cis-ACCP IV型胶原特异性MMP-2和MMP-9YZ剂

IC50: 4 and 20 μM for MMP-2 and MMP-9, respectively

cis-ACCP is a type IV collagen-specific MMP-2 and MMP-9 inhibitor.

Matrix metalloproteinases (MMPs) belong to a family of proteases that play a keyrole in tissue remodeling and repair via degrading extracellular matrix proteins, therefore enabling cell migration.

In vitro: cis-ACCP could preferentially inhibit MMP-2 and MMP-9 with a preference for MMP-2. The trans-ACCP did not inhibit the gelatinases but had moderate activity against MMP-3 and MMP-13. These findings indicated specificity of the compounds regarding binding to the enzymes. Furthermore, addition of cis-ACCP to tumor cells was able to prevent their traversion dose-dependently, about 90% at the highest concentration tested [1].

In vivo: Aninmal study showd that cis-ACCP could reduce metastasis formation in mice by approximately 90% when administered by a repetitive once daily dosing regimen at 50 mg/kg via oral or i.p. routes and was nontoxic up to 500 mg/kg, following i.p. administration daily for two weeks. In addition, the pharmacokinetic investigation in rats revealed distribution restricted into the extracellular fluid, the site of action for the antimetastatic activity and rapid elimination from blood [1].

Clinical trial: So far, no clinical study has been conducted.

cis-ACCP  IV型胶原特异性MMP-2和MMP-9YZ剂Reference:
[1] Hoffman, A. ,Qadri, B.,Frant, J., et al. Carbamoylphosphonate matrix metalloproteinase inhibitors 6: Cis-2-aminocyclohexylcarbamoylphosphonic acid, a novel orally active antimetastatic matrix metalloproteinase-2 selective inhibitor-synthesis and pharmacodynamic and pharmacokinetic analysis. Journal of Medicinal Chemistry 51, 1406-1414 (2008).