(R)-3-((S)-1-((S)-2-methoxy-1-phenylethylamino)-3,3-dimethyl-1-oxobutan-2-ylcarbamoyl)-6-(2-methylbiphenyl-4-yl)hexanoic acid

The potency of UK-370106 (compound 7) for the inhibition of MMP-13 is 2.3 µM, some 100-fold less potent than its inhibition of MMP-3. UK-370106 is found to be inactive (IC ₅₀ > 100 µM) vs zinc metalloproteases PCP and TACE and possesses the following inhibitory potencies vs MMP-2 (IC ₅₀ of 34.2 µM), MMP-7 (IC ₅₀ of 5.8 µM), MMP-8 (IC ₅₀ of 1.75 µM), MMP-9 (IC ₅₀ of 30.4 µM) and MMP-14 (IC ₅₀ of 66.9 µM).
UK-370106 potently inhibits cleavage of [ ³ H]-fibronectin by MMP-3 (IC ₅₀ of 320 nM) but does not inhibit cleavage of [ ³ H]-gelatin by either MMP-2 or -9 up to the highest concentration tested (100 µM).
UK-370106 is not cytotoxic to, nor affected proliferation of, fibroblasts, keratinocytes, or endothelial cells at 50-100 µM in vitro.

Following iv (rat; 2 mg/kg) or topical administration to dermal wounds (rabbit), UK-370106 (compound 7) is cleared rapidly (t _1/2 = 23 min) from plasma, but slowly (t _1/2 approximately 3 days) from dermal tissue. In a model of chronic dermal ulcers, topical administration of UK-370106 for 6 days substantially inhibits MMP-3 ex vivo.