UK-370106 is a potent and selective inhibitor of MMP-3 (IC50 of 23 nM) and MMP-12 (IC50 of 42 nM), with greater potency than MMP-1, MMP-2, MMP-9 and MMP- 14 is more than 1200 times higher and about 100 times higher than MMP-13. UK-370106 potently inhibits [3H]-fibronectin cleavage by MMP-3 (IC50 of 320 nM) and has little effect on keratinocyte migration.

Physicochemical Properties

Molecular Formula	C₃₅H₄₄N₂O₅
Molecular Weight	572.73
Exact Mass	572.325
CAS #	230961-21-4
PubChem CID	9808181
Appearance	White to off-white solid powder
Density	1.123g/cm3
Boiling Point	802.689ºC at 760 mmHg
Flash Point	439.25ºC
Vapour Pressure	0mmHg at 25°C
Index of Refraction	1.56
LogP	6.892
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	15
Heavy Atom Count	42
Complexity	843
Defined Atom Stereocenter Count	3
SMILES	CC1=C(C=CC(=C1)CCC[C@H](CC(=O)O)C(=O)N[C@H](C(=O)N[C@H](COC)C2=CC=CC=C2)C(C)(C)C)C3=CC=CC=C3
InChi Key	NSMABJUGSNPHMN-BHYWQNONSA-N
InChi Code	InChI=1S/C35H44N2O5/c1-24-21-25(19-20-29(24)26-14-8-6-9-15-26)13-12-18-28(22-31(38)39)33(40)37-32(35(2,3)4)34(41)36-30(23-42-5)27-16-10-7-11-17-27/h6-11,14-17,19-21,28,30,32H,12-13,18,22-23H2,1-5H3,(H,36,41)(H,37,40)(H,38,39)/t28-,30-,32-/m1/s1
Chemical Name	(3R)-3-[[(2S)-1-[[(1S)-2-methoxy-1-phenylethyl]amino]-3,3-dimethyl-1-oxobutan-2-yl]carbamoyl]-6-(3-methyl-4-phenylphenyl)hexanoic acid
Synonyms	UK370106 UK 370106
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ln Vitro	UK-370106 (Compound 7) has a potency of 2.3 µM to inhibit MMP-13, which is roughly 100 times lower than its potency to inhibit MMP-3. The zinc metalloproteases PCP and TACE were found to be inactive against UK-370106 (IC50 > 100 µM). Additionally, MMP-2 (IC50 of 34.2 µM), MMP-7 (IC50 of 5.8 µM), and MMP-8 Potency (IC50 of 1.75 µM), MMP-9 (IC50 of 30.4 µM), and MMP-14 (IC50 of 66.9 µM) were all inhibited [1]. Up to the highest dose tested (100 µM), UK-370106 potently inhibits [3H]-fibronectin cleavage by MMP-3 (IC50 of 320 nM), but not [3H]-gelatin cleavage by MMP-2 or -9[1]. At concentrations of 50–100 µM in vitro, UK-370106 is not cytotoxic to fibroblasts, keratinocytes, or endothelial cells and has no effect on their proliferation [1].
ln Vivo	UK-370106 (compound 7) was removed from cutaneous tissue slowly (t1/2 = 3 days) but quickly (t1/2 = 23 min) from plasma. Topical treatment of UK-370106 for 6 days effectively suppressed MMP-3 in vitro in a chronic skin ulcer model [1].
References	[1]. A potent, selective inhibitor of matrix metalloproteinase-3 for the topical treatment of chronic dermal ulcers. J Med Chem. 2003 Jul 31;46(16):3514-25. [2]. A novel series of highly selective inhibitors of MMP-3. Bioorg Med Chem Lett. 2007 Dec 15;17(24):6750-3. Epub 2007 Oct 17.

Solubility Data

Solubility (In Vitro)

DMSO : ~200 mg/mL (~349.20 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 5 mg/mL (8.73 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 5 mg/mL (8.73 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 5 mg/mL (8.73 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.7460 mL	8.7301 mL	17.4602 mL
	5 mM	0.3492 mL	1.7460 mL	3.4920 mL
	10 mM	0.1746 mL	0.8730 mL	1.7460 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.