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SMI-4a

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Chemical Structure| 438190-29-5 同义名 : TCS-PIM-1-4a
CAS号 : 438190-29-5
货号 : A107880
分子式 : C11H6F3NO2S
纯度 : 99%+
分子量 : 273.231
MDL号 : MFCD01152003
存储条件：

粉末 Sealed in dry,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 105 mg/mL(384.29 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：

IP 2% DMSO+2% Tween80+40% PEG300+water 5 mg/mL clear

PO 0.5% CMC-Na 43 mg/mL suspension

生物活性
靶点

  • Pim1

    Pim1, IC50:17 nM
描述 Pim (provirus integration site for Moloney murine leukemia virus) family proteins are highly conserved serine/threonine kinases implicated in transcription, translation, cell cycle, survival, and drug resistance through the numerous targets. SMI-4a is a potent inhibitor of Pim1 with IC50 of 17 nM (measured by kinase activity assay), as well as shows modest potency to Pim-2. As BAD is a novel substrate of Pim-1, SMI-4a < 5 μM caused dose-dependent reduction of p-BAD in prostate and hematopoietic cells tested. Treatment with 5 μM SMI-4a for 72 h showed various degree of growth inhibition (10-40%) of PC3, DU145, LNCaP, U937, K562 and MV4;11 cells cultured in media containing 10% FBS. Because SMI-4a showed to be serum-bound, it was found that DU145 cells became considerably more sensitive under serum-free conditions. For many substrates of Pim-1 play a role in cell cycle progression, as prediction, treatment with 5 μM SMI-4a for 72 h caused a significant G1 cell cycle arrest of DU145 cells growing in 2% serum and MV4;11 cells plated in 10% serum, as well as a considerable amount of apoptosis (sub-G1 29.2%) of 22Rv1 cells cultured under serum starvation condition. The translocation of p27Kip1 to the nucleus and reduced Cdk2 activity (shown by decreased p-H1) can also observed in K562 cells cultured in RPMI containing 10% FCS after treatment with SMI-4a. SMI-4a can synergize with rapamycin to cause significant growth inhibition, as well as decreased phosphorylation level of 4E-BP1 of MV4;11 and FDCP1 (IL-3 dependent) cells[1]. Combination treatment of ABT-737 (50 mg/kg; i.p., QD) and SMI-4a (60 mg/kg, oral gavage, BID) for 16 days significantly reduce the tumor growth of LNCaP xenograft model[2].
作用机制 SMI-4a can compete with respect to ATP, suggesting that it may bind within the ATP-binding pocket of the kinase.[1]
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
DLD-1 cell Function assay 96 h Inhibition of growth of DLD-1 cell line after 96 hours of exposure time with the compound dissolved in DMSO, IC50=17.8 μM 15993594
HCT116 cell Function assay 72 h Inhibition of growth of HCT116 cell line after 72 hours of exposure time with the compound dissolved in DMSO, IC50=48.8 μM 15993594
HEK293T cells 0.5 μM Function assay 1 h Inhibition of human recombinant Flag-Pim1 autophosphorylation expressed in HEK293T cells labeled with [32PO4] at 0.5 uM after 1hr by Western blotting 19072652
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

3.66mL

0.73mL

0.37mL

18.30mL

3.66mL

1.83mL

36.60mL

7.32mL

3.66mL
参考文献

[1]Song JH, Kraft AS, et al. Pim kinase inhibitors sensitize prostate cancer cells to apoptosis triggered by Bcl-2 family inhibitor ABT-737. Cancer Res. 2012 Jan 1;72(1):294-303.

[2]Beharry Z, Zemskova M, et al. Novel benzylidene-thiazolidine-2,4-diones inhibit Pim protein kinase activity and induce cell cycle arrest in leukemia and prostate cancer cells. Mol Cancer Ther. 2009 Jun;8(6):1473-83.

[3]Lei C, Da-lun L, et al. Inhibition of autophagy enhances SMI-4a-induced growth inhibition and apoptosis of melanoma cells. TJPR. 2018 Mar; 17 (3): 401-407.

[4]Lin YW, Beharry ZM, et al. A small molecule inhibitor of Pim protein kinases blocks the growth of precursor T-cell lymphoblastic leukemia/lymphoma. Blood. 2010 Jan 28;115(4):824-33.

[5]Jiang W, Chen Y, et al. Pim-1 inhibitor SMI-4a suppresses tumor growth in non-small cell lung cancer via PI3K/AKT/mTOR pathway. Onco Targets Ther. 2019 Apr 23;12:3043-3050.

[6]Lv DL, Chen L, et al. Ginsenoside G-Rh2 synergizes with SMI-4a in anti-melanoma activity through autophagic cell death. Chin Med. 2018 Feb 21;13:11.