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Identification
NameCamptothecin
Accession NumberDB04690
Typesmall molecule
Groupsexperimental
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]

Structure
Thumb
Synonyms
SynonymLanguageCode
(+)-camptothecinNot AvailableNot Available
(+)-camptothecineNot AvailableNot Available
(s)-(+)-camptothecinNot AvailableNot Available
(s)-camptothecinNot AvailableNot Available
20(S)-CamptothecinNot AvailableNot Available
21,22-Secocamptothecin-21-oic acid lactoneNot AvailableNot Available
CamptothecineNot AvailableNot Available
D-camptothecinNot AvailableNot Available
SaltsNot Available
Brand namesNot Available
Brand mixturesNot Available
Categories
CAS number7689-03-4
WeightAverage: 348.352
Monoisotopic: 348.11100701
Chemical FormulaC20H16N2O4
InChI KeyVSJKWCGYPAHWDS-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(11),3,5,7,9,15(20)-heptaene-14,18-dione
SMILES
CC[C@@]1(O)C(=O)OCC2=C1C=C1N(CC3=CC4=CC=CC=C4N=C13)C2=O
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassAlkaloids and Derivatives
ClassCamptothecins
SubclassNot Available
Direct parentCamptothecins
Alternative parentsPyranopyridines; Quinolines and Derivatives; Pyridinones; Benzene and Substituted Derivatives; Tertiary Alcohols; Carboxylic Acid Esters; Dialkyl Ethers; Polyamines
Substituentsquinoline; pyranopyridine; pyridinone; benzene; pyridine; tertiary alcohol; carboxylic acid ester; carboxylic acid derivative; polyamine; dialkyl ether; alcohol; organonitrogen compound
Classification descriptionThis compound belongs to the 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).
Pharmacology
IndicationInvestigated for the treatment of cancer.
PharmacodynamicsCamptothecin 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 actionCamptothecin binds to the topoisomerase I and DNA complex (the covalent complex) resulting in a ternary complex, and thereby stabilizing it. This prevents DNA relegation and therefore causes DNA damage which results in apoptosis.
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
Metabolism
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityAcute oral toxicity (LD50) in mouse: 50.1 mg/kg
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
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 substrate Non-inhibitor 0.907
CYP450 2D6 substrate Non-inhibitor 0.9232
CYP450 2C19 substrate Non-inhibitor 0.9025
CYP450 3A4 substrate 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
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point275-277 °CVolkmann
logP1.74HANSCH,C ET AL. (1995)
Predicted Properties
PropertyValueSource
water solubility5.11e-01 g/lALOGPS
logP1.91ALOGPS
logP1.22ChemAxon
logS-2.8ALOGPS
pKa (strongest acidic)11.71ChemAxon
pKa (strongest basic)3.07ChemAxon
physiological charge0ChemAxon
hydrogen acceptor count4ChemAxon
hydrogen donor count1ChemAxon
polar surface area79.73ChemAxon
rotatable bond count1ChemAxon
refractivity94.49ChemAxon
polarizability36.4ChemAxon
number of rings5ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
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 Reference
  1. Wall ME, Wani MC: Camptothecin and taxol: from discovery to clinic. J Ethnopharmacol. 1996 Apr;51(1-3):239-53; discussion 253-4. Pubmed
  2. 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
ResourceLink
KEGG CompoundC01897
PubChem Compound24360
PubChem Substance46507644
ChemSpider22775
ChEBI27656
ChEMBL
PharmGKBPA153590860
HETEHD
WikipediaCamptothecin
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSshow(73.9 KB)
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

1. DNA topoisomerase 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
DNA topoisomerase 1 P11387 Details

References:

  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  2. Teicher BA: Next generation topoisomerase I inhibitors: Rationale and biomarker strategies. Biochem Pharmacol. 2007 Oct 22;. Pubmed
  3. van der Merwe M, Bjornsti MA: Mutation of GLY721 alters DNA topoisomerase I active site architecture and sensitivity to camptothecin. J Biol Chem. 2007 Dec 4;. Pubmed
  4. 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. Pubmed

Transporters

1. Multidrug resistance protein 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Multidrug resistance protein 1 P08183 Details

References:

  1. 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. Pubmed

2. ATP-binding cassette sub-family G member 2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
ATP-binding cassette sub-family G member 2 Q9UNQ0 Details

References:

  1. 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. Pubmed

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Drug created on September 11, 2007 11:49 / Updated on September 16, 2013 17:25