Belumosudil

Summary

Belumosudil (CHEMBL2005186) is an approved small molecule (ATC L04AA48) targeting ROCK1 and ROCK2; indicated across 10 conditions including immune system disorder and diffuse scleroderma.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: L04AA48
• Targets: 2 (ROCK1, ROCK2)
• Indications: 10 conditions
• Clinical trials: 31
• Chemistry: 452.5 Da · C26H24N6O2

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL2005186
Name	Belumosudil
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	11950170
ATC	L04AA48
Molecular formula	C26H24N6O2
Molecular weight	452.5
InChIKey	GKHIVNAUVKXIIY-UHFFFAOYSA-N

SMILES: CC(C)NC(=O)COC1=CC=CC(=C1)C2=NC3=CC=CC=C3C(=N2)NC4=CC5=C(C=C4)NN=C5

IUPAC name: 2-[3-[4-(1H-indazol-5-ylamino)quinazolin-2-yl]phenoxy]-N-propan-2-ylacetamide

Also known as: Belumosudil, KD-025, KD025, Rock2 inhibitor kd025, Slx-2119 free base, SID103905007, SLX-2119, SLx-2119, BELUMOSUDIL, BELUMOSUDIL MESYLATE

Parent form; salt/anhydrous children: CHEMBL4802130

Patent coverage: 669 distinct patent families (1,817 SureChEMBL compound mentions), from 4 matched compound structure(s). One matched structure accounts for 1,581 (87%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
ROCK1	Rho associated coiled-coil containing protein kinase 1	Inhibition	4.62	1.4%	Q13464
ROCK2	Rho associated coiled-coil containing protein kinase 2	Inhibition	6.98	1.1%	O75116

Broader ChEMBL bioactivity targets: 10 (assay-derived). Sample: Aurora kinase B, Tyrosine-protein kinase Blk, Dual specificity tyrosine-phosphorylation-regulated kinase 1A, Rho-associated protein kinase 2, Rho-associated protein kinase 1, Casein kinase II subunit alpha, Dual specificity protein kinase CLK4, Dual specificity protein kinase CLK2, Serine/threonine-protein kinase 17A, Serine/threonine-protein kinase 3.

Bioactivity

ChEMBL activities: 37 potent at pChembl ≥ 5 of 45 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
ROCK1	7.62	IC50	24	nM	CHEMBL_ACT_29156706
ROCK1	7.4	Ki	40	nM	CHEMBL_ACT_18789034
ROCK2	7.4	Ki	40	nM	CHEMBL_ACT_27181298
ROCK2	7.4	Ki	40	nM	CHEMBL_ACT_27389687
ROCK2	7.4	Ki	40	nM	CHEMBL_ACT_28004606
ROCK2	7.4	Ki	40	nM	CHEMBL_ACT_28678871
ROCK2	7.22	IC50	60	nM	CHEMBL_ACT_24861820
ROCK2	7.22	IC50	60	nM	CHEMBL_ACT_25086914
ROCK2	7.19	Kd	65	nM	CHEMBL_ACT_26618879
ROCK2	7	IC50	100	nM	CHEMBL_ACT_18789033
CSNK2A1	7	Ki	100	nM	CHEMBL_ACT_9586346
ROCK2	7	Ki	100	nM	CHEMBL_ACT_9627489
ROCK2	6.98	Ki	105	nM	CHEMBL_ACT_22401857
ROCK2	6.98	IC50	105	nM	CHEMBL_ACT_24872442
ROCK2	6.98	IC50	105	nM	CHEMBL_ACT_24987380
ROCK2	6.98	IC50	105	nM	CHEMBL_ACT_25695195
ROCK2	6.98	IC50	105	nM	CHEMBL_ACT_29156707
ROCK2	6.96	IC50	110	nM	CHEMBL_ACT_25728885
ROCK2	6.92	IC50	119.5	nM	CHEMBL_ACT_25728866
ROCK1	6.3	Ki	500	nM	CHEMBL_ACT_27181295
ROCK1	6.3	Ki	500	nM	CHEMBL_ACT_27389684
ROCK1	6.3	Ki	500	nM	CHEMBL_ACT_28004603
ROCK1	6.3	Ki	500	nM	CHEMBL_ACT_28678868
ROCK1	6.3	Ki	501.2	nM	CHEMBL_ACT_9652488
BLK	6	Ki	1000	nM	CHEMBL_ACT_9602424
ROCK2	5.99	IC50	1020	nM	CHEMBL_ACT_27181292
ROCK2	5.99	IC50	1020	nM	CHEMBL_ACT_27389681
ROCK2	5.99	IC50	1020	nM	CHEMBL_ACT_28004600
ROCK2	5.99	IC50	1020	nM	CHEMBL_ACT_28678865
DYRK1A	5.6	Ki	2512	nM	CHEMBL_ACT_9552569

Target pathways

Aggregated over 2 target gene(s): ROCK1, ROCK2.

Top Reactome pathways

40 total, by targets touching each:

Pathway	Targets	Genes
Developmental Biology	2	ROCK1, ROCK2
Signal Transduction	2	ROCK1, ROCK2
Disease	2	ROCK1, ROCK2
Signaling by VEGF	2	ROCK1, ROCK2
Signaling by Rho GTPases	2	ROCK1, ROCK2
RHO GTPase Effectors	2	ROCK1, ROCK2
EPH-Ephrin signaling	2	ROCK1, ROCK2
Signaling by GPCR	2	ROCK1, ROCK2
Semaphorin interactions	2	ROCK1, ROCK2
GPCR downstream signalling	2	ROCK1, ROCK2
EPHB-mediated forward signaling	2	ROCK1, ROCK2
EPHA-mediated growth cone collapse	2	ROCK1, ROCK2
Sema4D in semaphorin signaling	2	ROCK1, ROCK2
G alpha (12/13) signalling events	2	ROCK1, ROCK2
Sema4D induced cell migration and growth-cone collapse	2	ROCK1, ROCK2
Axon guidance	2	ROCK1, ROCK2
VEGFA-VEGFR2 Pathway	2	ROCK1, ROCK2
RHO GTPases Activate ROCKs	2	ROCK1, ROCK2
Infectious disease	2	ROCK1, ROCK2
RHOA GTPase cycle	2	ROCK1, ROCK2
Signaling by Receptor Tyrosine Kinases	2	ROCK1, ROCK2
RHO GTPase cycle	2	ROCK1, ROCK2
RHOB GTPase cycle	2	ROCK1, ROCK2
RHOC GTPase cycle	2	ROCK1, ROCK2
RHOH GTPase cycle	2	ROCK1, ROCK2
RHOBTB1 GTPase cycle	2	ROCK1, ROCK2
Nervous system development	2	ROCK1, ROCK2
Potential therapeutics for SARS	2	ROCK1, ROCK2
SARS-CoV Infections	2	ROCK1, ROCK2
RHOBTB GTPase Cycle	2	ROCK1, ROCK2

Dominant GO biological processes

GO term	Targets
mitotic cytokinesis	2
epithelial to mesenchymal transition	2
aortic valve morphogenesis	2
smooth muscle contraction	2
signal transduction	2
Rho protein signal transduction	2
positive regulation of cardiac muscle hypertrophy	2
positive regulation of gene expression	2
negative regulation of angiogenesis	2
actin cytoskeleton organization	2
regulation of cell adhesion	2
cortical actin cytoskeleton organization	2
actomyosin structure organization	2
regulation of actin cytoskeleton organization	2
positive regulation of MAPK cascade	2

Indications & clinical

Indications

10 indications (1 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
immune system disorder	4	MONDO:0005046	EFO:0000540
diffuse scleroderma	2	MONDO:0005019	EFO:0000404
psoriasis	2	MONDO:0005083	EFO:0000676
idiopathic pulmonary fibrosis	2	MONDO:0800504	EFO:0000768
graft versus host disease	2	MONDO:0013730	MONDO:0013730
liver disorder	1	MONDO:0005154	EFO:0001421
autoimmune disease	1	MONDO:0007179	EFO:0005809
plasma cell myeloma	1	MONDO:0009693	EFO:0001378

2 further indication records had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 31.

Phase distribution

Phase	Trials
PHASE2	15
PHASE1	9
PHASE4	2
PHASE3	2
PHASE1/PHASE2	2
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT07135973	PHASE4	NOT_YET_RECRUITING	A Study to Investigate Safety of Belumosudil in Participants Aged 12 Years and Above, With Chronic Graft-versus-host Disease (cGVHD)
NCT06616415	PHASE4	COMPLETED	A Clinical Study to Evaluate the Pharmacokinetics, Efficacy, and Safety of Belumosudil in Chinese Adolescents With cGVHD Who Have Had an Inadequate Response to Glucocorticoids or Other Systemic Therapies
NCT06082037	PHASE3	RECRUITING	A Study to Test How Effective Belumosudil Tablets Are for Treating Adult Participants With Chronic Lung Allograft Dysfunction
NCT06143891	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Test an Oral Medicine, Belumosudil, in Combination With Corticosteroids in Participants at Least 12 Years of Age With Newly Diagnosed Chronic Graft Versus Host Disease.
NCT04643002	PHASE1/PHASE2	RECRUITING	Isatuximab in Combination With Novel Agents in RRMM - Master Protocol
NCT05922761	PHASE2	RECRUITING	BElumosudil for Bronchiolitis Obliterans Prevention/Therapy (BEBOP)
NCT05996627	PHASE2	RECRUITING	Belumosudil for the Pre-emptive Treatment of Patients With Chronic Graft Versus Host Disease
NCT06046248	PHASE2	RECRUITING	Belumosudil and Rituximab for Primary Treatment of Chronic Graft-Versus-Host-Disease
NCT06105554	PHASE1/PHASE2	RECRUITING	Phase I/II Open Label Study of Belumosudil Mesylate Alone, and in Combination With Dexamethasone, in Patients With Relapsed/Refractory Multiple Myeloma
NCT06476132	PHASE2	RECRUITING	Belumosudil to Block Chronic Lung Allograft Dysfunction (CLAD) in High Risk Lung Transplant Recipients
NCT07006506	PHASE2	RECRUITING	A Study of Belumosudil in People at Risk of Developing Graft-Versus-Host Disease After a Stem Cell Transplant
NCT07116031	PHASE2	RECRUITING	A Study of Belumosudil in Children With Chronic Graft Versus Host Disease (schoolROCK)
NCT02106195	PHASE2	COMPLETED	A Safety and Tolerability Study of Belumosudil (KD025) Treatment in Subjects With Moderately Severe Psoriasis Vulgaris
NCT02317627	PHASE2	COMPLETED	Phase 2, Open-label, Study of KD025 in Subjects With Psoriasis Vulgaris Who Failed First-line Therapy
NCT02688647	PHASE2	COMPLETED	A 2-Part, Phase 2 Open-label and Crossover Study of Belumosudil for Treatment of Idiopathic Pulmonary Fibrosis
NCT02841995	PHASE2	COMPLETED	A Study to Evaluate the Safety, Tolerability, and Activity of KD025 in Subjects With Chronic Graft Versus Host Disease
NCT02852967	PHASE2	COMPLETED	A Phase 2, Double-blind, Placebo-controlled Study of the Efficacy and Safety of Belumosudil in Subjects With Moderate/Severe Chronic Plaque Psoriasis
NCT03640481	PHASE2	TERMINATED	Efficacy and Safety of KD025 in Subjects With cGVHD After At Least 2 Prior Lines of Systemic Therapy
NCT03919799	PHASE2	TERMINATED	KD025 in Subjects With Diffuse Cutaneous Systemic Sclerosis
NCT04680975	PHASE2	TERMINATED	Efficacy and Safety of Belumosudil in Subjects With Diffuse Cutaneous Systemic Sclerosis
NCT05567406	PHASE2	WITHDRAWN	Safety and Efficacy of Oral Belumosudil in Black or African American, American Indian or Alaska Native, and Native Hawaiian or Other Pacific Islander Male and Female Participants Aged 12 Years and Above With Chronic Graft Versus Host Disease (cGVHD) After At Least 2 Prior Lines of Systemic Therapy
NCT05806749	PHASE1	ACTIVE_NOT_RECRUITING	Immunological Tolerance in Patients With Mismatched Kidney Transplants
NCT07484113	PHASE1	NOT_YET_RECRUITING	IL6-receptor Inhibitor Iwith Belumosudil for the Treatment of Belumosudil-refractory cGVHD
NCT02557139	PHASE1	COMPLETED	Bioavailability of Belumosudil (KD025) in Healthy Male Subjects
NCT03530995	PHASE1	COMPLETED	Drug-drug Interaction Between Belumosudil, Itraconazole, Rifampicin, Rabeprazole, and Omeprazole in Healthy Volunteers
NCT04166942	PHASE1	COMPLETED	KD025 Hepatic Impairment Study With Normal Hepatic Function and Subjects With Varying Degrees of Hepatic Impairment
NCT05806567	PHASE1	COMPLETED	A Study to Assess the Effect of Oral Belumosudil on Inhibition of Various Proteins in the Fed State in Healthy Male Subjects
NCT05918588	PHASE1	COMPLETED	A Study to Determine the Effect of Multiple Oral Doses and Regimens of KD025 in Healthy Male and Post-menopausal Female Subjects
NCT05918614	PHASE1	COMPLETED	A Study to Determine the Effect of 500 mg Oral Dose of KD025 in Healthy Male and Post-menopausal Female Subjects
NCT05918627	PHASE1	COMPLETED	A Study to Determine the Effect of Multiple Oral Doses of SLx-2119 in Healthy Male Subjects
NCT05382377	EARLY_PHASE1	UNKNOWN	NKG2D CAR-T(KD-025) in the Treatment of Advanced NKG2DL+ Solid Tumors

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline or drug-level clinical/variant annotations in PharmGKB for this molecule.

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

51 molecules share ≥1 primary target. Top 51 by shared-target count:

Molecule	Source	Status	Shared targets
CRIZOTINIB	ChEMBL + PubChem	Phase 4 (approved)	ROCK1, ROCK2
BARICITINIB	ChEMBL	Phase 4 (approved)	ROCK1, ROCK2
BOSUTINIB	ChEMBL	Phase 4 (approved)	ROCK1, ROCK2
CAPIVASERTIB	ChEMBL	Phase 4 (approved)	ROCK1, ROCK2
FEDRATINIB	ChEMBL	Phase 4 (approved)	ROCK1, ROCK2
MIDOSTAURIN	ChEMBL	Phase 4 (approved)	ROCK1, ROCK2
MOMELOTINIB	ChEMBL	Phase 4 (approved)	ROCK1, ROCK2
NETARSUDIL	ChEMBL	Phase 4 (approved)	ROCK1, ROCK2
RUXOLITINIB	ChEMBL	Phase 4 (approved)	ROCK1, ROCK2
SUNITINIB	ChEMBL	Phase 4 (approved)	ROCK1, ROCK2
TOFACITINIB	ChEMBL	Phase 4 (approved)	ROCK1, ROCK2
UPADACITINIB	ChEMBL	Phase 4 (approved)	ROCK1, ROCK2
AFURESERTIB	ChEMBL	Phase 3	ROCK1, ROCK2
ALVOCIDIB	ChEMBL	Phase 3	ROCK1, ROCK2
DOVITINIB	ChEMBL	Phase 3	ROCK1, ROCK2
FASUDIL	ChEMBL	Phase 3	ROCK1, ROCK2
LESTAURTINIB	ChEMBL	Phase 3	ROCK1, ROCK2
LINIFANIB	ChEMBL	Phase 3	ROCK1, ROCK2
RIPASUDIL	ChEMBL	Phase 3	ROCK1, ROCK2
CENISERTIB	ChEMBL	Phase 2	ROCK1, ROCK2
DECERNOTINIB	ChEMBL	Phase 2	ROCK1, ROCK2
ILORASERTIB	ChEMBL	Phase 2	ROCK1, ROCK2
LAUROGUADINE	ChEMBL	Phase 2	ROCK1, ROCK2
R-406	ChEMBL	Phase 2	ROCK1, ROCK2
RG-547	ChEMBL	Phase 2	ROCK1, ROCK2
RIPASUDIL HYDROCHLORIDE DIHYDRATE	ChEMBL	Phase 2	ROCK1, ROCK2
SAR-407899 FREE BASE	ChEMBL	Phase 2	ROCK1, ROCK2
SU-014813	ChEMBL	Phase 2	ROCK1, ROCK2
UCN-01	ChEMBL	Phase 2	ROCK1, ROCK2
UPROSERTIB	ChEMBL	Phase 2	ROCK1, ROCK2
VEROSUDIL	ChEMBL	Phase 2	ROCK1, ROCK2
ZOTIRACICLIB	ChEMBL	Phase 2	ROCK1, ROCK2
Afatinib	PubChem	Approved	ROCK1, ROCK2
Binimetinib	PubChem	Approved	ROCK1, ROCK2
dacomitinib	PubChem	Approved	ROCK1, ROCK2
Fostamatinib	PubChem	Approved	ROCK1, ROCK2
Gefitinib	PubChem	Approved	ROCK1, ROCK2
Idelalisib	PubChem	Approved	ROCK1, ROCK2
Pazopanib	PubChem	Approved	ROCK1, ROCK2
regorafenib	PubChem	Approved	ROCK1, ROCK2
Selumetinib	PubChem	Approved	ROCK1, ROCK2
Trametinib	PubChem	Approved	ROCK1, ROCK2
CERITINIB	ChEMBL	Phase 4 (approved)	ROCK2
PALBOCICLIB	ChEMBL	Phase 4 (approved)	ROCK2
VANDETANIB	ChEMBL	Phase 4 (approved)	ROCK2
BMS-690514	ChEMBL	Phase 2	ROCK1
FORETINIB	ChEMBL	Phase 2	ROCK2
PH-797804	ChEMBL	Phase 2	ROCK2
SIMUROSERTIB	ChEMBL	Phase 2	ROCK1
VX-702	ChEMBL	Phase 2	ROCK1
Belzutifan	PubChem	Approved	ROCK2