| 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
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
| Molecular Formula | C22H36N4O5 |
| Molecular Weight | 436.545 |
| Charge | 0 |
| Count |
MOL RATIO
1 MOL RATIO (average) |
| Stereochemistry | ABSOLUTE |
| Additional Stereochemistry | No |
| Defined Stereocenters | 2 / 2 |
| E/Z Centers | 0 |
| Optical Activity | UNSPECIFIED |
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
Overview
| CYP3A4 | CYP2C9 | CYP2D6 | hERG |
|---|---|---|---|
OverviewOther
| Other Inhibitor | Other Substrate | Other Inducer |
|---|---|---|
Drug as victim
Sourcing
PubMed
Patents
Sample Use Guides
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.
