P-[[[(1R,2S)-2-AMINOCYCLOHEXYL]AMINO]CARBONYL]-PHOSPHONIC ACID

Matrix metalloproteinases (MMPs) belong to a family of proteases that play a crucial role in tissue remodeling and repair by degrading extracellular matrix proteins, thus enabling cell migration. Overexpression of MMPs are linked to diseases such as cancer, arthritis, osteoporosis, and arteriosclerosis. cis-ACCP is a reversible and competitive inhibitor of type IV collagen-specific MMP-2 and MMP-9 with preference towards MMP-2 (IC₅₀ = 4 and 20 μM, respectively). At 100 μM, cis-ACCP prevents 90% of tumor cell invasion across matrigel-coated membranes in vitro.

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

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].

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].

4 and 20 μm for mmp-2 and mmp-9, respectively

[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).