by admin on Mon Mar 31 19:53:16 GMT 2025 , Edited by admin on Mon Mar 31 19:53:16 GMT 2025
PRIMARY
FDA UNII
834YJF89WO
Created by admin on Mon Mar 31 19:53:16 GMT 2025 , Edited by admin on Mon Mar 31 19:53:16 GMT 2025
PRIMARY
Related Record Type Details
CYTOCHROME P450 1A2
METABOLIC ENZYME -> INHIBITOR
Inhibits at clinically relevant concentrations.
Structure of Belumosudil mesylate
SALT/SOLVATE -> PARENT
URIDINE DIPHOSPHATE GLUCURONOSYLTRANSFERASE 1A9
METABOLIC ENZYME -> INHIBITOR
Inhibits at clinically relevant concentrations.
PLASMA PROTEIN FRACTION (HUMAN)
BINDER->LIGAND
Structure of Belumosudil
EXCRETED UNCHANGED
FECAL
Structure of Belumosudil
CUMULATIVE EXCRETION
URINE
CYTOCHROME P450 3A4
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
Structure of BELUMOSUDIL TRIFLUOROACETATE
SALT/SOLVATE -> PARENT
OATP1B1
TRANSPORTER -> INHIBITOR
Inhibits at clinically relevant concentrations.
CYTOCHROME P450 2C8
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
MULTIDRUG RESISTANCE PROTEIN 1
TRANSPORTER -> SUBSTRATE
MULTIDRUG RESISTANCE PROTEIN 1
TRANSPORTER -> INHIBITOR
Inhibits at clinically relevant concentrations.
URIDINE DIPHOSPHATE GLUCURONOSYLTRANSFERASE 1A1
METABOLIC ENZYME -> INHIBITOR
Inhibits at clinically relevant concentrations.
CYTOCHROME P450 2D6
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
Structure of Belumosudil
EXCRETED UNCHANGED
FECAL
Structure of Belumosudil
CUMULATIVE EXCRETION
FECAL
CYTOCHROME P450 2D6
METABOLIC ENZYME -> INHIBITOR
Inhibits at clinically relevant concentrations.
RHO-ASSOCIATED PROTEIN KINASE 2
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
ATP-BINDING CASSETTE SUB-FAMILY G MEMBER 2
TRANSPORTER -> INHIBITOR
Inhibits at clinically relevant concentrations.
CYTOCHROME P450 2C19
METABOLIC ENZYME -> INHIBITOR
Inhibits at clinically relevant concentrations.
Related Record Type Details
Structure of 2-(3-(4-((1H-INDAZOL-5-YL)AMINO)QUINAZOLIN-2-YL)PHENOXY)ACETIC ACID
METABOLITE LESS ACTIVE -> PARENT
MAJOR
FECAL; PLASMA; URINE
Structure of 2-(3-(4-((1H-INDAZOL-5-YL)AMINO)QUINAZOLIN-2-YL)PHENOXY)ACETAMIDE
METABOLITE ACTIVE -> PARENT
MINOR
PLASMA
Related Record Type Details
Structure of Belumosudil
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC
Volume of Distribution PHARMACOKINETIC
NIH
NCATS
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