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97682-44-5 分子结构
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(19S)-10,19-diethyl-19-hydroxy-14,18-dioxo-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)-heptaen-7-yl 4-(piperidin-1-yl)piperidine-1-carboxylate

ChemBase编号:642
分子式:C33H38N4O6
平均质量:586.67802
单一同位素质量:586.27913496
SMILES和InChIs

SMILES:
O(C(=O)N1CCC(N2CCCCC2)CC1)c1cc2c(c3Cn4c(c3nc2cc1)cc1[C@@](O)(CC)C(=O)OCc1c4=O)CC
Canonical SMILES:
CC[C@@]1(O)C(=O)OCc2c1cc1c3nc4ccc(cc4c(c3Cn1c2=O)CC)OC(=O)N1CCC(CC1)N1CCCCC1
InChI:
InChI=1S/C33H38N4O6/c1-3-22-23-16-21(43-32(40)36-14-10-20(11-15-36)35-12-6-5-7-13-35)8-9-27(23)34-29-24(22)18-37-28(29)17-26-25(30(37)38)19-42-31(39)33(26,41)4-2/h8-9,16-17,20,41H,3-7,10-15,18-19H2,1-2H3/t33-/m0/s1
InChIKey:
UWKQSNNFCGGAFS-XIFFEERXSA-N

引用这个纪录

CBID:642 http://www.chembase.cn/molecule-642.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)-10,19-diethyl-19-hydroxy-14,18-dioxo-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)-heptaen-7-yl 4-(piperidin-1-yl)piperidine-1-carboxylate
(19S)-10,19-diethyl-19-hydroxy-14,18-dioxo-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)-heptaen-7-yl 4-(piperidin-1-yl)piperidine-1-carboxylate
IUPAC传统名
irinotecan
(19S)-10,19-diethyl-19-hydroxy-14,18-dioxo-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)-heptaen-7-yl 4-(piperidin-1-yl)piperidine-1-carboxylate
商标名
CP0
Camptosar
IRINOTECAN, CPT-11
别名
Irinotecan Hydrochloride
Irinotecan Hydrochloride Trihydrate
Irinotecan Hcl
Irinotecanum [INN-Latin]
irinotecan
Irinotecan
Camptosar
Camptetin
Campto
Topotecin
Irinotecan
CAS号
97682-44-5
100286-90-6
PubChem SID
46505871
160964105
PubChem CID
60838

数据来源

数据来源

所有数据来源 商品来源 非商品来源

理论计算性质

理论计算性质

JChem ALOGPS 2.1
Acid pKa 11.713039  质子受体
质子供体 LogD (pH = 5.5) -0.6070732 
LogD (pH = 7.4) 0.7157881  Log P 2.776473 
摩尔折射率 161.3303 cm3 极化性 63.005684 Å3
极化表面积 112.51 Å2 可自由旋转的化学键
里宾斯基五规则 false 
Log P 3.94  LOG S -3.74 
溶解度 1.07e-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
DMSO expand 查看数据来源
Soluble expand 查看数据来源
疏水性(logP)
3.2 expand 查看数据来源
保存条件
-20°C 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
Topoisomerase I inhibitor expand 查看数据来源
成盐信息
Free Base expand 查看数据来源
应用领域
Antineoplastic agent expand 查看数据来源
Use is in colon cancer expand 查看数据来源

详细说明

详细说明

DrugBank DrugBank Selleck Chemicals Selleck Chemicals
DrugBank -  DB00762 external link
Item Information
Drug Groups approved; investigational
Description Irinotecan is an antineoplastic enzyme inhibitor primarily used in the treatment of colorectal cancer. It is a derivative of camptothecin that inhibits the action of topoisomerase I. Irinotecan prevents religation of the DNA strand by binding to topoisomerase I-DNA complex, and causes double-strand DNA breakage and cell death.
Indication For the treatment of metastatic colorectal cancer (first-line therapy when administered with 5-fluorouracil and leucovorin). Also used in combination with cisplatin for the treatment of extensive small cell lung cancer. Irinotecan is currently under investigation for the treatment of metastatic or recurrent cervical cancer.
Pharmacology Irinotecan is an antineoplastic enzyme inhibitor primarily used in the treatment of colorectal cancer. Irinotecan is a semisynthetic derivative of camptothecin. Camptothecins interact specifically with topoisomerase I, an enzyme in the cell nucleus that regulates DNA topology and facilitates nuclear processes such as DNA replication, recombination, and repair. During these processes, topoisomerase I relieves torsional strain in DNA by inducing reversible single-strand breaks, allowing single DNA strands to pass through the break. The 3'-DNA terminus of the broken DNA strands bind covalently with the topoisomerase enzyme to form a catalytic intermediate called a cleavable complex. After the DNA is sufficiently relaxed and the strand passage reaction is complete, DNA topoisomerase reattaches the broken DNA strands to form the chemically unaltered topoisomers that allow transcription to proceed. Irinotecan and its active metabolite SN-38 bind to the topoisomerase I-DNA complex and prevent religation of these single-strand breaks. Current research suggests that the cytotoxicity of irinotecan is due to double-strand DNA damage produced during DNA synthesis when replication enzymes interact with the ternary complex formed by topoisomerase I, DNA, and either Irinotecan or SN-38. Mammalian cells cannot efficiently repair these double-strand breaks. The precise contribution of SN-38 to the activity of irinotecan in humans is not known. Irinotecan is cell cycle phase-specific (S-phase).
Toxicity Gastrointestinal complications, such as nausea, vomiting, abdominal cramping, diarrhea, and infection.
Affected Organisms
Humans and other mammals
Biotransformation Hepatic
Absorption 100%
Half Life 6-12 hours
Protein Binding 30%-68%
Elimination The cumulative biliary and urinary excretion of irinotecan and its metabolites (SN-38 and SN-38 glucuronide) over a period of 48 hours following administration of irinotecan in two patients ranged from approximately 25% (100 mg/m2) to 50% (300 mg/m2).
References
Innocenti F, Undevia SD, Iyer L, Chen PX, Das S, Kocherginsky M, Karrison T, Janisch L, Ramirez J, Rudin CM, Vokes EE, Ratain MJ: Genetic variants in the UDP-glucuronosyltransferase 1A1 gene predict the risk of severe neutropenia of irinotecan. J Clin Oncol. 2004 Apr 15;22(8):1382-8. Epub 2004 Mar 8. [Pubmed]
O'Dwyer PJ, Catalano RB: Uridine diphosphate glucuronosyltransferase (UGT) 1A1 and irinotecan: practical pharmacogenomics arrives in cancer therapy. J Clin Oncol. 2006 Oct 1;24(28):4534-8. [Pubmed]
Ramesh M, Ahlawat P, Srinivas NR: Irinotecan and its active metabolite, SN-38: review of bioanalytical methods and recent update from clinical pharmacology perspectives. Biomed Chromatogr. 2010 Jan;24(1):104-23. [Pubmed]
Chabot GG: Clinical pharmacokinetics of irinotecan. Clin Pharmacokinet. 1997 Oct;33(4):245-59. [Pubmed]
External Links
Wikipedia
RxList
Drugs.com
Selleck Chemicals -  S1198 external link
Research Area
Description Solid tumours
Biological Activity
Description Irinotecan (Camptosar, Campto, CPT-11) is a topoisomerase I inhibitor for LoVo cells and HT-29 cells with IC50 of 15.8 μM and 5.17 μM, respectively.
Targets LoVo cells HT-29 cells
IC50 15.8 μM 5.17 μM [1]
In Vitro Irinotecan is activated to SN-38 by carboxylesterases to become able to interact with its target, topoisomerase I. Irinotecan induces similar amounts of cleavable complexes at its IC50 in LoVo cells and HT-29 cell lines. SN-38 induces a concentration-dependent formation of cleavable complexes, which is not significantly different in LoVo cells and HT-29 cell lines. Cell accumulation of Irinotecan is markedly different, reaching consistently higher levels in HT-29 cells than in LoVo cells. [1] The lactone E-ring of Irinotecan and SN-38 hydrolyses reversibly in aqueous solutions, and the interconversion between the lactone and carboxylate forms is dependent on pH and temperature. Liver is primarily responsible for the activation of Irinotecan to SN-38. At equal concentrations of Irinotecan and SN-38 glucuronide, the rate of beta-glucuronidase-mediated SN-38 production is higher than that formed from Irinotecan in both tumour and normal tissue. [2] Irinotecan is also converted to SN-38 in intestines, plasma and tumor tissues. [3] Irinotecan is significantly more active in SCLC than in NSCLC cell lines, whereas no significant difference between histological types is observed with SN-38. [4]
In Vivo In COLO 320 xenografts, Irinotecan induces a maximum growth inhibition of 92%. [5] A single dose of Irinotecan significantly increases amounts of topoisomerase I covalently bound to DNA in stomach, duodenum, colon and liver. Concomitantly, the Irinotecan-treated group shows significantly higher amounts of DNA strand breaks in colon mucosa cells compared to the control group. [6]
Clinical Trials Irinotecan has entered in a phase II clinical trial in the treatment of non-small cell lung cancer.
Features Irinotecan is a prodrug that is used to treat metastatic colorectal cancer.
Protocol
Cell Assay [1]
Cell Lines LoVo and HT-29 cells
Concentrations 0 μM -100 μM
Incubation Time 48 hours
Methods Exponentially growing cells (LoVo and HT-29 cells) are seeded in 20 cm2 Petri dishes with an optimal cell number for each cell line (2 × 104 for LoVo cells, 105 for HT-29 cells). They are treated 2 days later with increasing concentrations of Irinotecan or SN-38 for one cell doubling time (24 hours for LoVo cells, 40 hours for HT-29 cells). After washing with 0.15 M NaCl, the cells are further grown for two doubling times in normal medium, detached from the support with trypsin-EDTA and counted in a hemocytometer. The IC50 values are then estimated as the Irinotecan or SN-38 concentrations responsible for 50% growth inhibition as compared with cells incubated without Irinotecan or SN-38.
Animal Study [5]
Animal Models Female nude mice with COLO 320 and WiDr xenografts
Formulation 0.9% NaCl
Doses 20 mg/kg
Administration Administered via i.p.
References
[1] Pavillard V, et al. Cancer Chemother Pharmacol. 2002, 49(4), 329-335.
[2] Tobin P, et al. Br J Clin Pharmacol. 2006, 62(1), 122-129.
[3] Shingyoji M, et al. Cancer Sci. 2004, 95(6), 537-540.
[4] van Ark-Otte J, et al. Br J Cancer. 1998, 77(12), 2171-2176.
[5] Jansen WJ, et al. Int J Cancer. 1997, 70(3):335-340.
[6] Na YS, et al. Cancer Chemother Pharmacol. 2011, 68(2), 389-398.
[7] Wagner LM, et al. Pediatr Blood Cancer. 2007, 48(2), 132-139.

参考文献

参考文献

供应商提供 Google Scholar IconGoogle Scholar PubMed iconPubMed Google Books IconGoogle Books
  • Chabot GG: Clinical pharmacokinetics of irinotecan. Clin Pharmacokinet. 1997 Oct;33(4):245-59. Pubmed
  • Innocenti F, Undevia SD, Iyer L, Chen PX, Das S, Kocherginsky M, Karrison T, Janisch L, Ramirez J, Rudin CM, Vokes EE, Ratain MJ: Genetic variants in the UDP-glucuronosyltransferase 1A1 gene predict the risk of severe neutropenia of irinotecan. J Clin Oncol. 2004 Apr 15;22(8):1382-8. Epub 2004 Mar 8. Pubmed
  • O'Dwyer PJ, Catalano RB: Uridine diphosphate glucuronosyltransferase (UGT) 1A1 and irinotecan: practical pharmacogenomics arrives in cancer therapy. J Clin Oncol. 2006 Oct 1;24(28):4534-8. Pubmed
  • Ramesh M, Ahlawat P, Srinivas NR: Irinotecan and its active metabolite, SN-38: review of bioanalytical methods and recent update from clinical pharmacology perspectives. Biomed Chromatogr. 2010 Jan;24(1):104-23. Pubmed
  • Pavillard V, et al. Cancer Chemother Pharmacol. 2002, 49(4), 329-335.
  • Tobin P, et al. Br J Clin Pharmacol. 2006, 62(1), 122-129.
  • Shingyoji M, et al. Cancer Sci. 2004, 95(6), 537-540.
  • van Ark-Otte J, et al. Br J Cancer. 1998, 77(12), 2171-2176.
  • Jansen WJ, et al. Int J Cancer. 1997, 70(3):335-340.
  • Na YS, et al. Cancer Chemother Pharmacol. 2011, 68(2), 389-398.
  • Wagner LM, et al. Pediatr Blood Cancer. 2007, 48(2), 132-139.
  • Boisseau, M. et al., Expert Opin. Invest. Drugs, 1996, 5, 613, (rev)
  • Henegar, K.E. et al., J.O.C., 1997, 62, 6588-6597, (synth)
  • Robert, J. et al., Drugs of Today (Barcelona), 1998, 34, 777-803, (rev)
  • Martindale, The Extra Pharmacopoeia, 32nd edn., Pharmaceutical Press, 1999, 543
  • Nitta, K. et al., Recent Adv. Chemother., Proc. Int. Congr. Chemother., 14th, 1985, 1, 28, (synth, pharmacol)
  • Kunimoto, T. et al., Cancer Res., 1987, 47, 5944, (pharmacol)
  • Koike, K. et al., Gen. Pharmacol., 1989, 20, 763, (pharmacol)
  • Kaneda, N. et al., Cancer Res., 1990, 50, 1715, (metab)
  • Sawada, S. et al., Chem. Pharm. Bull., 1991, 39, 1446, (synth, trihydrate, pmr, uv, cmr, cryst struct, activity)
  • Atsumi, R. et al., Xenobiotica, 1991, 21, 1159, (metab)
  • Aiyama, R. et al., Chem. Pharm. Bull., 1992, 40, 2810, (uv, cd, bibl)
  • Burris, H.A. et al., Semin. Oncol., 1992, 19, 663, (use, rev)
  • Rivory, L.P. et al., Cancer Res., 1994, 54, 6330, (metab, human)
  • Curran, D.P. et al., Angew. Chem., Int. Ed., 1995, 34, 2683, (synth)
  • Wiseman, L.R. et al., Drugs, 1996, 52, 606, (rev)
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