BMS-814580 是一种具有口服活性的、高效的MCHR1抑制剂，Ki值为 16.9 nM。 BMS-814580 具有抗肥胖活性。
| 生物活性 | BMS-814580 is an orally active, highly efficaciousMCHR1inhibitor with aKiof 16.9 nM against hMCHR1. BMS-814580 shows antiobesity activities[1]. |
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体外研究
(In Vitro) | BMS-814580 (3.0 μM; 10 min) shows stability with 90%, 95% and 100% remaining in human, rat and mouse liver microsomes, respectively[1].
BMS-814580 displays modest in vitro ion channel inhibition of 43%, 21%, and 15%, respectively, for hERG, Na (4 Hz), and L-type Ca channels at 10 μM[1].
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体内研究
(In Vivo) | BMS-814580 (0-3 mg/kg; p.o.; once daily for 28 days) shows antiobesity activities in rats[1].
| Animal Model: | Obese male SD rats, chronic diet-induced obese (DIO) rat model[1] | | Dosage: | 0.03, 0.1, 0.3, 1 and 3 mg/kg | | Administration: | Orally administered as the phosphate prodrug, once daily for 28 days | | Result: | Dose dependently reduced body weight. |
| Animal Model: | Sprague-Dawley Rats[1] | | Dosage: | 10 mg/kg | | Administration: | Oral administration, once | | Result: | Pharmacokinetics (PK) and Pharmacodynamics (PD) Data: Plasma and Brain Concentrations of Cyclic Tertiary Alcohols and the Effect on Body Weights in Sprague-Dawley Rats
| | | 8 h rat PK studyb | | 4-day PD studyc | day 4 parent compd | concn at 20 h | | compd | dosed asa | AUC (μMoh) | brain (nM) | plasma (nM) | % weight loss | brain (nM) | plasma (nM) | | BMS-814580 | glycinate | 38.1 | 11330 | 4500 | 6.4d | 7955 | 12801 |
aRats were dosed orally with parent compound or a prodrug; prodrugs doses were adjusted to parent compounds. Vehicle = 0.5% Methocel, 0.1% Tween 80, 99.4% distilled water.bDose = 10 mg/kg; plasma and brain concentrations are reported 8 h after dose, n = 2.cCompounds were dosed at 3, 10, and 30 mg/kg orally once a day for 4 days; weight loss data is reported only for the 10 mg/kg dose, n = 8; reduction in body weight is reported as % change from baseline body weight compared to vehicle treated animals. NT = not tested.dNo biliary lesions were seen in this model. |
| Animal Model: | Sprague-Dawley Rats[1] | | Dosage: | 10 mg/kg (phosphate prodrug) or 1 mg/kg | | Administration: | Oral (phosphate prodrug) or intravenous administration (Pharmacokinetic Analysis) | | Result: | Pharmacokinetics Data for BMS-814580 in Rata
| species | compd (mg/kg) | route of admin | Cmax(μM) | Tmax(h) | AUC0–∞(μMoh) | T1/2(h) | CL (mL/min/kg) | Vss(L/kg) | F (%) | | rat | BMS-814580 (1) | iv | | | 11.5 | >24 | 0.9 | 4.1 | | | BMS-814580 phosphate (10) | po | 4.0 | 6.7 | 107 | | | | 54 |
aVehicles: iv, PEG400/DMAC/water (70:5:25); po, Methocel/Tween80/water (0.5:0.1:99.4). |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | Please store the product under the recommended conditions in the Certificate of Analysis. |
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