714272-27-2 Usage
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 .
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.
Check Digit Verification of cas no
The CAS Registry Mumber 714272-27-2 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 7,1,4,2,7 and 2 respectively; the second part has 2 digits, 2 and 7 respectively.
Calculate Digit Verification of CAS Registry Number 714272-27:
(8*7)+(7*1)+(6*4)+(5*2)+(4*7)+(3*2)+(2*2)+(1*7)=142
142 % 10 = 2
So 714272-27-2 is a valid CAS Registry Number.
InChI:InChI=1S/C19H20N4O2/c1-19(2,3)16-13(20-11-21-16)10-15-18(25)22-14(17(24)23-15)9-12-7-5-4-6-8-12/h4-11H,1-3H3,(H,20,21)(H,22,25)(H,23,24)/b14-9-,15-10-
714272-27-2Relevant articles and documents
Plinabulin compound polycrystalline type and preparation method thereof
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, (2017/08/31)
The invention provides a plinabulin compound polycrystalline type and a preparation method thereof, and particularly relates to a polycrystalline type of (3Z,6Z)-3-benzylidene-6-((5-tert-butyl-1H-imidazole-4-yl) methylene)piperazidine-2,5-diketone and a preparation method thereof. Three kinds of crystalline types beta, gamma and delta are developed on the basis of the crystalline type alpha of (3Z,6Z)-3-benzylidene-6-((5-tert-butyl-1H-imidazole-4-yl) methylene)piperazidine-2,5-diketone, wherein the three kinds of crystalline types beta, gamma and delta can be prepared into monocrystallines; the three kinds of crystalline types have the advantages of clear conformation, high purity and high method repeatability; the important significance is realized on implementation of plinabulin biological effectiveness study and dosage form variety development.
Acid addition salt of deuteration dehydrogenation phenyl plinabulin compound and application thereof to anti-tumor medicine preparation
-
, (2017/10/31)
The invention discloses and provides an acid addition salt of a deuteration dehydrogenation phenyl plinabulin compound and application thereof to anti-tumor medicine preparation. The invention discloses and provides a preparation process of (3Z,6Z)-3-benzylidene-6-((5-tert-butyl-1H-imidazole-4-yl)deuteration methylene) piperazidine-2,5-diketone compound acid addition salt. The salifying compound aims at obviously improving the solubility and the bioavailability of the active ingredients of the compound; further, the sufficient embodiment and application are achieved in aspects of curative effect and dosage form selection of the anti-tumor medicine.
Prodrug study of plinabulin using a click strategy focused on the effects of a replaceable water-solubilizing moiety
Yakushiji, Fumika,Tanaka, Hironari,Muguruma, Kyohei,Iwahashi, Takahiro,Yamazaki, Yuri,Hayashi, Yoshio
experimental part, p. 877 - 881 (2012/08/08)
Plinabulin (1) is a potent anti-microtubule agent, however, its low water solubility has to be improved for the advantage in pharmacokinetics and chemotherapy. In this report, the replaceable water-solubilizing moiety of the water-soluble prodrug of plina
