IPI549 - PI3Kγt抑制剂d - 生命科学试剂 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEIPI549Cat. No.: HY-100716CAS No.: 1693758-51-8分式: CHNO分量: 528.56作靶点: PI3K作通路: PI3K/Akt/mTOR储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 DMSO : 15 mg/mL (28.38 mM; Need ultrasonic and warming)Ma

2、ss Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 1.8919 mL 9.4597 mL 18.9193 mL5 mM 0.3784 mL 1.8919 mL 3.7839 mL10 mM 0.1892 mL 0.9460 mL 1.8919 mL请根据产品在不同溶剂中的溶解度，选择合适的溶剂配制储备液，并请注意储备液的保存式和期限。体内实验 请根据您的实验动物和给药式选择适当的溶解案，配制前请先配制澄清的储备液，再依次添加助溶剂(为保证实验结果的可靠性，体内实验的作液，建议您现现配，当天使；澄清的储备液可以根据储存条件，适当保存；以下溶剂前的百

3、分 指该溶剂在您配制终溶液中的体积占)：1. 请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (4.73 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (4.73 mM); Clear solutionBIOLOGICAL ACTIVITY1/3 Master of Small Molecules 您边的抑制剂师www.MedChemE物活性 IPI549种有效的选择性 PI3K 抑制剂，

4、IC50 为 16 nM。IC50 & Target PI3K PI3K PI3K3.2 M (IC50) 3.5 M (IC50) 16 nM (IC50)体外研究 IPI-549 inhibits PI3K with IC50 of 16 nM, with 100-fold selectivity over other lipid and protein kinases (PI3K IC50=3.2 M, PI3K IC50=3.5 M, PI3K IC508.4 M). IPI549 is evaluated for activity across all Class IPI3K iso

5、forms. The binding affinity of IPI549 for PI3K- is determined by measuring the individual ratesconstants and for PI3K-, and using equilibrium fluorescent titration. IPI549 is found to be a remarkablytight binder to PI3K with a Kd of 290 pM and 58-fold weaker affinity for other Class I PI3K isoforms

6、(PI3KKd=17 nM, PI3K Kd=82 nM, PI3K Kd=23 M). In PI3K-, -, -, and - dependent cellular phospho-AKTassays, IPI549 demonstrates excellent PI3K- potency (IC50=1.2 nM) and selectivity against other Class IPI3K isoforms (146-fold). Cellular IC50s for Class I PI3K (250 nM), PI3K (240 nM), PI3K (1.2 nM), PI

7、3K (180 nM) are determined in SKOV-3, 786-O, RAW 264.7, and RAJI cells, respectively, by monitoringinhibition of pAKT S473 by ELISA. Furthermore, IPI549 dose dependently inhibits PI3K dependent bonemarrow-derived macrophage (BMDM) migration. IPI549 is also found to be selective against a panel of 80

8、GPCRs, ion channels, and transporters at 10 M 1.体内研究 IPI-549 demonstrates favorable pharmacokinetic properties and robust inhibition of PI3K- mediatedneutrophil migration. In vivo (mice, rats, dog, and monkeys), IPI-549 has excellent oral bioavailability, lowclearance, and distributed into tissues w

9、ith a mean volume of distribution of 1.2 L/kg. Overall, IPI-549 has afavorable pharmacokinetic profile to allow potent and selective inhibition of PI3K- in vivo. The t1/2 of IPI-549for mouse, rat, dog and monkey is 3.2, 4.4, 6.7 and 4.3 h, respectively. IPI-549 significantly reducesneutrophil migrat

10、ion in a dose dependent manner in this model when administered orally at all of the testeddoses 1.PROTOCOLAnimal C57BL/6J and Balb/c mice (6 to 8 weeks old) are used in this study. On day 0 of the experiments, tumor cellsAdministration 2 are injected intradermally (i.d.) in the right flank. IPI-549

11、is administered by oral gavage once a day at 15mg/kg. Treatment is initiated on day 7 ending on day 21 post tumor implant. Control groups receive vehicle(5% NMP, 95% PEG). Tumors are measured every second or third day with a caliper, and the volume(lengthwidthheight) is calculated. Animals are eutha

12、nized for signs of distress or when the total tumorvolume reaches 2500 mm3. Finally, Tumors are isolated, and frozen until needed 2.MCE has not independently confirmed the accuracy of these methods. They are for reference only.户使本产品发表的科研献 Brain Res Bull. 2019 Jun 17;150:272-280.See more customer val

13、idations on HYPERLINK / www.MedChemEREFERENCES2/3 Master of Small Molecules 您边的抑制剂师www.MedChemE1. Evans CA, et al. Discovery of a Selective Phosphoinositide-3-Kinase (PI3K)- Inhibitor (IPI-549) as an Immuno-Oncology ClinicalCandidate. ACS Med Chem Lett. 2016 Jul 22;7(9):862-7.2. De Henau O, et al. Overcoming resistance to checkpoint blockade therapy by targeting PI3K in myeloid cells. Nature. 2016 Nov17;539(7629):443-447.M