Page last updated: 2024-12-10

zinostatin

Description Research Excerpts Clinical Trials Roles Classes Pathways Study Profile Bioassays Related Drugs Related Conditions Protein Interactions Research Growth Market Indicators

Description

Zinostatin: An enediyne that alkylates DNA and RNA like MITOMYCIN does, so it is cytotoxic. [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID5282473
SCHEMBL ID1347615
MeSH IDM0014562

Synonyms (8)

Synonym
zinostatin
9014-02-2
neocarzinostatin
zinostatin (usan/inn)
neocarzinostatin (jan)
D02046
SCHEMBL1347615
[(4s,6r,11r,12r)-11-[(2r,3r,4r,5r,6r)-4,5-dihydroxy-6-methyl-3-(methylamino)oxan-2-yl]oxy-4-[(4r)-2-oxo-1,3-dioxolan-4-yl]-5-oxatricyclo[8.3.0.04,6]tridec-1(13)-en-2,7-diyn-12-yl] 2-hydroxy-7-methoxy-5-methylnaphthalene-1-carboxylate

Research Excerpts

Treatment

ExcerptReferenceRelevance
"Treating neocarzinostatin samples with the cell extract that retained active sulfhydryls led to efficient drug inactivation, which indicates that mycothiol is allowed to approach the protein-bound chromophore."( Thiols screened by the neocarzinostatin protein for preserving or detoxifying its bound enediyne antibiotic.
Chi, HW; Chin, DH; Huang, CC, 2012
)
1.01

Toxicity

The toxic effect and antitumor activity of neocarzinostatin (NCS) and SMANCS [copoly(styrenemaleic acid)-conjugated NCS] were greatly affected by N-(2-mercaptopropionyl)-glycine [tiopronin] in cultured HeLa cells and RL male 1 tumor-bearing mice. The LD50 values of the conjugate and neocarcinostatin alone in the presence of excess native bovine transferrin were 0.

ExcerptReferenceRelevance
" In a solid tumor model, pyran-NCS and NCS suppressed tumor growth at three-fourths of the LD50 to 12."( Reduced bone marrow toxicity of neocarzinostatin by conjugation with divinyl ether-maleic acid copolymer.
Akagi, M; Hirano, T; Maeda, H; Miki, T; Oda, T; Sera, Y; Yamamoto, H, 1990
)
0.55
"The toxic effect and antitumor activity of neocarzinostatin (NCS) and SMANCS [copoly(styrenemaleic acid)-conjugated NCS] were greatly affected by N-(2-mercaptopropionyl)-glycine [tiopronin] both in vitro and in vivo, in cultured HeLa cells and RL male 1 tumor-bearing mice."( Differential neutralizing effect of tiopronin on the toxicity of neocarzinostatin and SMANCS: a new rescue cancer chemotherapy.
Maeda, H; Miki, T; Oda, T; Yamamoto, H, 1989
)
0.76
" Comparing the inhibition dose for 50% uptake (ID50) it was found that the monoclonal antibody-drug complex is about 100 times more toxic for the antigen-bearing cell line than free NCS or normal mouse IgG1-NCS."( Selective toxicity of neocarzinostatin-monoclonal antibody conjugates to the antigen-bearing human melanoma cell line in vitro.
Brüggen, J; Köhnlein, W; Lüders, G; Sorg, C, 1985
)
0.56
" To prevent these adverse side effects without changing the anticancer activity of the drug, we attempted to apply the two-route-infusion chemotherapy using NCS and antidotes for the NCS treatment devised by Baba."( [Screening for antagonistic agents to the lethal toxicity of neocarzinostatin. II. Effects of various drugs in inhibiting the toxicity of neocarzinostatin in vivo].
Baba, T; Matsumoto, T; Ouchi, M; Toriyama, K, 1988
)
0.51
" Experiments with AA8 cells in culture demonstrated that the enediyne antibiotics neocarzinostatin and esperamicin A, (ESP) are much less toxic under hypoxic than aerobic conditions."( Oxygen dependence of the cytotoxicity of the enediyne anti-tumour antibiotic esperamicin A1.
Batchelder, RM; Denny, WA; Hay, MP; Wilson, WR, 1996
)
0.52

Pharmacokinetics

ExcerptReferenceRelevance
" The pharmacokinetic properties of the combinations were subsequently examined."( Comparative pharmacokinetic properties of murine monoclonal antibody A7 modified with neocarzinostatin, dextran and polyethylene glycol.
Kitamura, K; Noguchi, A; Takahashi, T; Takashina, K; Tsurumi, H; Yamaguchi, T, 1991
)
0.5
" The conjugate was removed from the blood circulation with a half-life of 12 hr, showing nearly the same kinetics as the free antibody."( Pharmacokinetic analysis of the monoclonal antibody A7-neocarzinostatin conjugate administered to nude mice.
Kitamura, K; Noguchi, A; Okuzumi, J; Takahashi, T; Takashina, K; Tsurumi, H; Yamaguchi, T, 1991
)
0.52
"1 microgram/ml, despite the fact that the half-life of NCS is extremely short (3 seconds in serum)."( [Pharmacokinetics of neocarzinostatin in patients with malignant glioma. Quantitative analysis of tissue concentration].
Goto, S; Kuratsu, J; Matsukado, Y; Mihara, Y; Otsuka, T; Sonoda, H; Uemura, S, 1989
)
0.57
" Pharmacokinetic study was performed in order to establish intermittent intrathecal perfusion therapy and to prevent subarachnoid dissemination of the brain tumor cells."( [Pharmacokinetic one-compartment model using neocarzinostain as a prototype drug and its clinical application to chemotherapy for brain tumor. Part II. A clinical trial with selected protocol].
Kuratsu, J; Maeda, H; Matsukado, Y; Sonoda, H; Uemura, S, 1982
)
0.26
"A pharmacokinetic two-compartment model for the treatment of brain tumors in man was simulated with the aid of a computer."( A pharmacokinetic simulation model for chemotherapy of brain tumor with an antitumor protein antibiotic, neocarzinostatin. Theoretical considerations behind a two-compartment model for continuous infusion via an internal carotid artery.
Iwai, Z; Kosaka, H; Maeda, H; Marubayashi, T; Matsukado, Y; Sano, Y; Takeshita, J, 1981
)
0.47

Compound-Compound Interactions

Human fibroblast interferon (IFN)-beta was administered in combination with the free radical-generating antiproliferative agents bleomycin (BLM), neocarzinostatin (NCS) and mitomycin C (MMC) to HeLa cells in culture.

ExcerptReferenceRelevance
"The clinical effect and safety of Lp-TAE alone and combined with radiofrequency (RF) capacitive hyperthermia (HT) were evaluated in 20 patients with hepatocellular carcinoma (HCC) associated with cirrhosis of the liver."( Trans-catheter hepatic arterial injection of lipiodol soluble anti-cancer agent SMANCS and ADR suspension in lipiodol combined with arterial embolization and local hyperthermia for treatment of hepatocellular carcinoma.
Hara, K; Inatsuki, S; Jinno, K; Kobashi, H; Moriwaki, S; Okamoto, T; Toki, H; Tokuyama, K; Wada, T; Yumoto, Y,
)
0.13
" When a case of such was found inoperable, she was subjected to radiotherapy combined with aclarubicin and neocarzinostatin."( [Radiotherapy combined with aclarubicin and neocarzinostatin in cancer of the gallbladder].
Funaki, K; Mishina, H; Mori, T; Okuyama, S, 1991
)
0.75
"Human fibroblast interferon (IFN)-beta was administered in combination with the free radical-generating antiproliferative agents bleomycin (BLM), neocarzinostatin (NCS), adriamycin (ADM), and mitomycin C (MMC) to HeLa cells in culture."( Synergistic antiproliferative effect of interferon-beta in combination with bleomycin or neocarzinostatin on HeLa cells in culture: additive effect when combined with adriamycin or mitomycin C.
Hayashi, Y; Ito, M; Kawade, Y; Shigeta, S; Tanabe, F, 1987
)
0.69
" Protons on ethidium show NOE interactions to the following protein residues: Trp-39, Leu-45, Cys-47, and Gln-94 which interact with the phenanthridine ring system of ethidium, Gly-102 and Asn-103 which interact with the alkyl chain of ethidium, and Phe-52 which interacts with the phenyl ring of ethidium."( Sequential 1H NMR assignment of the complex of aponeocarzinostatin with ethidium bromide and investigation of protein-drug interactions in the chromophore binding site.
Drobny, GP; Mohanty, S; Sieker, LC, 1994
)
0.53
"0 cm) in main tumor diameter were treated by SMANCS-TAE (20 cases) or SMANCS-TAI (4 cases) combined with PEI."( [SMANCS-TAE combined with PEI in the treatment for hepatocellular carcinoma].
Arata, S; Fujii, T; Hori, A; Isozaki, T; Kiba, T; Kitamura, T; Kondo, M; Morimoto, M; Morita, K; Numata, K; Okazaki, H; Saito, S; Sekihara, H; Shimamura, T; Shirato, K; Tanaka, K, 1998
)
0.3

Dosage Studied

ExcerptRelevanceReference
"" The dose-response curves from BLM and NCS have identical slopes; they are characteristic for compounds which selectively inhibit DNA synthesis."( Additive effects of bleomycin and neocarzinostatin on degradation of DNA, inhibition of DNA polymerase beta, and cell growth.
Arendes, J; Geurtsen, W; Maidhof, A; Müller, WE; Schmidseder, R; Zahn, RK, 1979
)
0.53
" Metastatic lung cancer was declining in the initial dosage and 23 months later disappeared after the third dosage."( [A case of massive hepatoma which responded to SMANCS/Lipiodol regimen with intra-arterial infusion].
Fuchigami, T; Konno, T; Kubo, M; Maeda, H; Murata, S, 1989
)
0.28
" The advantages of this therapy include: (1) selective deposition of Lipiodol with the anti-cancer drug in the target tumor, (2) a pronounced and long-lasting anti-cancer effect, (3) enhanced visualization of the tumor on x-ray examinations for a prolonged period which also facilitated the long-term follow-up, (4) semiquantitative evaluation of the dosage regimen by x-ray examination before further administration, (5) general applicability due to procedural simplicity, and (6) little side effect."( Selective targeting of anti-cancer drug and simultaneous image enhancement in solid tumors by arterially administered lipid contrast medium.
Iwai, K; Konno, T; Maeda, H; Maki, S; Miyauchi, Y; Tashiro, S; Uchida, M, 1984
)
0.27
" The dose-response curve for NCS-induced damage suggested a two-hit-type event in the formation of chromosome breaks."( Induction and repair of DNA and chromosome damage by neocarzinostatin in quiescent normal human fibroblasts.
Hittelman, WN; Pollard, M, 1982
)
0.51
" Dosage reductions of 50% are recommended for patients with impaired renal function, while no reduction or escalated doses could be tolerated by patients with liver disease."( Clinical pharmacology of the anticancer polypeptide neocarzinostatin.
Benjamin, RS; Broughton, A; Hall, SW; Knight, J; McKelvey, E, 1983
)
0.51
" Differential diagnosis of primary or metastatic cancer became possible and dosing regimen can be determined since a presence of the contrast medium is restricted to the tumor area and it parallels to that of the drug being dissolved."( [Tumor selective drug delivery with lipid contrast medium (smancs/lipiodol): sustained antitumor effect, enhanced diagnostic value and quantification of dosage regimen].
Iwai, K; Konno, T; Maeda, H; Maki, S; Tashiro, S, 1984
)
0.27
", CT-scan), and thus the optimal dosing regimen can be determined and offers a diagnostic advantage."( [SMANCS/lipiodol].
Maeda, H, 1994
)
0.29
" First arterial administration of SMANCS was performed on May in 1994, followed by 6 successive procedures with an interval of about 2 months (total dosage 36 mg), resulting in remarkable tumor shrinkage and tumor marker normalization."( [A case of giant hepatocellular carcinoma successfully treated by arterial administration of SMANCS].
Ishii, K; Kinoshita, T; Miyasato, S; Miyazaki, A; Ohira, S; Sakurada, H; Shibuya, D; Tomiya, Y; Yajima, Y, 1996
)
0.29
" Thus the present system has the potential to reduce the dosage of anti-cancer drugs needed, and this strategy seems likely to be a valuable clinical tool in targeting immunotherapy."( Targeting immunotherapy using the avidin-biotin system for a human colon adenocarcinoma in vitro.
Nakaki, M; Takikawa, H; Yamanaka, M,
)
0.13
" Thus, an increase of infusion dosage or repeated infusions were recommended for such cases."( [Arterial infusion chemotherapy with SMANCS-Lipiodol for multiple hepatocellular carcinoma].
Doai, K; Hasebe, S; Honda, M; Kuniyasu, Y; Matsuoka, S; Obuchi, M; Satoh, S; Shima, H; Takizawa, K; Uchiyama, K, 1998
)
0.3
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (822)

TimeframeStudies, This Drug (%)All Drugs %
pre-1990394 (47.93)18.7374
1990's252 (30.66)18.2507
2000's115 (13.99)29.6817
2010's52 (6.33)24.3611
2020's9 (1.09)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 19.06

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be moderate demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index19.06 (24.57)
Research Supply Index6.78 (2.92)
Research Growth Index4.20 (4.65)
Search Engine Demand Index23.28 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (19.06)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials27 (3.18%)5.53%
Reviews58 (6.83%)6.00%
Case Studies50 (5.89%)4.05%
Observational0 (0.00%)0.25%
Other714 (84.10%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]