Identification

Name
Camptothecin
Accession Number
DB04690
Type
Small Molecule
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]

Structure
Thumb
Synonyms
  • (+)-camptothecin
  • (+)-camptothecine
  • (s)-(+)-camptothecin
  • (s)-camptothecin
  • 20(S)-Camptothecin
  • 21,22-Secocamptothecin-21-oic acid lactone
  • Camptothecine
  • D-camptothecin
Categories
UNII
XT3Z54Z28A
CAS number
7689-03-4
Weight
Average: 348.352
Monoisotopic: 348.11100701
Chemical Formula
C20H16N2O4
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[11.8.0.0²,¹¹.0⁴,⁹.0¹⁵,²⁰]henicosa-1(21),2,4,6,8,10,15(20)-heptaene-14,18-dione
SMILES
CC[[email protected]@]1(O)C(=O)OCC2=C1C=C1N(CC3=CC4=CC=CC=C4N=C13)C2=O

Pharmacology

Indication

Investigated for the treatment of cancer.

Structured Indications
Not Available
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 (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.

TargetActionsOrganism
UDNA topoisomerase 1Not AvailableHuman
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
Toxicity

Acute oral toxicity (LD50) in mouse: 50.1 mg/kg

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Camptothecin.Approved
AcetyldigoxinAcetyldigoxin may decrease the cardiotoxic activities of Camptothecin.Experimental
BevacizumabBevacizumab may increase the cardiotoxic activities of Camptothecin.Approved, Investigational
CabazitaxelThe risk or severity of adverse effects can be increased when Cabazitaxel is combined with Camptothecin.Approved
CyclophosphamideCyclophosphamide may increase the cardiotoxic activities of Camptothecin.Approved, Investigational
CymarinCymarin may decrease the cardiotoxic activities of Camptothecin.Experimental
DeslanosideDeslanoside may decrease the cardiotoxic activities of Camptothecin.Approved
DigitoxinDigitoxin may decrease the cardiotoxic activities of Camptothecin.Approved, Investigational
DigoxinDigoxin may decrease the cardiotoxic activities of Camptothecin.Approved
Digoxin Immune Fab (Ovine)Digoxin Immune Fab (Ovine) may decrease the cardiotoxic activities of Camptothecin.Approved
DocetaxelThe risk or severity of adverse effects can be increased when Docetaxel is combined with Camptothecin.Approved, Investigational
EltrombopagThe serum concentration of Camptothecin can be increased when it is combined with Eltrombopag.Approved
GitoformateGitoformate may decrease the cardiotoxic activities of Camptothecin.Experimental
Lanatoside CLanatoside C may decrease the cardiotoxic activities of Camptothecin.Experimental
LumacaftorThe serum concentration of Camptothecin can be decreased when it is combined with Lumacaftor.Approved
MetildigoxinMetildigoxin may decrease the cardiotoxic activities of Camptothecin.Experimental
OleandrinOleandrin may decrease the cardiotoxic activities of Camptothecin.Experimental, Investigational
OuabainOuabain may decrease the cardiotoxic activities of Camptothecin.Approved
PaclitaxelThe risk or severity of adverse effects can be increased when Paclitaxel is combined with Camptothecin.Approved, Vet Approved
PeruvosidePeruvoside may decrease the cardiotoxic activities of Camptothecin.Experimental
ProscillaridinProscillaridin may decrease the cardiotoxic activities of Camptothecin.Experimental
RanolazineThe serum concentration of Camptothecin can be increased when it is combined with Ranolazine.Approved, Investigational
RolapitantThe serum concentration of Camptothecin can be increased when it is combined with Rolapitant.Approved
TeriflunomideThe serum concentration of Camptothecin can be increased when it is combined with Teriflunomide.Approved
TrastuzumabTrastuzumab may increase the cardiotoxic activities of Camptothecin.Approved, Investigational
Food Interactions
Not 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 References
  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:9213622]
  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:5357525]
External Links
KEGG Compound
C01897
PubChem Compound
24360
PubChem Substance
46507644
ChemSpider
22775
BindingDB
50008923
ChEBI
27656
ChEMBL
CHEMBL65
PharmGKB
PA153590860
HET
EHD
Wikipedia
Camptothecin
PDB Entries
1t8i
MSDS
Download (73.9 KB)

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)275-277 °CVolkmann
logP1.74HANSCH,C ET AL. (1995)
Predicted Properties
PropertyValueSource
Water Solubility0.511 mg/mLALOGPS
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 Area79.73 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity94.49 m3·mol-1ChemAxon
Polarizability36.4 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.841
Blood Brain Barrier-0.6345
Caco-2 permeable-0.5555
P-glycoprotein substrateSubstrate0.6039
P-glycoprotein inhibitor INon-inhibitor0.7852
P-glycoprotein inhibitor IINon-inhibitor0.9762
Renal organic cation transporterNon-inhibitor0.8376
CYP450 2C9 substrateNon-substrate0.8311
CYP450 2D6 substrateNon-substrate0.8454
CYP450 3A4 substrateSubstrate0.546
CYP450 1A2 substrateInhibitor0.9106
CYP450 2C9 inhibitorNon-inhibitor0.907
CYP450 2D6 inhibitorNon-inhibitor0.9232
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorInhibitor0.7959
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.5591
Ames testNon AMES toxic0.5393
CarcinogenicityNon-carcinogens0.8187
BiodegradationNot ready biodegradable1.0
Rat acute toxicity3.3261 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9939
hERG inhibition (predictor II)Non-inhibitor0.902
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
MS/MS Spectrum - Linear Ion Trap , negativeLC-MS/MSsplash10-0udi-0009000000-d761f92f05da35fcdccc
MS/MS Spectrum - Linear Ion Trap , positiveLC-MS/MSsplash10-0a4i-0009000000-f0c6f4a14bb1034d2b44
MS/MS Spectrum - Linear Ion Trap , positiveLC-MS/MSsplash10-004i-0009000000-21af02e2bc86f07c0100
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0002-0149000000-a4935b6e6f5d88de2237

Taxonomy

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
Camptothecin / Pyranopyridine / Quinoline / Pyridinone / Pyridine / Benzenoid / Heteroaromatic compound / Tertiary alcohol / Carboxylic acid ester / Lactam
show 16 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
quinoline alkaloid, pyranoindolizinoquinoline (CHEBI:27656) / Alkaloids, Quinoline alkaloids (C01897)

Targets

Details
1. DNA topoisomerase 1
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Poly(a) rna binding
Specific 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 singl...
Gene Name
TOP1
Uniprot ID
P11387
Uniprot Name
DNA topoisomerase 1
Molecular Weight
90725.19 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  2. Teicher BA: Next generation topoisomerase I inhibitors: Rationale and biomarker strategies. Biochem Pharmacol. 2008 Mar 15;75(6):1262-71. Epub 2007 Oct 22. [PubMed:18061144]
  3. 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. [PubMed:18056711]
  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:10592235]

Carriers

Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. 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. [PubMed:17378599]
  2. 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. [PubMed:23838380]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
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:12608535]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Xenobiotic-transporting atpase activity
Specific Function
High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both fro...
Gene Name
ABCG2
Uniprot ID
Q9UNQ0
Uniprot Name
ATP-binding cassette sub-family G member 2
Molecular Weight
72313.47 Da
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. doi: 10.1002/ptr.2860. [PubMed:19548284]

Drug created on September 11, 2007 11:49 / Updated on November 09, 2017 03:45