Umbralisib

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Chemical Structure| 1532533-67-7 同义名 : TGR-1202;RP-5264
CAS号 : 1532533-67-7
货号 : A137762
分子式 : C31H24F3N5O3
纯度 : 99%+
分子量 : 571.549
MDL号 : MFCD28386165
存储条件：

Pure form Keep in dark place,Inert atmosphere,Store in freezer, under -20°C

In solvent -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 25 mg/mL(43.74 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：

IP 2% DMSO+2% Tween80+30% PEG300+water 1 mg/mL clear

PO 0.5% CMC-Na 35 mg/mL suspension

生物活性
靶点

  • p110δ

    PI3Kδ, IC50:22.2 nM
描述 Phosphoinositide-3 kinase (PI3K) is a kind of intracellular lipid kinase that frequently been activated in human cancers and thus been an attractive target. PI3K contains PI3Kα, β, δ and γ isoforms and RP-5264 is the inhibitor of PI3Kδ with IC50 value of 22.2 nM and EC50 value of 24.3 nM. RP-5264 could induce anti-FceR1 induced CD63 surface expression with EC50 value of 67nM as well as significant inhibit CD19+ or CD45R+ cell proliferation with concentration of 1000 nM. In multiple Myeloma resistant or sensitive cells, the drug showed IC50 values of 2975 and 3157 nM respectively. Furthermore, 50 mg/kg RP-5264 led to 80% inhibition of LPS induced CD45R in mice model. And 40% inhibitions of HL-60, THP-1, MOLT-4 and DLBCL cells were observed when treated with 300 nM RP-5264[1]. In L-540, KM-H2 and L-428 cells, RP-5264 could inhibit their proliferations and survivals with IC50 values of 11, 16 and 46 μM respectively. Furthermore, cell death in L-540 cells was significantly increased and modest cytotoxic effect was observed in KM-H2 and L-428 cells after exposure for longer time. RP-5264 could also quickly inhibit constitutive phosphorylation of Akt within one hour. When 10 μM RP-5264 combined with 10 ng/ml BV was used, a significant reduction of the cell proliferation and an increasing of apoptotic cell death in these cell lines were observed and accompanied by down-regulation of anti-apoptotic proteins Mcl-1 and Bcl-2. Besides, the combination of the two drugs also induced a marked G2/M accumulation and G0/G1 reduction, suggesting an early G2/M arrest followed by apoptotic cell death. Such an combined treatment could also increase cyclin A2 and CDK1 levels as well as phospho-CDK1, MPM-2 and phosphor-histone H3, and so did the microtubule assembly[2].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.75mL

0.35mL

0.17mL

8.75mL

1.75mL

0.87mL

17.50mL

3.50mL

1.75mL
参考文献

[1]Swaroop Vakkalanka, Srikant Viswanadha, et al. Abstract 3741: Inhibition of PI3Kα kinase by a selective small molecule inhibitor suppresses B-cell proliferation and leukemic cell growth.

[2]Locatelli SL, Careddu G, et al. The novel PI3K-δ inhibitor TGR-1202 enhances Brentuximab Vedotin-induced Hodgkin lymphoma cell death via mitotic arrest. Leukemia. 2016;30(12):2402-2405.