CIPEMASTAT

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 Search

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

Molecular Formula	C22H36N4O5
Molecular Weight	436.545
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	2 / 2
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/11371662
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.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Matrix metalloproteinase-1 8 Target ID: CHEMBL332 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19422229	Inhibitor 8504	2.3 nM [IC50]
Matrix metalloproteinase 8 6 Target ID: CHEMBL4588 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10669559	Inhibitor 8504	4.0 nM [Ki]
Matrix metalloproteinase 13 8 Target ID: CHEMBL280 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19422229	Inhibitor 8504	4.7 nM [IC50]
Matrix metalloproteinase 9 20 Target ID: CHEMBL321 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19422229	Inhibitor 8504	2.4 nM [IC50]
Matrix metalloproteinase 7 3 Target ID: CHEMBL4073 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19422229	Inhibitor 8504	18.5 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Rheumatoid arthritis 320 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11371662	Primary		Phase II 1147	Unknown Approved Use Unknown
Osteoarthritis 157 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9751097	Primary		Basic research	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
3323 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11371662	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11371662	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

Value	Dose	Co-administered	Analyte	Population
19.71 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11371662	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11371662	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

T_1/2

Value	Dose	Co-administered	Analyte	Population
23.9 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11371662	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

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP 303

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP 303	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/11371662/	yes

Sourcing

Vendor/Aggregator	ID	URL
Compound Cloud	9824350
eMolecules	31206071	https://orderbb.emolecules.com/search/#?query=31206071
MuseChem	I010648	https://www.musechem.com/product/I010648.html
Tocris	2916	https://www.tocris.com/search.php?Type=QuickSearch&Value=2916
Toronto Research Chemicals	R700905	https://www.trc-canada.com/product-detail/?CatNum=R700905
Toronto Research Chemicals	S550073	https://www.trc-canada.com/product-detail/?CatNum=S550073
Wonderchem	WD05HUN	http://www.wonder-chem.com/search.html?text=WD05HUN

PubMed

Title	Date	PubMed
The new synthetic matrix metalloproteinase inhibitor (Roche 28-2653) reduces tumor growth and prolongs survival in a prostate cancer standard rat model.	2002-03-27	11960381
Matrix metalloproteinase inhibitors in rheumatic diseases.	2001-11	11890658
Tolerability and pharmacokinetics of the collagenase-selective inhibitor Trocade in patients with rheumatoid arthritis.	2001-05	11371662

Patents

Sample Use Guides

In Vivo Use Guide

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.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 18:13:10 GMT 2025` Edited by `admin` on `Mon Mar 31 18:13:10 GMT 2025`
Record UNII	02HQ4TYQ60
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

CIPEMASTAT

Official Name

English

TROCADE

Preferred 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

(?R,?R)-?-(Cyclopentylmethyl)-?-oxo-?-[(3,4,4-piperidinebutyrohydroxamic acid

Common Name

English

cipemastat [INN]

Common 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