Cositecan

Identification

Logo pink
Are you a
new drug developer?
Contact us to learn more about our customized products and solutions.
Name
Cositecan
Accession Number
DB05806
Type
Small Molecule
Groups
Investigational
Description

Cositecan is the novel camptothecin derivative which is also known as Karenitecin. It has been developed for superior oral bioavailability and increased lactone stability. It is used to treat cancer.

Structure
Thumb
Synonyms
  • Cositecan
  • Karenitecin
External IDs
BNP 1350 / BNP1350 / DB 172
Categories
UNII
24R60NVC41
CAS number
203923-89-1
Weight
Average: 448.5863
Monoisotopic: 448.181833927
Chemical Formula
C25H28N2O4Si
InChI Key
POADTFBBIXOWFJ-VWLOTQADSA-N
InChI
InChI=1S/C25H28N2O4Si/c1-5-25(30)19-12-21-22-17(13-27(21)23(28)18(19)14-31-24(25)29)15(10-11-32(2,3)4)16-8-6-7-9-20(16)26-22/h6-9,12,30H,5,10-11,13-14H2,1-4H3/t25-/m0/s1
IUPAC Name
(19S)-19-ethyl-19-hydroxy-10-[2-(trimethylsilyl)ethyl]-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[C@@]1(O)C(=O)OCC2=C1C=C1N(CC3=C(CC[Si](C)(C)C)C4=CC=CC=C4N=C13)C2=O

Pharmacology

Indication

Investigated for use/treatment in brain cancer, lung cancer, and melanoma.

Pharmacodynamics
Not Available
Mechanism of action

BNP1350, 7-[(2-trimethylsilyl)ethyl]-20(S)-camptothecin, is a novel semi-synthetic, highly lipophilic, silicon-containing camptothecin and an inhibitor of topoisomerase I. It has been supercomputer engineered for superior oral bioavailability, superior lactone stability, broad anti-tumor activity, increased potency and insensitivity to Pgp/MRP/LRP drug resistance.

TargetActionsOrganism
UDNA topoisomerase 1Not AvailableHumans
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
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
  1. Thompson PA, Berg SL, Aleksic A, Kerr JZ, McGuffey L, Dauser R, Nuchtern JG, Hausheer F, Blaney SM: Plasma and cerebrospinal fluid pharmacokinetic study of BNP1350 in nonhuman primates. Cancer Chemother Pharmacol. 2004 Jun;53(6):527-32. Epub 2004 Mar 2. [PubMed:14997342]
  2. Yin MB, Guo B, Vanhoefer U, Azrak RG, Minderman H, Frank C, Wrzosek C, Slocum HK, Rustum YM: Characterization of protein kinase chk1 essential for the cell cycle checkpoint after exposure of human head and neck carcinoma A253 cells to a novel topoisomerase I inhibitor BNP1350. Mol Pharmacol. 2000 Mar;57(3):453-9. [PubMed:10692484]
  3. Van Hattum AH, Pinedo HM, Schluper HM, Hausheer FH, Boven E: New highly lipophilic camptothecin BNP1350 is an effective drug in experimental human cancer. Int J Cancer. 2000 Oct 15;88(2):260-6. [PubMed:11004678]
External Links
PubChem Compound
148202
PubChem Substance
175427037
ChemSpider
130651
ChEMBL
CHEMBL1997373
Wikipedia
Camptothecin

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentBrain and Central Nervous System Tumors1
1CompletedTreatmentCarcinoma NOS / Lung Cancer Non-Small Cell Cancer (NSCLC)1
1, 2TerminatedTreatmentMalignant Melanoma1
2CompletedTreatmentLung Cancers1
2CompletedTreatmentMalignant Neoplasms, Brain / Neoplasms, Brain1
2CompletedTreatmentMelanoma / Neoplasms1
2CompletedTreatmentPrimary Peritoneal Carcinoma / Recurrent Ovarian Carcinoma1
3CompletedTreatmentCancer of the Ovary1

Pharmacoeconomics

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

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0194 mg/mLALOGPS
logP3.84ALOGPS
logP2.4ChemAxon
logS-4.4ALOGPS
pKa (Strongest Acidic)11.71ChemAxon
pKa (Strongest Basic)3.86ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area79.73 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity120.05 m3·mol-1ChemAxon
Polarizability48.96 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.7457
Blood Brain Barrier-0.7671
Caco-2 permeable-0.6032
P-glycoprotein substrateSubstrate0.8337
P-glycoprotein inhibitor INon-inhibitor0.5903
P-glycoprotein inhibitor IINon-inhibitor0.9237
Renal organic cation transporterNon-inhibitor0.8356
CYP450 2C9 substrateNon-substrate0.8447
CYP450 2D6 substrateNon-substrate0.8188
CYP450 3A4 substrateSubstrate0.7013
CYP450 1A2 substrateNon-inhibitor0.6461
CYP450 2C9 inhibitorNon-inhibitor0.8858
CYP450 2D6 inhibitorNon-inhibitor0.8843
CYP450 2C19 inhibitorNon-inhibitor0.8195
CYP450 3A4 inhibitorNon-inhibitor0.5891
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8342
Ames testNon AMES toxic0.6195
CarcinogenicityNon-carcinogens0.8209
BiodegradationNot ready biodegradable0.9952
Rat acute toxicity2.9058 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9864
hERG inhibition (predictor II)Non-inhibitor0.8105
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

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 9 more
Substituents
Camptothecin / Pyranopyridine / Quinoline / Pyridinone / Pyridine / Benzenoid / Heteroaromatic compound / Tertiary alcohol / Carboxylic acid ester / Lactam
show 20 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Humans
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

Drug created on November 18, 2007 11:27 / Updated on June 04, 2019 06:19