UMI-77

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Chemical Structure| 518303-20-3 同义名 : -
CAS号 : 518303-20-3
货号 : A102389
分子式 : C18H14BrNO5S2
纯度 : 97%
分子量 : 468.341
MDL号 : MFCD03471890
存储条件：

Pure form Keep in dark place,Inert atmosphere,Room temperature

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

DMSO: 30 mg/mL(64.06 mM)，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：

5% DMSO+30% PEG 300+dd water 6 mg/mL

生物活性
靶点

  • Mcl-1

    Mcl-1, Ki:490 nM
描述 Mcl-1 (Myeloid cell leukemia-1) is an anti-apoptotic protein, which is a member of the Bcl-2 family. Mcl-1 is involved in the regulation of apoptosis versus cell survival, and in the maintenance of cell viability but not of proliferation. Mcl-1 mediates its effects by interactions with a number of other regulators of apoptosis[3]. UMI-77 is a Mcl-1 inhibitor. In FP-based binding assays, UMI-77 potently and selectively displaced fluorescent labeled BID-BH3 peptide from Mcl-1 protein. UMI-77 bound to the BH3 binding pocket of Mcl-1 and the Ki value was 0.49 μM[4]. In a pull-down assay, starting from the concentration of 10 μM , UMI-77 dose-dependently inhibited the interactions between BL-Noxa and cellular Mcl-1 in 2LMP cell lysates. In a SPR-based binding assay, it was reported that UMI-77 dose-dependently inhibited the binding of Mcl-1 to Bax with IC50 value of 1.43 μM. UMI-77 inhibited the growth of BxPC-2 and Panc-1 cells with IC50 values of 3.4 μM and 4.4 μM, respectively[4]. UMI-77 incubated at the concentrations of 3 μM or 10 μM for 48h induced apoptosis in esophageal squamous cell carcinoma KYSE150 and KYSE510 cells, as evidenced by cleavage of caspase-3 and PARP[5]. In BxPC-3 xenograft model established in SCID mice, UMI-77 administrated i.v. at the dose of 60 mg/kg for a total of 10 doses significantly inhibited tumor growth[4].
作用机制 UMI-77 is a Mcl-1 inhibitor. Docking and spectroscopy studies revealed that UMI-77 bound to the BH3 binding pocket of Mcl-1[4].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.14mL

0.43mL

0.21mL

10.68mL

2.14mL

1.07mL

21.35mL

4.27mL

2.14mL
参考文献

[1]Liu JW, Zhu ZC, ET AL. UMI-77 primes glioma cells for TRAIL-induced apoptosis by unsequestering Bim and Bak from Mcl-1. Mol Cell Biochem. 2017 Aug;432(1-2):55-65.

[2]Abulwerdi F, Liao C, et al. A novel small-molecule inhibitor of mcl-1 blocks pancreatic cancer growth in vitro and in vivo. Mol Cancer Ther. 2014 Mar;13(3):565-75.

[3]Bingle CD, Craig RW, Swales BM, Singleton V, Zhou P, Whyte MK. Exon skipping in Mcl-1 results in a bcl-2 homology domain 3 only gene product that promotes cell death. J Biol Chem. 2000 Jul 21;275(29):22136-46.

[4]Aboukameel A, Mady AS, Gulappa T, Cierpicki T, Owens S, Zhang T, Sun D, Stuckey JA, Mohammad RM, Nikolovska-Coleska Z. A novel small-molecule inhibitor of mcl-1 blocks pancreatic cancer growth in vitro and in vivo. Mol Cancer Ther. 2014 Mar;13(3):565-75.

[5]Yu X, Li W, Xia Z, Xie L, Ma X, Liang Q, Liu L, Wang J, Zhou X, Yang Y, Liu H. Targeting MCL-1 sensitizes human esophageal squamous cell carcinoma cells to cisplatin-induced apoptosis. BMC Cancer. 2017 Jun 28;17(1):449.