belumosudil 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | BioActivity |

Stem definitionDrug idCAS RN
Rho protein kinase inhibitors 5467 911417-87-3

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • belumosudil
  • belumosudil mesylate
  • rezurock
  • KD025
  • SLx-2119
Belumosudil is an inhibitor of rho-associated, coiled-coil containing protein kinase (ROCK) which inhibits ROCK2 and ROCK1 with IC50 values of approximately 100 nanoM and 3 microM, respectively. Belumosudil downregulated proinflammatory responses via regulation of STAT3/STAT5 phosphorylation and shifting Th17/Treg balance in ex-vivo or in vitro-human T cell assays. Belumosudil also inhibited aberrant pro-fibrotic signaling, in vitro. In vivo, belumosudil demonstrated activity in animal models of chronic GVHD.
  • Molecular weight: 452.52
  • Formula: C26H24N6O2
  • CLOGP: 5.02
  • LIPINSKI: 0
  • HAC: 8
  • HDO: 3
  • TPSA: 104.82
  • ALOGS: -5.19
  • ROTB: 7
  • Status: ONP
    • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

None

ADMET properties:

None

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 4.281 High 1
caco2-efflux Caco-2 efflux ratio (BA/AB) 11.588 High 1
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 28.379 10^-6 cm/s High 1
dh-clint Dog hepatocyte intrinsic clearance 20.091 uL/min/10^6 cells High 1
dppb Dog plasma protein binding (% unbound) 0.490 % High 1
fcs-ppb Fetal calf serum protein binding (% unbound) 2.040 % High 1
herg hERG pIC50 5.364 pIC50 High 1
hh-clint Human hepatocyte intrinsic clearance 17.498 uL/min/10^6 cells High 1
hlm-clint Human liver microsomal intrinsic clearance 43.954 uL/min/mg protein High 1
hppb Human plasma protein binding (% unbound) 0.480 % High 1
kinase-safety-class ACVR2A,ACVR2B,AKT2,AKT3,ALK,AURKA,AURKB,AURKC,AXL,BRAF,BTK,CAMK2B,CAMK2D,CDK1,CDK5,CDK9,CHEK1,CLK4,CSF1R,DDR1,DYRK1A,DYRK1B,EGFR,EIF2AK3,EPHB4,ERBB2,FLT3,GRK1,GRK2,GRK3,GSK3B,IKBKB,INSR,IRAK1,IRAK3,ITK,JAK1,JAK2,JAK3,KDR,KIT,MAP2K6,MAP3K1,MAP3K10,MAP3K11,MAP3K21,MAP3K7,MAP4K1,MAP4K2,MAP4K3,MAP4K5,MAPK1,MAPK10,MAPK7,MAPK9,MAPKAPK2,MARK4,MELK,MET,MTOR,NTRK1,NTRK2,PDK1,PDK2,PDK4,PDPK1,PIK3CA,PIK3CB,PIK3CD,PIK3CG,PIM2,PRKCD,PRKDC,ROCK1,SGK1,SIK2,SIK3,STK33,SYK,TEK,TNIK,TTK,ULK1,ULK2 84
kinase-selectivity-class ACVR2A,ACVR2B,AURKA,AURKB,BRAF,CAMK2D,DYRK1B,EGFR,MAP2K3,MAP2K6,MAP3K10,MAP3K21,MAPK7,PDK1,PDK4,SGK1,SIK2,SIK3,STK33,TTK 20
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 36.813 High 1
mh-clint Mouse hepatocyte intrinsic clearance 46.238 High 1
mppb Mouse plasma protein binding (% unbound) 0.470 High 1
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 34.754 High 1
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pppb Pig plasma protein binding (% unbound) 1.910 % High 1
rh-clint Rat hepatocyte intrinsic clearance 59.979 uL/min/10^6 cells High 1
rh-fuinc Rat hepatocyte fraction unbound in incubation 3.850 % High 1
rppb Rat plasma protein binding (% unbound) 0.600 % High 1
solubility-dd Solubility at pH 7.4 in DMSO 0.828 uM High 1

Approvals:

DateAgencyCompanyOrphan
July 16, 2021 FDA KADMON PHARMA LLC

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Inappropriate schedule of product administration 313.22 30.10 119 1895 149814 90476619
Product use in unapproved indication 241.01 30.10 126 1888 336110 90290323
Hospitalisation 55.93 30.10 35 1979 128065 90498368
Bronchopulmonary aspergillosis 38.49 30.10 13 2001 11385 90615048
Phaeohyphomycosis 31.98 30.10 6 2008 477 90625956
Fatigue 31.75 30.10 75 1939 1153948 89472485

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Inappropriate schedule of product administration 495.80 37.56 180 1827 95722 42523606
Product use in unapproved indication 381.88 37.56 180 1827 184276 42435052
Hospitalisation 79.05 37.56 47 1960 74283 42545045
Alveolar proteinosis 70.22 37.56 14 1993 716 42618612

FDA Adverse Event Reporting System (Geriatric)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Inappropriate schedule of product administration 785.91 26.84 297 4171 203340 110381491
Product use in unapproved indication 587.29 26.84 306 4162 447071 110137760
Hospitalisation 139.56 26.84 81 4387 142412 110442419
Alveolar proteinosis 72.93 26.84 16 4452 1520 110583311
Chronic graft versus host disease 55.65 26.84 19 4449 9438 110575393
Dry eye 47.42 26.84 29 4439 55764 110529067
Fatigue 45.39 26.84 129 4339 1215829 109369002
Chronic graft versus host disease oral 40.02 26.84 8 4460 483 110584348
Pneumonia 37.60 26.84 98 4370 876616 109708215
COVID-19 36.26 26.84 47 4421 245013 110339818
Emotional disorder 35.86 26.84 16 4452 16144 110568687
Product dose omission in error 33.02 26.84 17 4451 23495 110561336
Influenza 32.44 26.84 37 4431 169064 110415767
Graft versus host disease in lung 32.40 26.84 8 4460 1270 110583561
Death 31.85 26.84 80 4388 698789 109886042
Graft versus host disease in skin 31.35 26.84 12 4456 8242 110576589
Chronic graft versus host disease in skin 31.11 26.84 9 4459 2610 110582221
Depressed mood 30.95 26.84 23 4445 60786 110524045
Graft versus host disease 30.52 26.84 15 4453 18791 110566040
Chronic graft versus host disease in eye 29.16 26.84 6 4462 419 110584412
Cough 27.78 26.84 59 4409 461582 110123249

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC L04AA48 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
IMMUNOSUPPRESSANTS
IMMUNOSUPPRESSANTS
Selective immunosuppressants
MeSH PA D004791 Enzyme Inhibitors
MeSH PA D047428 Protein Kinase Inhibitors
CHEBI has role CHEBI:35610 antineoplastic agent
CHEBI has role CHEBI:50748 antipsoriatic
CHEBI has role CHEBI:233423 antifibrotic agent

Related Drugs by ATC class:

L04AA Selective immunosuppressants 10 drugs
abataceptalefaceptapremilastbelataceptcladribinegusperimusimlifidasemycophenolic acidnerandomilastremibrutinib

Drug Use | Suggest Off label Use Form| |View source of the data|

DiseaseRelationSNOMED_IDDOID
Chronic graft-versus-host disease (chronic GVHD) indication 402356004




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

None

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
EQ 200MG BASE REZUROCK KADMON PHARMS LLC N214783 July 16, 2021 RX TABLET ORAL 10183931 Oct. 7, 2033 FOR THE TREATMENT OF CHRONIC GRAFT VERSUS HOST DISEASE
EQ 200MG BASE REZUROCK KADMON PHARMS LLC N214783 July 16, 2021 RX TABLET ORAL 10183931 Oct. 7, 2033 TREATMENT OF CHRONIC GRAFT-VERSUS-HOST DISEASE (CHRONIC GVHD) AFTER FAILURE OF AT LEAST TWO PRIOR LINES OF SYSTEMIC THERAPY IN ADULT AND PEDIATRIC PATIENTS 12 YEARS AND OLDER
EQ 200MG BASE REZUROCK KADMON PHARMS LLC N214783 July 16, 2021 RX TABLET ORAL 10696660 Oct. 7, 2033 FOR THE TREATMENT OF CHRONIC GRAFT VERSUS HOST DISEASE
EQ 200MG BASE REZUROCK KADMON PHARMS LLC N214783 July 16, 2021 RX TABLET ORAL 10696660 Oct. 7, 2033 TREATMENT OF CHRONIC GRAFT-VERSUS-HOST DISEASE (CHRONIC GVHD) AFTER FAILURE OF AT LEAST TWO PRIOR LINES OF SYSTEMIC THERAPY IN ADULT AND PEDIATRIC PATIENTS 12 YEARS AND OLDER
EQ 200MG BASE REZUROCK KADMON PHARMS LLC N214783 July 16, 2021 RX TABLET ORAL 8357693 June 20, 2034 TREATMENT OF CHRONIC GRAFT-VERSUS-HOST DISEASE (CHRONIC GVHD) AFTER FAILURE OF AT LEAST TWO PRIOR LINES OF SYSTEMIC THERAPY IN ADULT AND PEDIATRIC PATIENTS 12 YEARS AND OLDER THROUGH INHIBITING RHO-ASSOCIATED, COILED-COIL CONTAINING PROTEIN KINASE
EQ 200MG BASE REZUROCK KADMON PHARMS LLC N214783 July 16, 2021 RX TABLET ORAL 11311541 April 9, 2035 TREATMENT OF ADULTS AND PEDIATRIC PATIENTS 12 AND OLDER WITH SCLERODERMATOUS FORM OF CHRONIC GRAFT-VERSUS-HOST DISEASE ( CGVHD) AFTER FAILURE OF AT LEAST TWO PRIOR LINES OF SYSTEMIC THERAPY
EQ 200MG BASE REZUROCK KADMON PHARMS LLC N214783 July 16, 2021 RX TABLET ORAL 12097202 July 14, 2042 TREATMENT OF CHRONIC GRAFT-VERSUS-HOST DISEASE (CHRONIC GVHD) AFTER FAILURE OF AT LEAST TWO PRIOR LINES OF SYSTEMIC THERAPY IN ADULT AND PEDIATRIC PATIENTS 12 YEARS AND OLDER WITH A GRADE 3 INFECTION ADVERSE REACTION

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
EQ 200MG BASE REZUROCK KADMON PHARMS LLC N214783 July 16, 2021 RX TABLET ORAL July 16, 2026 NEW CHEMICAL ENTITY
EQ 200MG BASE REZUROCK KADMON PHARMS LLC N214783 July 16, 2021 RX TABLET ORAL July 16, 2028 TREATMENT OF ADULT AND PEDIATRIC PATIENTS 12 YEARS AND OLDER WITH CHRONIC GRAFT-VERSUS-HOST DISEASE (CHRONIC GVHD) AFTER FAILURE OF AT LEAST TWO PRIOR LINES OF SYSTEMIC THERAPY

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])		Mechanism
action		Bioact sourceMoA source
Rho-associated protein kinase 1 Kinase INHIBITOR IC50 5.52 DRUG LABEL DRUG LABEL
Rho-associated protein kinase 2 Kinase INHIBITOR IC50 5.52 DRUG LABEL DRUG LABEL

External reference:

IDSource
834YJF89WO UNII
2109704-99-4 SECONDARY_CAS_RN
C5418179 UMLSCUI
CHEBI:750359 CHEBI
ICQ PDB_CHEM_ID
CHEMBL2005186 ChEMBL_ID
D11815 KEGG_DRUG
11950170 PUBCHEM_CID
DB16703 DRUGBANK_ID
CHEMBL4802130 ChEMBL_ID
11343 INN_ID
C000718240 MESH_SUPPLEMENTAL_RECORD_UI
C000619755 MESH_SUPPLEMENTAL_RECORD_UI
9558 IUPHAR_LIGAND_ID
1163566003 SNOMEDCT_US
1163567007 SNOMEDCT_US
1163571005 SNOMEDCT_US
4040727 VANDF
348524 MMSL
39721 MMSL
d09774 MMSL
018817 NDDF
018818 NDDF
2564025 RXNORM
834YJF89WO INXIGHT DRUGS

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Rezurock HUMAN PRESCRIPTION DRUG LABEL 1 79802-200 TABLET 200 mg ORAL NDA 30 sections