UK 383367

UK-383367 is a potent and selective inhibitor of BMP-1 (procollagen C-proteinase; PCP) (IC50 = 44 nM). Bone morphogenic protein 1 (BMP1) is an enzyme responsible for the cleavage and maturation of growth factors and ECM proteins. The purpose of our study was to determine whether cultured human trabecular meshwork (TM) cells express BMP1, BMP1 expression is regulated by TGF-β2, BMP1 is biologically active, and BMP1 regulates LOX activity.

Product information

CAS Number: 348622-88-8

Molecular Weight: 324.38

Formula: C15H24N4O4

Synonym:

UK-383367

UK383367

Chemical Name: (R)-5-(6-cyclohexyl-1-(hydroxyamino)-1-oxohexan-3-yl)-1, 2, 4-oxadiazole-3-carboxamide

Smiles: NC(=O)C1N=C(ON=1)[C@@H](CC(=O)NO)CCCC1CCCCC1

InChiKey: ARJCBSRIPGJMAD-LLVKDONJSA-N

InChi: InChI=1S/C15H24N4O4/c16-13(21)14-17-15(23-19-14)11(9-12(20)18-22)8-4-7-10-5-2-1-3-6-10/h10-11,22H,1-9H2,(H2,16,21)(H,18,20)/t11-/m1/s1

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO: 65 mg/mL(200.38 mM). Water: Insoluble.

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

UK-383367 is effective at penetrating human skin. UK-383367 inhibits collagen deposition with IC50 of ~2 μM. UK-383367 has modest affinity for all the PDE-4 subtypes PDE-4a, PDE-4b, PDE-4c and PDE-4d with IC50 of 1.8 μM, 1.5 μM, 2.4 μM and 0.9 μM, respectively. UK-383367 is a weakly acidic compound and lipophilic.

In Vivo:

Plasma protein binding values for UK-383367 in rat, dog and human are 95%, 93% and 94%, respectively. UK-383367 following incubation in rat plasma results in the half-life of 49 min. UK-383367 following single intravenous administration (2 mg/kg) to rat results in the plasma clearance of 157 mL min−1 kg−1, the volume of distribution of 12 L kg−1, and an elimination half-life of 0.8  hour. UK-383367 following single intravenous administration (0.5 mg/kg) to dog results in the plasma clearance of 35 mL min−1 kg−1, the volume of distribution of 4.6 L kg−1, and an elimination half-life of 1.5 hours. UK-383367 following oral administration (2 mg/kg) to dog results in Cmax of 110 ng/mL, Tmax of 0.5-1.5 hour and oral bioavilability of 13%.

References:

1. Allan GA, et al. Xenobiotica, 2006, 36(5), 399-418.
2. Bailey S, et al. Bioorg Med Chem Lett, 2008, 18(24), 6562-6567.
3. Fish PV, et al. J Med Chem, 2007, 50(15), 3442-3456.

Products are for research use only. Not for human use.