ChemicalBook CAS DataBase List 1031336-60-3

1031336-60-3

Name	trans-4-[4-(7-Aminopyrazolo[1,5-a]pyrimidin-6-yl)phenyl]cyclohexaneacetic acid
CAS	1031336-60-3
Molecular Formula	C20H22N4O2
MDL Number	MFCD22124521
Molecular Weight	350.41
MOL File	1031336-60-3.mol

Chemical Properties

density	1.39
storage temp.	Store at -20°C
solubility	DMSO : 66.67 mg/mL (190.26 mM; Need ultrasonic)
form	Powder
pka	4.72±0.10(Predicted)
color	White to off-white

Hazard Information

Uses

ABT-046 is a potent, selective, and orally active acyl CoA:diacylglycerol acyltransferase 1 (DGAT-1) inhibitor with IC50s of both 8 nM against human and mouse DGAT-1[1].

in vivo

ABT-046 (0.03-3 mg/kg; i.g.; once) significantly reduced postprandial triglycerides in CD-1 mice^[1].
ABT-046 (0.3 mg/kg; i.g.; once) abolishes the postprandial triglyceride excursion in diet-induced obesity mice^[1].

Animal Model:	Male CD-1 mice, postprandial hyperlipidemia model^[1]
Dosage:	0.03, 0.3, or 3 mg/kg
Administration:	Oral gavage, single dose
Result:	Showed a dose-dependent reduction in serum triglycerides starting at 0.03 mg/kg and increasing through the higher doses (40, 60, and 90% reduction from vehicle at 0.03, 0.3, and 3.0 mg/kg, respectively). The ascending pharmacodynamics correlated well with a linear increase in plasma exposure going from 0.03 to 3 mg/kg (C_2h = 0.033, 0.36, and 3.10 μg/mL at 0.03, 0.3, and 3.0 mg/kg, respectively).

Animal Model:	Male C57BL/6J diet-induced obesity (DIO) mice^[1]
Dosage:	0.3 mg/kg
Administration:	Oral gavage, single dose
Result:	Afforded a sustained reduction in serum triglyceride concentrations throughout the experiment.

Animal Model:

CD-1 mice and Sprague-Dawley rats^[1]

Dosage:

10 mg/kg or 5 mg/kg

Administration:

Intravenous injection or oral gavage (Pharmacokinetic Analysis)

Result:

Selected Pharmacokinetic Properties of ABT-046^a^[1]

	mouse (10 mg/kg)	rat (5 mg/kg)
	iv^b
T_1/2 (h)	4.6	3.8
V_ss (L/kg)	0.3	0.3
Clp (L/h/kg)	0.1	0.05
	po^b
T_1/2 (h)	5.1	5.6
C_max (μg/mL)	17.4	9.3
AUC (μg h/mL)	151	130
F (%)	78	91

^a All values are mean values ± SEMs (n = 3 unless specified otherwise).
^b 1% Tween-80 in water.

References

[1] Yeh VS, et al. Identification and preliminary characterization of a potent, safe, and orally efficacious inhibitor of Acyl-CoA: Diacylglycerol acyltransferase 1. J Med Chem. 2012 Feb 23;55(4):1751-1757. DOI:10.1021/jm201524g

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