Plinabulin 是一种抗微管蛋白解聚肿瘤细胞的血管破坏剂，选择性地靶向并结合到微管蛋白的秋水仙碱结合位点，从而中断微管动力学的平衡。它对人肿瘤细胞系具有抑制作用，对 HT-29 细胞系的IC50值为 9.8 nM。

Plinabulin (NPI-2358) is a vascular disrupting agent (VDA) against tubulin-depolymerizing tumor cells ( IC50: 9.8-18 nM). Plinabulin selectively targets and binds to the colchicine-binding site of tubulin, thereby interrupting equilibrium of microtubule dynamics. This disrupts mitotic spindle assembly leading to cell cycle arrest at M phase and blockage of cell division.

NPI-2358时间和剂量依赖性地诱导肿瘤灌注降低.在携带人浆细胞移植瘤的鼠中,NPI-2358（7.5 mg/kg）可抑制肿瘤生长.与对C3H肿瘤的效果相比,NPI-2358对KHT肉瘤的作用更好,辐射处理可以增强对两种肿瘤的抗癌活性.

在人脐静脉内皮细胞中,NPI-2358（20 nM）可快速诱导微管蛋白解聚,并透过单细胞层。NPI-2358可使MM细胞停在有丝分裂早期,并诱导细胞死亡。NPI-2358与微管蛋白的秋水仙素结合位点结合,可有效抑制过量表达Pgp的人肿瘤细胞系,或使核Topo II催化活性降低（IC50：9.8-18 nM）。NPI-2358也还抑制微管形成及内皮细胞和MM细胞的迁移,造成肿瘤脉管系统功能失常。NPI-2358对有丝分裂停滞或MM细胞死亡具有诱导作用,但通过阻断JNK通路可使该作用失活。

The adherent cells are plated in 96-well flat-bottomed plates and allowed to attach for 24 hours at 37 °C. HL-60 and HL-60/MX2 cells are plated in 96-well plates on the day of NPI-2358 addition. Serially diluted NPI-2358 is added to cells at concentrations ranging from 2 pM to 20 μM. Cells treated with a final concentration of 0.25% (v/v) DMSO serves as the vehicle control. Cell viability is assessed 48 hours later by measuring the reduction of resazurin with a fluorimeter. The IC50 value is calculated.(Only for Reference)

714272-27-2

C19H20N4O2

336.395

普那布林;NPI-2358

H2O:<1 mgml
DMSO:50 mg/mL (148.6 mM)
Ethanol:<1 mgml
Powder: -20°C for 3 years
In solvent: -80°C for 2 years