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IACS-010759 HCl
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
IACS-010759 HCl图片
CAS NO:1807523-99-4
规格:≥98%
包装与价格:
包装价格(元)
5mg电议
10mg电议
25mg电议
50mg电议
100mg电议
250mg电议
500mg电议

产品介绍
理化性质和储存条件
Molecular Weight (MW) 599.03
FormulaC25H26ClF3N6O4S
CAS No.1807523-99-4 (HCl);
Storage-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)DMSO:> 60 mg/mL
Water: N/A
Ethanol: N/A
Chemical Name5-(5-methyl-1-(3-(4-(methylsulfonyl)piperidin-1-yl)benzyl)-1H-1,2,4-triazol-3-yl)-3-(4-(trifluoromethoxy)phenyl) -1,2,4-oxadiazole hydrochloride
SynonymsIACS010759 hydrochloride; IACS-010759; IACS 010759; IACS-10759 HCl; IACS 10759; IACS10759 HCl
实验参考方法
In Vitro

In vitro activity: IACS-10759 was identified as a potent and orally bioavailable inhibitor of complex I of oxidative phosphorylation (OXPHOS). In isolated mitochondria or permeabilized cells, ATP production or oxygen consumption was inhibited at single digit nM concentrations in the presence of malate/glutamate, but not succinate. More directly, IACS-10759 inhibited the conversion of NADH to NAD+ in an immunoprecipitated complex I assay at low nM concentrations. Using genetic and pharmacological approaches, the specific complex I subunit inhibited by IACS-10759 has been identified and the mechanism of complex I inhibition is being investigated. Importantly, IACS-10759 is orally bioavailable with excellent physicochemical properties in preclinical species and achieved significant in vivo efficacy with daily oral dosing of 10-25 mg/kg. Specifically, there was a>50 day extension of median survival in an orthotopic AML cell line xenograft and robust regression in DLBCL and GBM xenograft models. In light of these results, as well as its drug like profile IACS-10759 has entered IND enabling studies with first-in-human studies targeted for third quarter of 2015.


Kinase Assay: IACS-10759 inhibits the conversion of NADH to NAD+ in an immunoprecipitated complex I assay at low nM concentrations.

In Vivo

IACS-10759 is orally bioavailable with excellent physicochemical properties in preclinical species and achieves significant in vivo efficacy with daily oral dosing of 10-25 mg/kg. There is a>50 day extension of median survival in an orthotopic AML cell line xenograft and robust regression in DLBCL and GBM xenograft models.

Animal modelMice with DLBCL and GBM xenograft models
Formulation & Dosage10-25 mg/kg; oral; IACS-010759 was formulated in a 0.5% methylcellulose suspension and dosed by oral gavage according to described schedules. [1]
References

[1] Nat Med. 2018 Jul;24(7):1036-1046.

[2] Cancer Res 2015;75(15 Suppl):Abstract nr 4380. doi:10.1158/1538-7445.AM2015-4380.