IDH-305 - IDH1(R132) 抑制劑 - 生命科學(xué)試劑 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEIDH-305Cat. No.: HY-104036CAS No.: 1628805-46-8分式: CHFNO分量: 490.45作靶點: Isocitrate Dehydrogenase (IDH)作通路: Metabolic Enzyme/Protease儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實驗 DMSO : 150 mg/mL

2、(305.84 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲備液1 mM 2.0389 mL 10.1947 mL 20.3894 mL5 mM 0.4078 mL 2.0389 mL 4.0779 mL10 mM 0.2039 mL 1.0195 mL 2.0389 mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲備液，并請注意儲備液的保存式和期限。體內(nèi)實驗 請根據(jù)您的實驗動物和給藥式選擇適當(dāng)?shù)娜芙獍?，配制前請先配制澄清的儲備液，再依次添加助溶?為保證實

3、驗結(jié)果的可靠性，體內(nèi)實驗的作液，建議您現(xiàn)現(xiàn)配，當(dāng)天使；澄清的儲備液可以根據(jù)儲存條件，適當(dāng)保存；以下溶劑前的百分 指該溶劑在您配制終溶液中的體積占)：1. 請依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (5.10 mM); Clear solution2. 請依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (5.10 mM); Clear solution1/2 Master of Small Molecules 您邊的抑制劑師www.

4、MedChemEBIOLOGICAL ACTIVITY物活性 IDH-305種服性、突變選擇性和腦滲透性的 IDH1 抑制劑，靶向 IDH1 (R132) 突變。IDH-305 對突變體IDH1 亞型的選擇性野型 200 倍 (IC50= 27 nM (IDH1R132H), 28 nM (IDH1R132C), 6.14 M (IDH1WT)。IC50 & Target IC50: 27 nM (IDH1R132H), 28 nM (IDH1R132C), 6.14 M (IDH1WT) 1體外研究 IDH-305 inhibits HCT116-IDH1R132H+/- cells wit

5、h an IC50 of 24 nM 1.體內(nèi)研究 IDH-305 (30-300 mg/kg; p.o.; twice daily for 21 days) inhibits 2-HG production and 2-HG-dependent tumorgrowth of an IDH1 mutant PDX melanoma model 1.Animal Model: nu/nu mice (HMEX2838-IDH1R132C+/-PDX model) 1Dosage: 30, 100, 300 mg/kgAdministration: Oral gavage; twice daily

6、 for 21 daysResult: Resulted in 62-67% 2-HG reduction and significant anti-tumor activity at 100 mg/kg and97-99% 2-HG reduction and partial tumor regression of 32% at 300 mg/kg.REFERENCES1. Cho YS, et al. Discovery and Evaluation of Clinical Candidate IDH305, a Brain Penetrant Mutant IDH1 Inhibitor.

7、 ACS Med Chem Lett.2017 Sep 18;8(10):1116-1121.2. Courtney D DiNardo, et al. A Phase I Study of IDH305 in Patients with Advanced Malignancies Including Relapsed/Refractory AML andMDS That Harbor IDH1R132 Mutations. Blood, 128(22), 1073.McePdfHeightCaution: Product has not been fully validated for medical applications.For research use