DC Chemicals Limited
China
Product Name: AMG-3969
Price: $750.0/100mg $1300.0/250mg $2600.0/1g
Purity: 98.0%
Stocking Period: 3 Day
Contact: Tony Cao

1361224-53-4

1361224-53-4 structure

Name: AMG-3969
Chemical Name: 2-{4-[(2S)-4-[(6-Amino-3-pyridinyl)sulfonyl]-2-(1-propyn-1-yl)-1-piperazinyl]phenyl}-1,1,1,3,3,3-hexafluoro-2-propanol
CAS Number: 1361224-53-4
Molecular Formula: C₂₁H₂₀F₆N₄O₃S
Molecular Weight: 522.464
Catalog: Signaling Pathways Metabolic Enzyme/Protease Glucokinase
Create Date: 2018-02-22 12:16:56
Modify Date: 2024-01-11 19:03:44
AMG-3969 is a potent glucokinase-glucokinase regulatory protein interaction (GK-GKRP) disruptor with an IC50 of 4 nM.

Name	2-{4-[(2S)-4-[(6-Amino-3-pyridinyl)sulfonyl]-2-(1-propyn-1-yl)-1-piperazinyl]phenyl}-1,1,1,3,3,3-hexafluoro-2-propanol
Synonyms	2-{4-[(2S)-4-[(6-Amino-3-pyridinyl)sulfonyl]-2-(1-propyn-1-yl)-1-piperazinyl]phenyl}-1,1,1,3,3,3-hexafluoro-2-propanol Benzenemethanol, 4-[(2S)-4-[(6-amino-3-pyridinyl)sulfonyl]-2-(1-propyn-1-yl)-1-piperazinyl]-α,α-bis(trifluoromethyl)- AMG-3969

Description	AMG-3969 is a potent glucokinase-glucokinase regulatory protein interaction (GK-GKRP) disruptor with an IC50 of 4 nM.
Related Catalog	Signaling Pathways >> Metabolic Enzyme/Protease >> Glucokinase Research Areas >> Metabolic Disease
Target	IC50: 4 nM (GK-GKRP)[1]
In Vitro	AMG-3969 exhibits potent cellular activity with an EC50 of 0.202 μM and IC50 of 4 nM[1], [2]. It potently reverses the inhibitory effect of GKRP on GK activity and promotes GK translocation in vitro (isolated hepatocytes)[3].
In Vivo	AMG-3969 has good in vivo pharmacokinetic (PK) properties in rats (75%) and significantly lowers blood glucose levels in a dose-dependent manner db/db mice[1]. AMG-3969 (100 mg/kg) demonstrates significant reductions in blood glucose with robust efficacy (56% reduction) observed at the 8 h time point[2]. AMG-3969 demonstrates dose-dependent efficacy in three models of diabetes: diet induced obese (DIO), ob/ob and db/db mice; however,AMG-3969 is ineffective in lowering blood glucose in normoglycaemic C57BL/6 (B6) mice. AMG-3969 is highly effective in promoting carbohydrate substrate. AMG-3969 exhibits extended changes to carbohydrate oxidation as observed by increased respiratory exchange ratio into the next night and day after a single dose[3].
Animal Admin	Mice: Diabetic db/db mice are used in the study. At 8:00 AM, mice are bled via retro-orbital sinus puncture and blood glucose values are determined and used to randomize the animals in which their averages are similar, and only mice with blood glucose ranges between 300 and 500 mg/dL are included. Vehicle (2% hydroxypropyl methycellulose, 1% Tween 80, pH 2.2 adjusted with MSA) or AMG-3969 (10, 30, 100 mg/kg) are gavaged at 9:00 AM. Blood glucose is measured at 4, 6, or 8 h posttreatment. At each time point, a 15 μL sample of whole blood is analyzed for drug exposure[2].
References	[1]. Lloyd DJ, et al. Antidiabetic effects of glucokinase regulatory protein small-molecule disruptors. Nature. 2013 Dec 19;504(7480):437-40. [2]. Nishimura N, et al. Small molecule disruptors of the glucokinase-glucokinase regulatory protein interaction: 3. Structure-activity relationships within the aryl carbinol region of the N-arylsulfonamido-N'-arylpiperazine series. J Med Chem. 2014 Apr 10;57(7):3094-116. [3]. St Jean DJ Jr, et al. Small molecule disruptors of the glucokinase-glucokinase regulatory protein interaction: 2. Leveraging structure-based drug design to identify analogues with improved pharmacokinetic profiles. J Med Chem. 2014 Jan 23;57(2):325-38.

Density	1.6±0.1 g/cm3
Boiling Point	648.8±65.0 °C at 760 mmHg
Molecular Formula	C₂₁H₂₀F₆N₄O₃S
Molecular Weight	522.464
Flash Point	346.2±34.3 °C
Exact Mass	522.116028
LogP	4.51
Vapour Pressure	0.0±2.0 mmHg at 25°C
Index of Refraction	1.598
Storage condition	-20℃

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