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UCB9608

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Chemical Structure| 1616413-96-7 同义名 : -
CAS号 : 1616413-96-7
货号 : A789351
分子式 : C20H26N8O2
纯度 : 99%+
分子量 : 410.473
MDL号 : MFCD01744844
存储条件：

粉末 Keep in dark place,Inert atmosphere,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 65 mg/mL(158.35 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
描述 The phosphatidylinositol 4-kinases (PI4Ks) play prominent roles in compartment identity. PI4KIIIβ is one of four mammalian PI4K enzymes that phosphorylate phosphatidylinositol to generate phosphatidylinositol 4-phosphate (PI4P). PI4KIIIβ localizes primarily at the Golgi and is essential for Golgi formation and function. PI4KIIIβ activity is essential for replication of a range of RNA viruses, including enteroviruses, SARS coronavirus, and hepatitis C virus[1]. UCB9608 is a potent, selective and orally active PI4KIIIβ inhibitor, with an IC50 value of 11 nM. UCB9608 is selective for PI4KIIIβ over PI3KC2 α, β, and γ lipid kinases. UCB9608 inhibits human mixed lymphocyte reaction, with an IC50 value of 37 nM. UCB9608 improves metabolic stability and exhibits excellent pharmacokinetic profile, acts as a potent immunosuppressive agent[2]. UCB9608 had very low CLb, commensurate with its low CLint in MLM, leading to a half-life of 1.4 h, with high bioavailability, and low inter-individual variability. UCB9608 could achieve high and consistently reproducible exposures in Balb/C mice. It could also prevent the rejection of a heterotopic murine cardiac allograft at a dose of 5 mpk. The excellent ADME properties of UCB9608 make it an ideal molecule to develop the understanding of the role of this novel class of PI4KIIIβ inhibitors on immune cell activation[2].
作用机制 The amino pyrimidine of UCB9608 makes a bidentate interaction with the Val613 backbone. The urea NH and carbonyl of UCB9608 form H-bonds with the main-chain Gly675 carbonyl and the side-chain NH2 of Asn390 respectively.
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.44mL

0.49mL

0.24mL

12.18mL

2.44mL

1.22mL

24.36mL

4.87mL

2.44mL
参考文献

[1]Burke JE, Inglis AJ, Perisic O, Masson GR, McLaughlin SH, Rutaganira F, Shokat KM, Williams RL. Structures of PI4KIIIβ complexes show simultaneous recruitment of Rab11 and its effectors. Science. 2014 May 30;344(6187):1035-8. doi: 10.1126/science.1253397. PMID: 24876499; PMCID: PMC4046302.

[2]Reuberson J, Horsley H, Franklin RJ, Ford D, Neuss J, Brookings D, Huang Q, Vanderhoydonck B, Gao LJ, Jang MY, Herdewijn P, Ghawalkar A, Fallah-Arani F, Khan AR, Henshall J, Jairaj M, Malcolm S, Ward E, Shuttleworth L, Lin Y, Li S, Louat T, Waer M, Herman J, Payne A, Ceska T, Doyle C, Pitt W, Calmiano M, Augustin M, Steinbacher S, Lammens A, Allen R. Discovery of a Potent, Orally Bioavailable PI4KIIIβ Inhibitor (UCB9608) Able To Significantly Prolong Allogeneic Organ Engraftment in Vivo. J Med Chem. 2018 Aug 9;61(15):6705-6723. doi: 10.1021/acs.jmedchem.8b00521. Epub 2018 Jul 19. PMID: 29952567.