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 8297	2.3 nM [IC50]
Matrix metalloproteinase 8 6 Target ID: CHEMBL4588 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10669559	Inhibitor 8297	4.0 nM [Ki]
Matrix metalloproteinase 13 8 Target ID: CHEMBL280 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19422229	Inhibitor 8297	4.7 nM [IC50]
Matrix metalloproteinase 9 20 Target ID: CHEMBL321 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19422229	Inhibitor 8297	2.4 nM [IC50]
Matrix metalloproteinase 7 3 Target ID: CHEMBL4073 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19422229	Inhibitor 8297	18.5 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Rheumatoid arthritis 316 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11371662	Primary		Phase II 1132	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 270

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP 270	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/11371662/	yes

Sourcing

Vendor/Aggregator	ID	URL
Compound Cloud	9824350
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
eMolecules	31206071	https://orderbb.emolecules.com/search/#?query=31206071

PubMed

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

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 `Fri Dec 15 15:55:08 GMT 2023` Edited by `admin` on `Fri Dec 15 15:55:08 GMT 2023`
Record UNII	02HQ4TYQ60
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

CIPEMASTAT

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

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Code System Code Type Description

EPA CompTox

DTXSID10897569

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FDA UNII

02HQ4TYQ60

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USAN

LL-08

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PUBCHEM

9824350

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EVMPD

SUB16410MIG

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NCI_THESAURUS

C96297

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WIKIPEDIA

CIPEMASTAT

Created by admin on Fri Dec 15 15:55:09 GMT 2023 , Edited by admin on Fri Dec 15 15:55:09 GMT 2023

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ChEMBL

CHEMBL115653

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CAS

190648-49-8

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INN

7862

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SMS_ID

100000078557

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Related Record Type Details


					20Q1PNI82X

INTERSTITIAL COLLAGENASE

TARGET -> INHIBITOR

Related Record Type Details


					02HQ4TYQ60

CIPEMASTAT

ACTIVE MOIETY

Details

SMILES

InChI

DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/11371662Curator'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

Originator

Approval Year

Targets

Conditions

Approved Use

Approved Use

Cmax

AUC

T1/2

Overview

OverviewOther

Drug as victim

Sourcing

PubMed

Patents

Sample Use Guides

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

C_max

T_1/2