Plinabulin (NPI-2358) (Synonyms: NPI-2358) |
| Catalog No.GC10235 |
Plinabulin (NPI-2358) (NPI-2358) is a vascular disrupting agen (VDA) against tubulin-depolymerizing with an IC50 of 9.8 nM against HT-29 cells. Plinabulin (NPI-2358) binds the colchicine binding site of β-tubulin preventing polymerization and has potent inhibitory to tumor cells.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 714272-27-2
Sample solution is provided at 25 µL, 10mM.
;)
,-1-7$$$37316672.jpg');)
;)
;)
$$$36806353.jpg');)
;33(7)%EF%BC%9A546-561$$$37156877.jpg');)
;)
;)
;)
%201124-1138.$$$35908550.jpg');)
%20766-780.$$$37100057.jpg');)
%20418-432.$$$36893736.jpg');)
%EF%BC%9A-240-255.$$$35108512.jpg');)
533-545$$$36543525.jpg');)
%201-13.$$$36600053.jpg');)
;)
The IC50 values of NPI-2358 is 9.8 ± 2.4 nmol/l, 18 ± 5 nmol/l, 13 ± 1 nmol/l, 14 ± 2 nmol/l, 18 ± 1 nmol/l and 11 nmol/l for HT-29, DU 145, PC-3, MDA-MB-231, NCl-H292 and Jurkat cell lines, respectively[1].
Plinabulin (NPI-2358) is a vascular disrupting agent which binds to the colchicine-binding site of tubulin. NPI-2358 could destabilize tumor vascular endothelial architectural resulting in selective collapse of established tumor vasculature [1].
In vitro: NPI-2358 exhibited anti-tumor activity against various human tumor cell lines. In proliferating human umbilical vein endothelial cells (HUVECs), administration of NPI-2358 at 10 nmol/l induced tubulin depolymerization within 30 min [1]. In an in-vitro model of tumor vascular collapse, NPI-2358 increased HUVEC monolayer permeability in a dose-dependent manner. Plinabulin had also shown the in-vitro cytotoxic activity with IC50 values of 11 ± 5 nmol/l and 4.3 ± 2.2 nmol/l for MES-SA and HL-60 tumor cell lines, respectively[1].
In vivo: In the foot implanted C3H mammary carcinomas or leg implanted KHT sarcomas mice model, 7.5 mg/kg plinabulin (intraperitoneally injected) significantly reduced the transfer constant (K(trans)) and the initial area under curve (IAUC) within 1 hour after injection, reaching a lowest point at 3 h, but returning to normal within 24 h. A dose-dependent decrease in IAUC and K(trans) was seen at 3 h. 12.5 mg/kg and 1.5 mg/kg NPI-2358 showed significant anti-tumour effects in the C3H tumours and the KHT sarcoma, respectively .
Clinical trials: In patients evaluated at a dose of 30 mg/m², tumor blood flow (Ktrans) showed a 16% to 82% decrease. The half-life of NPI-2358 was 6.06 ± 3.03 hours, clearance was 30.50 ± 22.88 L/h, and distributive volume was 211 ± 67.9 L.
References:
Nicholson B1, Lloyd GK, Miller BR, Palladino MA, Kiso Y, Hayashi Y, Neuteboom ST. NPI-2358 is a tubulin-depolymerizing agent: in-vitro evidence for activity as a tumor vascular-disrupting agent.Anticancer Drugs. 2006 Jan; 17(1):25-31.
Bertelsen L B, Shen Y Y, Nielsen T, et al. Vascular effects of plinabulin (NPI-2358) and the influence on tumour response when given alone or combined with radiation[J]. International journal of radiation biology, 2011, 87(11): 1126-1134.
Millward M, Mainwaring P, Mita A, et al. Phase 1 study of the novel vascular disrupting agent plinabulin (NPI-2358) and docetaxel[J]. Investigational new drugs, 2012, 30(3): 1065-1073.
Average Rating: 5 (Based on Reviews and 29 reference(s) in Google Scholar.)
GLPBIO products are for RESEARCH USE ONLY. Please make sure your review or question is research based.
Required fields are marked with *