Details
| Stereochemistry | ACHIRAL |
| Molecular Formula | C26H24N6O2.C3H3F3O2 |
| Molecular Weight | 580.5577 |
| Optical Activity | NONE |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
OC(=O)CC(F)(F)F.CC(C)NC(=O)COC1=CC=CC(=C1)C2=NC3=C(C=CC=C3)C(NC4=CC=C5NN=CC5=C4)=N2
InChI
InChIKey=PBWWPJDQYJXRII-UHFFFAOYSA-N
InChI=1S/C26H24N6O2.C3H3F3O2/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;4-3(5,6)1-2(7)8/h3-14,16H,15H2,1-2H3,(H,27,32)(H,28,33)(H,29,30,31);1H2,(H,7,8)
DescriptionCurator'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
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.
Originator
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
Target ID: CHEMBL2973 |
60.0 nM [IC50] | ||
Target ID: CHEMBL3390822 |
|||
Target ID: Q9HBE4 Gene ID: 59067.0 Gene Symbol: IL21 Target Organism: Homo sapiens (Human) |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Primary | Unknown Approved UseUnknown |
|||
| Primary | Unknown Approved UseUnknown |
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
128.4 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32192179 |
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
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
48.7 μg × min/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32192179 |
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
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
353.4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32192179 |
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
| Dose | Population | Adverse 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%) Sources: Page: p.3811AST increased (33.3%) |
AEs
| AE | Significance | Dose | Population |
|---|---|---|---|
| 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 |
PubMed
| Title | Date | PubMed |
|---|---|---|
| Selective oral ROCK2 inhibitor down-regulates IL-21 and IL-17 secretion in human T cells via STAT3-dependent mechanism. | 2014 Nov 25 |
|
| Targeted Rho-associated kinase 2 inhibition suppresses murine and human chronic GVHD through a Stat3-dependent mechanism. | 2016 Apr 28 |
|
| ROCK2 signaling is required to induce a subset of T follicular helper cells through opposing effects on STATs in autoimmune settings. | 2016 Jul 19 |
Patents
Sample Use Guides
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|---|---|---|---|---|
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Common Name | English | ||
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Systematic Name | English |
| Code System | Code | Type | Description | ||
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LL4OG4RZ5D
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911417-96-4
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NON-SPECIFIC STOICHIOMETRY | |||
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1243152-02-4
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154572893
Created by
admin on Sat Dec 16 15:55:31 GMT 2023 , Edited by admin on Sat Dec 16 15:55:31 GMT 2023
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ACTIVE MOIETY
SUBSTANCE RECORD
