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Details

Stereochemistry ABSOLUTE
Molecular Formula C22H36N4O5
Molecular Weight 436.545
Optical Activity UNSPECIFIED
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of CIPEMASTAT

SMILES

CN1C(=O)N(C[C@@H]([C@@H](CC2CCCC2)C(=O)N3CCCCC3)C(=O)NO)C(=O)C1(C)C

InChI

InChIKey=GFUITADOEPNRML-SJORKVTESA-N
InChI=1S/C22H36N4O5/c1-22(2)20(29)26(21(30)24(22)3)14-17(18(27)23-31)16(13-15-9-5-6-10-15)19(28)25-11-7-4-8-12-25/h15-17,31H,4-14H2,1-3H3,(H,23,27)/t16-,17+/m1/s1

HIDE SMILES / InChI

Description
Curator's Comment: the description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/9179398 | https://www.ncbi.nlm.nih.gov/pubmed/24491581

Cipemastat (Ro 32-3555, tentative trade name Trocade) is a dipeptide, potent, competitive inhibitor of matrix metalloproteinases (MMP) 1, 8 and 13, which was under development by Roche for the potential treatment of rheumatoid arthritis. Cipemastat is a selective inhibitor of metalloproteinases 1, 8 and 13 over the related human matrix metalloproteinases stromelysin 1, and gelatinases A and B. Cipemastat mediated MMP inhibition leads to block the final common event in the destructive cascade resulting in the breakdown of cartilage and bone. Trocade has also been shown to inhibit cartilage destruction in vivo and to prevent structural joint damage in animal models of rheumatoid and osteoarthritis. Cipemastat was in phase II clinical trials for the treatment of rheumatoid arthritis. However, Roche discontinued the development of cipemastat because of an unfavorable risk-benefit profile.

Approval Year

Targets

Targets

Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
3323 ng/mL
150 mg 1 times / day multiple, oral
dose: 150 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
CIPEMASTAT plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
3566 ng/mL
150 mg single, oral
dose: 150 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
CIPEMASTAT plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
19.71 mg × h/L
150 mg 1 times / day multiple, oral
dose: 150 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
CIPEMASTAT plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
20.66 mg × h/L
150 mg single, oral
dose: 150 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
CIPEMASTAT plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
23.9 h
150 mg 1 times / day multiple, oral
dose: 150 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
CIPEMASTAT plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer

Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
yes
PubMed

PubMed

TitleDatePubMed
Matrix metalloproteinase inhibitors in rheumatic diseases.
2001 Nov
Patents

Patents

Sample Use Guides

25, 50, 100 or 150 mg once daily for 28 days.
Route of Administration: Oral
In Vitro Use Guide
Bovine nasal cartilage explants (25 ± 30 mg) were cultured at 37C in Dulbecco's modified Eagle's medium (DMEM) containing penicillin (50 mkg/ml, streptomycin (50 mg/ml) and fungizone (250 mg/ml). Degradation of collagen was induced by the addition of114 ng/ml of rHu-IL-1alpha to the culture medium, the cultures were incubated for 15 days. During this period culture media containing rHu-IL-1alpha and Cipemastat were renewed every 7 days. When a considerable portion of each cartilage piece had degraded, the assay was stopped by removing the remaining cartilage explant and then analyzed for hydroxyproline, as a marker of cartilage collagen content. Glucose utilization was determined by measuring the glucose concentration in culture medium around the explants at the end of the experiment. The samples were analyzed by a COBAS Bio (Roche Diagnostics) with a GlucHK-unimate 5 test kit. Ro 32-3555 inhibited interleukin-1a (IL-1a)-induced cartilage collagen degradation in vitro in bovine nasal cartilage explants with IC50=60 nM.
Name Type Language
CIPEMASTAT
INN   USAN   WHO-DD  
INN   USAN  
Official Name English
RO-32-3555/000
Code English
Cipemastat [WHO-DD]
Common Name English
1-PIPERIDINEBUTANAMIDE, .BETA.-(CYCLOPENTYLMETHYL)-N-HYDROXY-.GAMMA.-OXO-.ALPHA.-((3,4,4-TRIMETHYL-2,5-DIOXO-1-IMIDAZOLIDINYL)METHYL)-, (R-(R*,R*))-
Common Name English
RO-32-03555
Code English
(αR,βR)-β-(Cyclopentylmethyl)-γ-oxo-α-[(3,4,4-piperidinebutyrohydroxamic acid
Common Name English
cipemastat [INN]
Common Name English
TROCADE
Brand Name English
CIPEMASTAT [USAN]
Common Name English
RO-323555000
Code English
RO 32-3555/000
Code English
Classification Tree Code System Code
NCI_THESAURUS C1970
Created by admin on Fri Dec 15 15:55:08 GMT 2023 , Edited by admin on Fri Dec 15 15:55:08 GMT 2023
Code System Code Type Description
EPA CompTox
DTXSID10897569
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PRIMARY
FDA UNII
02HQ4TYQ60
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PRIMARY
USAN
LL-08
Created by admin on Fri Dec 15 15:55:08 GMT 2023 , Edited by admin on Fri Dec 15 15:55:08 GMT 2023
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PUBCHEM
9824350
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EVMPD
SUB16410MIG
Created by admin on Fri Dec 15 15:55:08 GMT 2023 , Edited by admin on Fri Dec 15 15:55:08 GMT 2023
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NCI_THESAURUS
C96297
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WIKIPEDIA
CIPEMASTAT
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ChEMBL
CHEMBL115653
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CAS
190648-49-8
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INN
7862
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PRIMARY
SMS_ID
100000078557
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PRIMARY