Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/08/28 21:15:55」(JST)

wiki en

Neocarzinostatin is a macromolecular chromoprotein enediyne antibiotic with anti-tumoral activity secreted by Streptomyces macromomyceticus.

It consists of two parts, a labile chromophore (bicyclic dienediyne structure shown at right) and a 113 amino acid apoprotein to which the chromophore is tightly and non-covalently bound with high affinity (K_d ~ 10^-10 M). The chromophore is a very potent DNA-damaging agent; it is very labile and the role of the apoprotein is to protect it and release it to the target DNA. Opening of the epoxide under reductive conditions present in cells creates favorable conditions for a Bergman cyclization, leading to a diradical intermediate and eventually double DNA strand cleavage. Other members of the neocarzinostatin group of antibiotics are macromomycin, actinoxanthin, kedarcidin and maduropeptin.

As a medicine it is among the most potent, and in Japan only it has been used against liver cancer clinically.

References

^ Shoji Kobayashi, Makiko Hori, Guang Xing Wang, and Masahiro Hirama (2006). "Formal Total Synthesis of Neocarzinostatin Chromophore". J. Org. Chem. 71 (2): 636–644. doi:10.1021/jo052031o+S0022-3263(05)02031-1. PMID 16408974.

English Journal

A randomized phase II trial of intra-arterial chemotherapy using SM-11355 (Miriplatin) for hepatocellular carcinoma.

Okusaka T, Kasugai H, Ishii H, Kudo M, Sata M, Tanaka K, Shioyama Y, Chayama K, Kumada H, Yoshikawa M, Seki T, Saito H, Hayashi N, Shiratori K, Okita K, Sakaida I, Honda M, Kusumoto Y, Tsutsumi T, Sakata K.SourceHepatobiliary and Pancreatic Oncology Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan, tokusaka@ncc.go.jp.
Investigational new drugs.Invest New Drugs.2012 Oct;30(5):2015-25. Epub 2011 Dec 21.
Background SM-11355 is a platinum complex developed to treat hepatocellular carcinoma (HCC) via administration into the hepatic artery as a sustained-release suspension in iodized oil. We conducted a multicenter phase II trial in patients with HCC to evaluate the efficacy and safety of SM-11355, usi
PMID 22187203

RNF8 regulates assembly of RAD51 at DNA double-strand breaks in the absence of BRCA1 and 53BP1.

Nakada S, Yonamine RM, Matsuo K.SourceSchool of Medicine, Graduate School of Medicine, Osaka University.
Cancer research.Cancer Res.2012 Aug 3. [Epub ahead of print]
The tumor suppressor protein BRCA1 localizes to sites of DNA double-strand breaks (DSBs), promoting repair by homologous recombination (HR) through the recruitment of DNA damage repair proteins. In normal cells, HR largely depends on BRCA1. However, assembly of the pivotal HR regulator RAD51 can occ
PMID 22865450

Japanese Journal

腎癌肝転移に対するSMANCS/Lipiodol動注療法の経験

梅田俊,伊藤敬一,高橋英二 [他],木村文宏,住友誠,加地辰美,早川正道,浅野友彦
泌尿器科紀要 56(10), 543-549, 2010-10-00
… We treated liver metastases (8 target lesions) of RCC with stylene-maleic acid neocarzinostatin (SMANCS)/Lipiodol therapy. …
NAID 120002576707

Preparation of Neocarzinostatin Apoprotein Mutants and the Randomized Library on the Chromophore-Binding Cavity(Miscellaneous)

Tomioka Yoshihisa,Kisara Shigeki,Yoshizawa Saki [他],OZAWA Mika,SUZUKI Naoto,YAMAGUCHI Hiroaki,HISHINUMA Takanori,MIZUGAKI Michinao,GOTO Junichi
Biological & pharmaceutical bulletin 29(5), 1010-1014, 2006-05-01
… W39F, F52Y, S98G, S98A, and S98C mutants of the neocarzinostatin apoprotein (apo-NCS) were newly prepared and investigated their physicochemical properties. …
NAID 110005602231

Related Pictures

★リンクテーブル★

リンク元	「ネオカルチノスタチン」

「ネオカルチノスタチン」

Neocarzinostatin chromophore
	IUPAC name (1aS,5R,6R,6aE)-6-{[(2R,3R,4R,5R,6R)-4,5-Dihydroxy-6-methyl-3-(methylamino)tetrahydro-2H-pyran-2-yl]oxy}-1a-(2-oxo-1,3-dioxolan-4-yl)-2,3,8,9-tetradehydro-1a,5,6,9a-tetrahydrocyclopenta[5,6]cyclonona[1,2-b]oxiren-5-yl 2-hydroxy-7-methoxy-5-methyl-1-naphthoate
Identifiers
CAS number	[79633-18-4 [79633-18-4]] , Neocarzinostatin chromophore; [9014-02-2], Neocarzinostatin
ChemSpider	21106457
Jmol-3D images	Image 1
	SMILES COc7cc1c(ccc(O)c1C(=O)O[C@@H]3\C=C4\C#C[C@@]5(OC5C#CCC4[C@H]3O[C@H]2O[C@H](C)[C@H](O)[C@H](O)[C@H]2NC)C6COC(=O)O6)c(C)c7 ;
	InChI InChI=1S/C35H35NO12/c1-16-12-19(42-4)14-22-20(16)8-9-23(37)27(22)32(40)45-24-13-18-10-11-35(26-15-43-34(41)46-26)25(48-35)7-5-6-21(18)31(24)47-33-28(36-3)30(39)29(38)17(2)44-33/h8-9,12-14,17,21,24-26,28-31,33,36-39H,6,15H2,1-4H3/t17-,21?,24-,25?,26?,28-,29+,30-,31-,33-,35+/m1/s1 ; Key: BLXZMHNVKCEIJX-LTZUVELHSA-N InChI=1/C35H35NO12/c1-16-12-19(42-4)14-22-20(16)8-9-23(37)27(22)32(40)45-24-13-18-10-11-35(26-15-43-34(41)46-26)25(48-35)7-5-6-21(18)31(24)47-33-28(36-3)30(39)29(38)17(2)44-33/h8-9,12-14,17,21,24-26,28-31,33,36-39H,6,15H2,1-4H3/t17-,21?,24-,25?,26?,28-,29+,30-,31-,33-,35+/m1/s1; Key: BLXZMHNVKCEIJX-LTZUVELHBD ;
Properties
Molecular formula	C35H33NO12
Molar mass	659.64 g/mol
Pharmacology
Excretion	Renal
	Except where noted otherwise, data are given for materials in their standard state (at 25 °C (77 °F), 100 kPa)
	(verify) (what is: /?)
	Infobox references

　　[★]

英: neocarzinostatin, NCS
同: ジノスタチン zinostatin
商: ネオカルチノスタチン

抗悪性腫瘍薬

[1] Shoji Kobayashi, Makiko Hori, Guang Xing Wang, and Masahiro Hirama (2006). "Formal Total Synthesis of Neocarzinostatin Chromophore". J. Org. Chem. 71 (2): 636–644. doi:10.1021/jo052031o+S0022-3263(05)02031-1. PMID 16408974.

匿名

検索

案内

案内

neocarzinostatin