Cositecan
Explore a selection of our essential drug information below, or:
Identification
- Generic Name
- Cositecan
- DrugBank Accession Number
- DB05806
- Background
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.
- Type
- Small Molecule
- Groups
- Investigational
- Structure
- Weight
- Average: 448.5863
Monoisotopic: 448.181833927 - Chemical Formula
- C25H28N2O4Si
- Synonyms
- Cositecan
- Karenitecin
- External IDs
- BNP 1350
- BNP1350
- DB 172
Pharmacology
- Indication
Investigated for use/treatment in brain cancer, lung cancer, and melanoma.
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- 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.
Target Actions Organism ADNA 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
Not Available
- 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.Not Available
- 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 9 more
- Substituents
- Alcohol / Alkylsilane / Aromatic heteropolycyclic compound / Azacycle / Benzenoid / Camptothecin / Carbonyl group / Carboxylic acid derivative / Carboxylic acid ester / Heteroaromatic compound show 20 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- 24R60NVC41
- CAS number
- 203923-89-1
- 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[11.8.0.0^{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=C(CC[Si](C)(C)C)C4=CC=CC=C4N=C13)C2=O
References
- General References
- 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. [Article]
- 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. [Article]
- 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. [Article]
- External Links
- PubChem Compound
- 148202
- PubChem Substance
- 175427037
- ChemSpider
- 130651
- ChEMBL
- CHEMBL1997373
- ZINC
- ZINC000169746728
- Wikipedia
- Camptothecin
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample data3 Completed Treatment Ovarian Cancer 1 somestatus stop reason just information to hide 2 Completed Treatment Brain Neoplasm / Malignant Brain Neoplasm 1 somestatus stop reason just information to hide 2 Completed Treatment Lung Cancer 1 somestatus stop reason just information to hide 2 Completed Treatment Melanoma / Neoplasm 1 somestatus stop reason just information to hide 2 Completed Treatment Primary Peritoneal Carcinoma / Recurrent Ovarian Carcinoma 1 somestatus stop reason just information to hide
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
Property Value Source Water Solubility 0.0194 mg/mL ALOGPS logP 3.84 ALOGPS logP 2.4 Chemaxon logS -4.4 ALOGPS pKa (Strongest Acidic) 11.71 Chemaxon pKa (Strongest Basic) 3.86 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 4 Chemaxon Refractivity 120.05 m3·mol-1 Chemaxon Polarizability 48.96 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 - 0.7457 Blood Brain Barrier - 0.7671 Caco-2 permeable - 0.6032 P-glycoprotein substrate Substrate 0.8337 P-glycoprotein inhibitor I Non-inhibitor 0.5903 P-glycoprotein inhibitor II Non-inhibitor 0.9237 Renal organic cation transporter Non-inhibitor 0.8356 CYP450 2C9 substrate Non-substrate 0.8447 CYP450 2D6 substrate Non-substrate 0.8188 CYP450 3A4 substrate Substrate 0.7013 CYP450 1A2 substrate Non-inhibitor 0.6461 CYP450 2C9 inhibitor Non-inhibitor 0.8858 CYP450 2D6 inhibitor Non-inhibitor 0.8843 CYP450 2C19 inhibitor Non-inhibitor 0.8195 CYP450 3A4 inhibitor Non-inhibitor 0.5891 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8342 Ames test Non AMES toxic 0.6195 Carcinogenicity Non-carcinogens 0.8209 Biodegradation Not ready biodegradable 0.9952 Rat acute toxicity 2.9058 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9864 hERG inhibition (predictor II) Non-inhibitor 0.8105
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-0002-0000900000-e707fcfec7486098bd45 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-001i-0008900000-a21afc70923488614506 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-0f6t-3007900000-68b51b22e2e38925b1c9 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-0k92-9007400000-e5a1c2823d11583d16e8 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-0002-0029100000-20e995b75f7ac610acec Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-000t-1419600000-6072c05c8b3f0b0b5d41 Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Not Available
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- 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
- Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
Drug created at November 18, 2007 18:27 / Updated at August 26, 2024 19:23