SNS-032 (BMS-387032) is a selective inhibitor of CDK2 (IC50: 48 nM ) and is 10- and 20-fold selective over CDK1/CDK4. It is also sensitive to CDK7/9 (IC50: 62 nM/4 nM), and no effect on CDK6.

CDK7:62 nM, CDK9:4 nM, CDK2:48 nM

SNS-032对CDK1和CDK4的敏感度较低，其IC50分别为480 nM和925 nM。无论预后指标和治疗历史如何，SNS-032均能有效杀灭体外的慢性淋巴细胞白血病细胞。与flavopiridol和roscovitine相比，SNS-032在抑制RNA合成和诱导凋亡方面更为有效。SNS-032的活性可逆，移除SNS-032后可重新激活RNA聚合酶II，导致Mcl-1的重新合成和细胞存活。[1] SNS-032抑制内皮细胞的三维毛细血管网络形成，完全阻止U87 mg细胞介导的HUVECs毛细血管形成。此外，SNS-032显著阻止两种细胞系中VEGF的产生，阻断VEGF从而抑制体外血管生成。预临床研究表明，SNS-032通过多种细胞系的细胞周期阻滞和凋亡诱导。[2] SNS-032通过抑制CDK2和CDK7阻断细胞周期，并通过抑制CDK7和CDK9抑制转录。SNS-032的活性不受人血清的影响。[3] SNS-032诱导剂量依赖性的annexin V染色和caspase-3活化增加。在分子水平上，SNS-032引起RNA聚合酶（RNA Pol）II的丝氨酸2和5的显著去磷酸化，并抑制CDK2和CDK9的表达以及CDK7的去磷酸化。[4]

SNS-032 在肿瘤共培养模型中防止了肿瘤细胞诱导的VEGF分泌。[2] 作为一种新型CDK抑制剂，SNS-032展现出更高的选择性和较低的细胞毒性，已被证明能够在实体肿瘤中延长疾病的稳定状态。[4]

Cell Titer-Glo (CTG) luminescent assay is performed to measure the growth curves of both HUVECs and U87 mg cells. U87 mg cells and HUVECs (2×103 cells/well) are seeded in a 96-well microplate in a final volume of 100 ml. After 24 hours, cells are treated with various doses of SNS-032 (0–0.5 mM) for 24, 48, or 72 hours. After completion of the treatment, 100 ml of CTG solution is added to each well and incubated for 20 minutes at room temperature in the dark. Lysate (50 ml) is transferred to a 96-well white plate, and luminescence is measured by POLARstar OPTIMA. Percent cell growth is calculated by considering 100% growth at the time of SNS-032 addition.(Only for Reference)