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7689-03-4 分子结构
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(19S)-19-ethyl-19-hydroxy-17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2,4,6,8,10,15(20)-heptaene-14,18-dione

ChemBase编号:4244
分子式:C20H16N2O4
平均质量:348.35204
单一同位素质量:348.111007
SMILES和InChIs

SMILES:
O=c1c2COC(=O)[C@](c2cc2n1Cc1cc3c(nc21)cccc3)(O)CC
Canonical SMILES:
CC[C@@]1(O)C(=O)OCc2c1cc1c3nc4ccccc4cc3Cn1c2=O
InChI:
InChI=1S/C20H16N2O4/c1-2-20(25)14-8-16-17-12(7-11-5-3-4-6-15(11)21-17)9-22(16)18(23)13(14)10-26-19(20)24/h3-8,25H,2,9-10H2,1H3/t20-/m0/s1
InChIKey:
VSJKWCGYPAHWDS-FQEVSTJZSA-N

引用这个纪录

CBID:4244 http://www.chembase.cn/molecule-4244.html

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名称和登记号

名称和登记号

名称 登记号
IUPAC标准名
(19S)-19-ethyl-19-hydroxy-17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2,4,6,8,10,15(20)-heptaene-14,18-dione
(19S)-19-ethyl-19-hydroxy-17-oxa-3,13-diazapentacyclo[11.8.0.0^{2,11}.0^{4,9}.0^{15,20}]henicosa-1(21),2(11),3,5,7,9,15(20)-heptaene-14,18-dione
(19S)-19-ethyl-19-hydroxy-17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2(11),3,5,7,9,15(20)-heptaene-14,18-dione
IUPAC传统名
camptothecin
(19S)-19-ethyl-19-hydroxy-17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2(11),3,5,7,9,15(20)-heptaene-14,18-dione
别名
(S)-4-Ethyl-4-hydroxy-1H-pyrano[3’,4’:6,7]indolizino[1,2-b]quinoline-3,14(4H,12H)-dione
(S)-(+)-Camptothecin
(4S)-4-Ethyl-4-hydroxy-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14(4H,12H)-dione
CPT
D-camptothecin
(+)-camptothecin
(+)-camptothecine
(s)-(+)-camptothecin
(s)-camptothecin
20(S)-Camptothecin
21,22-Secocamptothecin-21-oic acid lactone
Camptothecine
Camptothecin
(S)-(+)-Camptothecin
(S)-4-ethyl-4-hydroxy-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14(4H,12H)-dione
Camptothecin
CAS号
7689-03-4
MDL号
MFCD00081076
Beilstein号
631069
PubChem SID
160967676
46507644
PubChem CID
24360

理论计算性质

理论计算性质

JChem ALOGPS 2.1
Acid pKa 11.708908  质子受体
质子供体 LogD (pH = 5.5) 1.2186455 
LogD (pH = 7.4) 1.2202017  Log P 1.2202432 
摩尔折射率 94.4925 cm3 极化性 37.18863 Å3
极化表面积 79.73 Å2 可自由旋转的化学键
里宾斯基五规则 true 
Log P 1.91  LOG S -2.83 
溶解度 5.11e-01 g/l 

分子性质

分子性质

理化性质 安全信息 药理学性质 产品相关信息 生物活性(PubChem)
溶解度
Acetonitrile expand 查看数据来源
DMSO expand 查看数据来源
Methanol expand 查看数据来源
外观
Pale Yellow Solid expand 查看数据来源
Yellow powder expand 查看数据来源
熔点
239-245°C (dec.) expand 查看数据来源
260 °C (dec.)(lit.) expand 查看数据来源
260(dec.)°C expand 查看数据来源
疏水性(logP)
1.74 [HANSCH,C ET AL. (1995)] expand 查看数据来源
保存条件
-20°C expand 查看数据来源
-20°C Freezer expand 查看数据来源
保存注意事项
IRRITANT expand 查看数据来源
Toxic/Keep Cold expand 查看数据来源
RTECS编号
UQ0492000 expand 查看数据来源
欧盟危险性物质标志
有毒(Toxic) 有毒(Toxic) (T) expand 查看数据来源
联合国危险货物编号
1544 expand 查看数据来源
MSDS下载
下载链接 expand 查看数据来源
下载链接 expand 查看数据来源
下载链接 expand 查看数据来源
德国WGK号
3 expand 查看数据来源
联合国危险货物等级
6.1 expand 查看数据来源
联合国危险货物包装类别(PG)
3 expand 查看数据来源
危险公开号
25 expand 查看数据来源
安全公开号
45 expand 查看数据来源
TSCA收录
false expand 查看数据来源
GHS危险品标识
GHS06 expand 查看数据来源
GHS警示词
Danger expand 查看数据来源
GHS危险声明
H301 expand 查看数据来源
GHS警示性声明
P301 + P310 expand 查看数据来源
个人保护装置
Eyeshields, Faceshields, Gloves, type P2 (EN 143) respirator cartridges expand 查看数据来源
RID/ADR
UN 1544 6.1/PG 3 expand 查看数据来源
作用靶点
Topoisomerase expand 查看数据来源
生物活性机理
Inhibits the DNA enzyme topoisomerase expand 查看数据来源
纯度
≥90% (sum of enantiomers, HPLC) expand 查看数据来源
95+% expand 查看数据来源
97.5 expand 查看数据来源
成盐信息
Free Base expand 查看数据来源
质检报告
下载链接 expand 查看数据来源
生物来源
Alkaloid from Camptotheca acuminata, Mappia foetida, Ervatamia heyneana and Ophiorrhiza mungos (Nyssaceae, Rubiaceae, Apocynaceae) expand 查看数据来源
应用领域
Cytostatic expand 查看数据来源
Severe side effects and rapid hydrol. at physiological pH have inhibited widespread clinical use expand 查看数据来源
Shows anti-HIV and antiprotozoal activity expand 查看数据来源
Shows plant growth regulatory and insect chemosterilant props. expand 查看数据来源
Shows potent antineoplastic activity in exp. animals expand 查看数据来源
Used clinically in China against gastrointestinal tumours expand 查看数据来源
Empirical Formula (Hill Notation)
C20H16N2O4 expand 查看数据来源

详细说明

详细说明

DrugBank DrugBank Selleck Chemicals Selleck Chemicals Sigma Aldrich Sigma Aldrich TRC TRC
DrugBank -  DB04690 external link
Item Information
Drug Groups experimental
Description An alkaloid isolated from the stem wood of the Chinese tree, Camptotheca acuminata. This compound selectively inhibits the nuclear enzyme DNA topoisomerase, type I. Several semisynthetic analogs of camptothecin have demonstrated antitumor activity. [PubChem]
Indication Investigated for the treatment of cancer.
Pharmacology Camptothecin demonstrated strong anticancer activity in preliminary clinical trials but also low solubility and adverse drug reaction. Camptothecin is believed to be a potent topoisomerase inhibitor that interferes with the essential function of topoisomerase in DNA replication.
Toxicity Acute oral toxicity (LD50) in mouse: 50.1 mg/kg
Affected Organisms
Humans and other mammals
References
Wall ME, Wani MC: Camptothecin and taxol: from discovery to clinic. J Ethnopharmacol. 1996 Apr;51(1-3):239-53; discussion 253-4. [Pubmed]
Kepler JA, Wani MC, McNaull JN, Wall ME, Levine SG: Plant antitumor agents. IV. An approach toward the synthesis of camptothecin. J Org Chem. 1969 Dec;34(12):3853-8. [Pubmed]
External Links
Wikipedia
Selleck Chemicals -  S1288 external link
Research Area
Description Cancer
Biological Activity
Description Camptothecin (Camptohecine, 20-(S)-Camptothecin, CPT, NSC100880) is a specific inhibitor of DNA topoisomerase I (Topo I) with IC50 of 0.68 μM.
Targets DNA topoisomerase I (topo I)
IC50 0.68 μM [2]
In Vitro Camptothecin, a plant alkaloid orignially isolated from Camptotheca acuminate in 1966. [1] Camptothecin is noted to halt cells during the S phase of mitosis. Camptothecin displays nanomolar potency in cytotoxicity against many human tumor cell lines, including HT29, LOX, SKOV3, and SKVLB, with IC50 values ranging from 37 nM to 48 nM. [2]In combination with TNF, Camptothecin induces apoptosis in primary mouse hepatocytes, with an IC50 value of 13 μM. Camptothecin also abrogated the TNF-induced NF-κB Activation, as well as the expression of TNF-receptor associated factor 2 (TRAF2), X-linked inhibitor of apoptosis protein (X-IAP), and FLICE-inhibitory protein (FLIP). [4]In HCT116 cells, Camptothecin (5 μM) induces proteasome-mediated degradation of mixed lineage leukemia 5 (MLL5) protein, which leads to phosphorylation of p53 at Ser392. [5]Due to the low solubility and adverse effects of Camptothecin, various Camptothecin analogues have been developed, and two of them, topotecan and irinotecan, has been approved by FDA and are used in cancer chemotherapy.
In Vivo Camptothecin (8 mg/kg) displays complete growth inhibition and regression in mice xenografts of various tumors, including colon, lung, breast, stomach, and ovary tumors. [3]In mice, combinations of Camptothecin (50 mg/kg) and TNF (5 and 7 μg/kg), but not Camptothecin alone, induces liver damage. [4]
Clinical Trials Investigations of Camptothecin and its analogues in multiple Phase I–III clinical trials for various cancers have been completed.
Features
Protocol
Kinase Assay [2]
Topoisomerase I Cleavable Complex Assay Topoisomerase I is isolated from calf thymus and is devoid of topoisomerase II. All reactions are carried out in 10 mL volumes of reaction buffer (50 mM Tris-HCl, pH 7.5, 100 mM KCl, 0.5 mM EDTA, and 30 pg/mL BSA) in microtiter plates. Camptothecin is dissolved in DMSO at 10 mg/mL and serially diluted in 96-well microtiter plates to which the 32P end-labeled pBR322 DNA and topoisomerase enzyme are added. The reaction mixture is incubated at room temperature for 30 min and then the reaction stopped by adding 2 mL of a mixture of sodium dodecyl sulfate and proteinase K (1.6% and 0.14 mg/mL final concentrations, respectively). The plates are heated at 50 °C for 30 min, 10 mL of standard stop mixture containing 0.45 N NaOH is added in order to generate single-stranded DNA, and the samples are electrophoresed in 1.5% agarose gels in TBE buffer. Gels are blotted on nitrocellulose paper, dried, and exposed to X-ray film. The units of cleavage are calculated from the autoradiographs and plotted against the log drug concentration. The IC50 values are then obtained.
Cell Assay [2]
Cell Lines U87MG, A549 and H838 cells
Concentrations 0.17 nM–10 mM
Incubation Time 48 hours
Methods Tumor cells are plated in 100 μL of medium in 96-well microtiter plates at a density of 1500 to 4000 cells per well and allowed to adhere overnight. Cells are incubated with Camptothecin for 48 hours and then with fresh medium for 48 hours. Camptothecin at each concentration is added in quadruplicate. Following a 4-hour incubation of treated cells with MTT, the reduced dye product is extracted from the cells with 0.2 mL of DMSO followed by 50 μL of Sorensen's buffer. The plates are shaken briefly, and the absorbance at 570 nm is read and quantitated. Curves are fitted to the MTT assay data using a four-parameter logistic equation.
Animal Study [3]
Animal Models Nude mice (NIH-I high fertility strain) bearing xenografts of CASE, SW48, DOY, SPA, and CLO cells
Formulation Finely grounded and dispersed in intralipid 20% at 1 mg/mL by sonication
Doses 0–8 mg/kg
Administration Administered via i.m. or i.v. injection
References
[1] Wall ME, et al. J Am Chem Soc, 1966, 88 (16), 3888–3890.
[2] Luzzio MJ, et al. J Med Chem, 1995, 38(3), 395-401.
[3] Giovanella BC, et al. Cancer Res, 1991, 51(11), 3052-3055.
[4] Hentze H, et al. Hepatology, 2004, 39(5), 1311-1320.
[5] Cheng F, et al. Oncogene, 2011, 30(33), 3599-3611.
Sigma Aldrich -  21376 external link
Other Notes
Eukaryotic DNA topoisomerase I poison. Used to study the interaction of topo I with DNA1,2; DNA topoisomerases, review3
Toronto Research Chemicals -  C175150 external link
Antitumor alkaloid. Binds irreversible to the DNA-topoisomerase I complex, inhibiting the reassociation of DNA after cleavage by topoisomerase I and traps the enzyme in a covalent linkage with DNA. A cytotoxic antitumor agent.

参考文献

参考文献

供应商提供 Google Scholar IconGoogle Scholar PubMed iconPubMed Google Books IconGoogle Books
  • Wall ME, Wani MC: Camptothecin and taxol: from discovery to clinic. J Ethnopharmacol. 1996 Apr;51(1-3):239-53; discussion 253-4. Pubmed
  • Kepler JA, Wani MC, McNaull JN, Wall ME, Levine SG: Plant antitumor agents. IV. An approach toward the synthesis of camptothecin. J Org Chem. 1969 Dec;34(12):3853-8. Pubmed
  • Wall ME, et al. J Am Chem Soc, 1966, 88 (16), 3888–3890.
  • Luzzio MJ, et al. J Med Chem, 1995, 38(3), 395-401.
  • Giovanella BC, et al. Cancer Res, 1991, 51(11), 3052-3055.
  • Hentze H, et al. Hepatology, 2004, 39(5), 1311-1320.
  • Cheng F, et al. Oncogene, 2011, 30(33), 3599-3611.
  • Potmesil, M., et al.: Cancer Res., 54, 1431 (1994)
  • Desai, S.D., et al.: J. Biol. Chem., 272, 24159 (1994)
  • Fan, Y., et al.: J. Med. Chem., 41, 2216 (1994)
  • Kaufmann, S.H., et al.: Biochim. Biophys. Acta, 1400, 195 (1994)
  • Wall, M.E. et al., J.A.C.S., 1966, 88, 3888, (isol, uv, ir, pmr, cryst struct)
  • Winterfeldt, E. et al., Angew. Chem., Int. Ed., 1972, 11, 289, (synth)
  • Boch, M. et al., Chem. Ber., 1972, 105, 2126, (synth)
  • Tang, C. et al., J.A.C.S., 1972, 94, 8615, (synth, uv)
  • Sugasawa, T. et al., Chem. Pharm. Bull., 1974, 22, 77, (synth, ir, pmr)
  • Tang, C.S.F. et al., J.A.C.S., 1975, 97, 159, (synth, uv, pmr)
  • Bradley, J.C. et al., J.O.C., 1976, 41, 699, (synth)
  • Sheriha, G.M. et al., Phytochemistry, 1976, 15, 505, (biosynth)
  • Heckendorf, A.H. et al., Tet. Lett., 1977, 4153, (biosynth)
  • Martindale, The Extra Pharmacopoeia, 28th/29th edn., Pharmaceutical Press, 1982, 12515
  • Cai, J.-C. et al., Alkaloids (N.Y.), 1983, 21, 101, (rev, pharmacol)
  • Earl, R.A., J.A.C.S., 1983, 105, 6991, (synth)
  • Ihara, M. et al., J.O.C., 1983, 48, 3150, (synth)
  • Earl, R.A. et al., J.O.C., 1984, 49, 4786, (synth)
  • Suffness, M. et al., Alkaloids (N.Y.), 1985, 25, 83, (antineoplastic activity)
  • Priel, E., AIDS Res. Hum. Retroviruses, 1991, 7, 65, (anti-HIV activity)
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  • Comins, D.L. et al., J.A.C.S., 1992, 114, 10971, (synth)
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