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Identification
- Generic Name
- Camptothecin
- DrugBank Accession Number
- DB04690
- Background
Camptothecin is 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.
- Type
- Small Molecule
- Groups
- Experimental
- Structure
Structure for Camptothecin (DB04690)
- Weight
- Average: 348.352
Monoisotopic: 348.11100701 - Chemical Formula
- C20H16N2O4
- Synonyms
- (+)-camptothecin
- (+)-camptothecine
- (S)-(+)-camptothecin
- 20(S)-camptothecine
- 21,22-Secocamptothecin-21-oic acid lactone
- Camptothecine
- D-camptothecin
Pharmacology
- Indication
Investigated for the treatment of cancer.
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Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
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.
- Mechanism of action
Camptothecin binds to the topoisomerase I and DNA complex resulting in a ternary complex, stabilizing it and preventing DNA re-ligation and therefore causes DNA damage which results in apoptosis.
Target Actions Organism UDNA topoisomerase 1 inhibitorHumans - Absorption
Not Available
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
- Not Available
- Route of elimination
Not Available
- Half-life
Not Available
- Clearance
Not Available
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
Acute oral toxicity (LD50) in mouse: 50.1 mg/kg
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbemaciclib Abemaciclib may decrease the excretion rate of Camptothecin which could result in a higher serum level. Afatinib Afatinib may decrease the excretion rate of Camptothecin which could result in a higher serum level. Alectinib Alectinib may decrease the excretion rate of Camptothecin which could result in a higher serum level. Ambroxol The risk or severity of methemoglobinemia can be increased when Camptothecin is combined with Ambroxol. Apalutamide The serum concentration of Camptothecin can be decreased when it is combined with Apalutamide. - Food Interactions
- Not Available
Categories
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as camptothecins. These are heterocyclic compounds comprising a planar pentacyclic ring structure, that includes a pyrrolo[3,4-beta]-quinoline moiety (rings A, B and C), conjugated pyridone moiety (ring D) and one chiral center at position 20 within the alpha-hydroxy lactone ring with (S) configuration (the E-ring).
- Kingdom
- Organic compounds
- Super Class
- Alkaloids and derivatives
- Class
- Camptothecins
- Sub Class
- Not Available
- Direct Parent
- Camptothecins
- Alternative Parents
- Quinolines and derivatives / Pyranopyridines / Pyridinones / Benzenoids / Tertiary alcohols / Heteroaromatic compounds / Carboxylic acid esters / Lactams / Lactones / Azacyclic compounds show 7 more
- Substituents
- Alcohol / Aromatic heteropolycyclic compound / Azacycle / Benzenoid / Camptothecin / Carbonyl group / Carboxylic acid derivative / Carboxylic acid ester / Heteroaromatic compound / Hydrocarbon derivative show 16 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- quinoline alkaloid, pyranoindolizinoquinoline (CHEBI:27656) / Alkaloids, Quinoline alkaloids (C01897)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- XT3Z54Z28A
- CAS number
- 7689-03-4
- InChI Key
- VSJKWCGYPAHWDS-FQEVSTJZSA-N
- 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
- IUPAC Name
- (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),2,4,6,8,10,15(20)-heptaene-14,18-dione
- SMILES
- CC[C@@]1(O)C(=O)OCC2=C1C=C1N(CC3=CC4=CC=CC=C4N=C13)C2=O
References
- Synthesis Reference
Tadashi Miyasaka, Seigo Sawada, Kenichiro Nokata, Masahiko Mutai, "Photochemical process for preparing camptothecin derivatives." U.S. Patent US4545880, issued March, 1976.
US4545880- General References
- Wall ME, Wani MC: Camptothecin and taxol: from discovery to clinic. J Ethnopharmacol. 1996 Apr;51(1-3):239-53; discussion 253-4. [Article]
- 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. [Article]
- External Links
- KEGG Compound
- C01897
- PubChem Compound
- 24360
- PubChem Substance
- 46507644
- ChemSpider
- 22775
- BindingDB
- 50008923
- ChEBI
- 27656
- ChEMBL
- CHEMBL65
- ZINC
- ZINC000000105309
- PharmGKB
- PA153590860
- PDBe Ligand
- EHD
- Wikipedia
- Camptothecin
- PDB Entries
- 1t8i
- MSDS
- Download (73.9 KB)
Clinical Trials
- Clinical Trials
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Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
- Not Available
- Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 275-277 °C Volkmann logP 1.74 HANSCH,C ET AL. (1995) - Predicted Properties
Property Value Source Water Solubility 0.511 mg/mL ALOGPS logP 1.91 ALOGPS logP 1.22 Chemaxon logS -2.8 ALOGPS pKa (Strongest Acidic) 11.71 Chemaxon pKa (Strongest Basic) 3.07 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 4 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 79.73 Å2 Chemaxon Rotatable Bond Count 1 Chemaxon Refractivity 94.49 m3·mol-1 Chemaxon Polarizability 36.4 Å3 Chemaxon Number of Rings 5 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.841 Blood Brain Barrier - 0.6345 Caco-2 permeable - 0.5555 P-glycoprotein substrate Substrate 0.6039 P-glycoprotein inhibitor I Non-inhibitor 0.7852 P-glycoprotein inhibitor II Non-inhibitor 0.9762 Renal organic cation transporter Non-inhibitor 0.8376 CYP450 2C9 substrate Non-substrate 0.8311 CYP450 2D6 substrate Non-substrate 0.8454 CYP450 3A4 substrate Substrate 0.546 CYP450 1A2 substrate Inhibitor 0.9106 CYP450 2C9 inhibitor Non-inhibitor 0.907 CYP450 2D6 inhibitor Non-inhibitor 0.9232 CYP450 2C19 inhibitor Non-inhibitor 0.9025 CYP450 3A4 inhibitor Inhibitor 0.7959 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.5591 Ames test Non AMES toxic 0.5393 Carcinogenicity Non-carcinogens 0.8187 Biodegradation Not ready biodegradable 1.0 Rat acute toxicity 3.3261 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9939 hERG inhibition (predictor II) Non-inhibitor 0.902
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 195.4489731 predictedDarkChem Lite v0.1.0 [M-H]- 195.6352731 predictedDarkChem Lite v0.1.0 [M-H]- 177.12344 predictedDeepCCS 1.0 (2019) [M+H]+ 196.3229731 predictedDarkChem Lite v0.1.0 [M+H]+ 195.9605731 predictedDarkChem Lite v0.1.0 [M+H]+ 179.48145 predictedDeepCCS 1.0 (2019) [M+Na]+ 196.2859731 predictedDarkChem Lite v0.1.0 [M+Na]+ 195.7564731 predictedDarkChem Lite v0.1.0 [M+Na]+ 186.02837 predictedDeepCCS 1.0 (2019)
Targets
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Releases the supercoiling and torsional tension of DNA introduced during the DNA replication and transcription by transiently cleaving and rejoining one strand of the DNA duplex. Introduces a single-strand break via transesterification at a target site in duplex DNA. The scissile phosphodiester is attacked by the catalytic tyrosine of the enzyme, resulting in the formation of a DNA-(3'-phosphotyrosyl)-enzyme intermediate and the expulsion of a 5'-OH DNA strand. The free DNA strand then rotates around the intact phosphodiester bond on the opposing strand, thus removing DNA supercoils. Finally, in the religation step, the DNA 5'-OH attacks the covalent intermediate to expel the active-site tyrosine and restore the DNA phosphodiester backbone (By similarity). Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells. Involved in the circadian transcription of the core circadian clock component BMAL1 by altering the chromatin structure around the ROR response elements (ROREs) on the BMAL1 promoter
- Specific Function
- Atp binding
- Gene Name
- TOP1
- Uniprot ID
- P11387
- Uniprot Name
- DNA topoisomerase 1
- Molecular Weight
- 90725.19 Da
References
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
- Teicher BA: Next generation topoisomerase I inhibitors: Rationale and biomarker strategies. Biochem Pharmacol. 2008 Mar 15;75(6):1262-71. Epub 2007 Oct 22. [Article]
- van der Merwe M, Bjornsti MA: Mutation of Gly721 alters DNA topoisomerase I active site architecture and sensitivity to camptothecin. J Biol Chem. 2008 Feb 8;283(6):3305-15. Epub 2007 Dec 4. [Article]
- Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [Article]
- Mattern MR, Mong S, Mong SM, Bartus JO, Sarau HM, Clark MA, Foley JJ, Crooke ST: Transient activation of topoisomerase I in leukotriene D4 signal transduction in human cells. Biochem J. 1990 Jan 1;265(1):101-7. doi: 10.1042/bj2650101. [Article]
Carriers
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transporter in plasma, typically binds about 80% of all plasma zinc (PubMed:19021548). Major calcium and magnesium transporter in plasma, binds approximately 45% of circulating calcium and magnesium in plasma (By similarity). Potentially has more than two calcium-binding sites and might additionally bind calcium in a non-specific manner (By similarity). The shared binding site between zinc and calcium at residue Asp-273 suggests a crosstalk between zinc and calcium transport in the blood (By similarity). The rank order of affinity is zinc > calcium > magnesium (By similarity). Binds to the bacterial siderophore enterobactin and inhibits enterobactin-mediated iron uptake of E.coli from ferric transferrin, and may thereby limit the utilization of iron and growth of enteric bacteria such as E.coli (PubMed:6234017). Does not prevent iron uptake by the bacterial siderophore aerobactin (PubMed:6234017)
- Specific Function
- Antioxidant activity
- Gene Name
- ALB
- Uniprot ID
- P02768
- Uniprot Name
- Albumin
- Molecular Weight
- 69365.94 Da
References
- Schmid B, Chung DE, Warnecke A, Fichtner I, Kratz F: Albumin-binding prodrugs of camptothecin and doxorubicin with an Ala-Leu-Ala-Leu-linker that are cleaved by cathepsin B: synthesis and antitumor efficacy. Bioconjug Chem. 2007 May-Jun;18(3):702-16. Epub 2007 Mar 23. [Article]
- Wang ZM, Ho JX, Ruble JR, Rose J, Ruker F, Ellenburg M, Murphy R, Click J, Soistman E, Wilkerson L, Carter DC: Structural studies of several clinically important oncology drugs in complex with human serum albumin. Biochim Biophys Acta. 2013 Dec;1830(12):5356-74. doi: 10.1016/j.bbagen.2013.06.032. Epub 2013 Jul 6. [Article]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Translocates drugs and phospholipids across the membrane (PubMed:2897240, PubMed:35970996, PubMed:8898203, PubMed:9038218). Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of phosphatidylcholine, phosphatidylethanolamine, beta-D-glucosylceramides and sphingomyelins (PubMed:8898203). Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells (PubMed:2897240, PubMed:35970996, PubMed:9038218)
- Specific Function
- Abc-type xenobiotic transporter activity
- Gene Name
- ABCB1
- Uniprot ID
- P08183
- Uniprot Name
- ATP-dependent translocase ABCB1
- Molecular Weight
- 141477.255 Da
References
- Li D, Jang SH, Kim J, Wientjes MG, Au JL: Enhanced drug-induced apoptosis associated with P-glycoprotein overexpression is specific to antimicrotubule agents. Pharm Res. 2003 Jan;20(1):45-50. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Broad substrate specificity ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes a wide variety of physiological compounds, dietary toxins and xenobiotics from cells (PubMed:11306452, PubMed:12958161, PubMed:19506252, PubMed:20705604, PubMed:28554189, PubMed:30405239, PubMed:31003562). Involved in porphyrin homeostasis, mediating the export of protoporphyrin IX (PPIX) from both mitochondria to cytosol and cytosol to extracellular space, it also functions in the cellular export of heme (PubMed:20705604, PubMed:23189181). Also mediates the efflux of sphingosine-1-P from cells (PubMed:20110355). Acts as a urate exporter functioning in both renal and extrarenal urate excretion (PubMed:19506252, PubMed:20368174, PubMed:22132962, PubMed:31003562, PubMed:36749388). In kidney, it also functions as a physiological exporter of the uremic toxin indoxyl sulfate (By similarity). Also involved in the excretion of steroids like estrone 3-sulfate/E1S, 3beta-sulfooxy-androst-5-en-17-one/DHEAS, and other sulfate conjugates (PubMed:12682043, PubMed:28554189, PubMed:30405239). Mediates the secretion of the riboflavin and biotin vitamins into milk (By similarity). Extrudes pheophorbide a, a phototoxic porphyrin catabolite of chlorophyll, reducing its bioavailability (By similarity). Plays an important role in the exclusion of xenobiotics from the brain (Probable). It confers to cells a resistance to multiple drugs and other xenobiotics including mitoxantrone, pheophorbide, camptothecin, methotrexate, azidothymidine, and the anthracyclines daunorubicin and doxorubicin, through the control of their efflux (PubMed:11306452, PubMed:12477054, PubMed:15670731, PubMed:18056989, PubMed:31254042). In placenta, it limits the penetration of drugs from the maternal plasma into the fetus (By similarity). May play a role in early stem cell self-renewal by blocking differentiation (By similarity)
- Specific Function
- Abc-type xenobiotic transporter activity
- Gene Name
- ABCG2
- Uniprot ID
- Q9UNQ0
- Uniprot Name
- Broad substrate specificity ATP-binding cassette transporter ABCG2
- Molecular Weight
- 72313.47 Da
References
- Ma Y, Wink M: The beta-carboline alkaloid harmine inhibits BCRP and can reverse resistance to the anticancer drugs mitoxantrone and camptothecin in breast cancer cells. Phytother Res. 2010 Jan;24(1):146-9. doi: 10.1002/ptr.2860. [Article]
Drug created at September 11, 2007 17:49 / Updated at January 07, 2021 03:11