| Identification | Back Directory | [Name]
Plinabulin(NPI-2358) | [CAS]
714272-27-2 | [Synonyms]
CS-829
NPI-2358
EOS-62083
Plinabulin
Plinabulin, >=98%
NPI-2358; NPI 2358
Plinabulin(NPI-2358)
NPI-2358 (Plinabulin)
Plinabulin(NPI-2358)USP/EP/BP
(3Z,6Z)-3-benzylidene-6-((5-tert-butyl-1H-imidazol-4-yl)methylene)piperazine-2,5-dione
(3Z，6Z)-3-benzylidene-6-[(5-tert-butyl-1H-imidazol-4-yl)methylidene]piperazine-2，5-dione
(Z)-3-((Z)-benzylidene)-6-((5-(tert-butyl)-1H-imidazol-4-yl)methylene)piperazine-2,5-dione
(3Z,6Z)-3-[(5-tert-Butyl-1H-imidazol-4-yl)methylene]-6-(phenylmethylene)-2,5-piperazinedione
3-(Z)-benzylidene-6-(((Z)-5-tert-butyl-1H-imidazol-4-yl)methylene)-piperazine-2,5-dione monohydrate
2,5-Piperazinedione, 3-[[5-(1,1-dimethylethyl)-1H-imidazol-4-yl]methylene]-6-(phenylmethylene)-, (3Z,6Z)-
Plinabulin
(3Z,6Z)-3-[(5-tert-Butyl-1H-imidazol-4-yl)methylene]-6-(phenylmethylene)-2,5-piperazinedione
(3Z,6Z)-3-[(5-tert-Butyl-1H-imidazol-4-yl)methylene]-6-(phenylmethylene)-2,5-piperazinedione Plinabulin (NPI-2358) | [Molecular Formula]
C19H20N4O2 | [MDL Number]
MFCD18074510 | [MOL File]
714272-27-2.mol | [Molecular Weight]
336.39 |
| Hazard Information | Back Directory | [Definition]
ChEBI: Plinabulin is a member of the class of 2,5-diketopiperazines that is piperazine-2,5-dione substituted by benzylidene and (5-tert-butyl-1H-imidazol-4-yl)methylidene groups at positions 3 and 6, respectively. It is a vascular disrupting agent and a microtubule destabalising agent which was in clinical trials (now discontinued) for the treatment of non-small cell lung cancer. It has a role as a microtubule-destabilising agent, an antineoplastic agent, an apoptosis inducer and an angiogenesis inhibitor. It is a member of 2,5-diketopiperazines, a member of imidazoles, a member of benzenes and an olefinic compound. | [Biological Activity]
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 . | [target]
Tubulin | [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. |
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