Description
UAMC 0039 is a potent inhibitor of dipeptidyl peptidase 2 (DPP-2; IC
50 = 0.48 nM). It also inhibits DPP-4 (IC
50 = 165 μM). DPP-2 is thought to be involved in degradation of collagen, substance P, and some proline-containing neuropeptides.
in vivo
A dose dependent inhibition of DPPII but not of DPPIV is observed in the peripheral organs of both the rats and the mice (after oral administration) and the rabbits (after IV administration). UAMC00039 tested orally at 2 mg/kg does not cause signs of acute toxicity and does not cause any significant changes in the following functions that are evaluated: general behaviour, body temperature, respiration, bleeding time, blood pressure, urine volume, liver function, fasting glucose and gastrointestinal parameters like acidity, motility and irritation[1].
References
[1] KRISTEL SENTEN. γ-Amino-Substituted Analogues of 1-[(S)-2,4-Diaminobutanoyl]piperidine as Highly Potent and Selective Dipeptidyl Peptidase II Inhibitors[J]. Journal of Medicinal Chemistry, 2004, 47 11: 2906-2916. DOI:
10.1021/jm031122f[2] K J ANDERSEN J K M. Lysosomal heterogeneity of dipeptidyl peptidase II active on collagen-related peptides.[J]. Renal physiology and biochemistry, 1989, 12 1: 32-40. DOI:
10.1159/000173177[3] ROLF MENTLEIN Gemot S. Purification of Two Dipeptidyl Aminopeptidases II from Rat Brain and Their Action on Proline-Containing Neuropeptides[J]. Journal of Neurochemistry, 1989, 52 4: 1284-1293. DOI:
10.1111/j.1471-4159.1989.tb01877.x
