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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Paragraph 0051; 0052, (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.
Preparation and purification method of high-purity Plinabulin compound
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Paragraph 0029, (2017/08/31)
The invention provides a preparation and purification method of high-purity Plinabulin compound, which aims at mainly removing a trans-isomer. The preparation and purification method has the advantages that (3Z,6Z)-3-benzylidene-6-((5-tert-butyl-1H-imidazole-4-yl)methylene)piperazine-2,5-diketone monohydrate and (3Z,6Z)-3-benzylidene-6-((5-tert-butyl-1H-imidazole-4-yl)deuterated methylene)piperazine-2,5-diketone monohydrate are prepared; the purity of the prepared product is higher than 99.5%, and the content of the trans-isomer is smaller than 0.1%. The invention also relates to the preparation and purification of important intermediates, such as 5-(tert-butyl)-1H-imidazole-4-ethyl formate and 1,4-diacetylpiperazine-2,5-diketone. The preparation and purification method has the advantages that the production cost is reduced, the pos-treatment difficulty is decreased, and the technology more meets the requirements of industrialized production.
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
