Identification
- Generic Name
- Thymectacin
- DrugBank Accession Number
- DB05116
- Background
Thymectacin, a phosphoramidate derivative of (E)-5-(2-bromovinyl)-2'-deoxyuridine, is a novel small molecule anticancer agent. Thymectacin is selectively active against tumor cells expressing high levels of thymidylate synthase (TS), a critical enzyme in DNA biosynthesis. Thymectacin was as efficacious as irinotecan, a drug recently approved for the treatment of 5-fluorouracil-resistant colon cancer.
- Type
- Small Molecule
- Groups
- Investigational
- Structure
Structure for Thymectacin (DB05116)
- Weight
- Average: 574.321
Monoisotopic: 573.051179 - Chemical Formula
- C21H25BrN3O9P
- Synonyms
- Brivudine phosphoramidate
- External IDs
- NB-1011
- NB1011
Pharmacology
- Indication
Investigated for use/treatment in colorectal cancer.
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Avoid life-threatening adverse drug eventsImprove clinical decision support with information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events & improve clinical decision support.- Pharmacodynamics
Not Available
- Mechanism of action
NB1011 targets thymidylate synthase (TS), which catalyzes the transformation of E-5-(2-bromovinyl)-2'-deoxyuridine-5'-monophosphate (BVdUMP) into cytotoxic reaction products. Due to the elevated levels of TS expression in tumor cells compared to normal cells, these cytotoxic products are preferentially generated inside tumor cells, and, as expected, NB1011 is more toxic to cells with higher levels of TS expression. Therefore, NB1011 therapy should kill tumor cells without severely damaging normal cells.
Target Actions Organism UThymidylate synthase Not Available Humans - 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
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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
Products
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- Thymectacin
Categories
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as pyrimidine 2'-deoxyribonucleosides. These are compounds consisting of a pyrimidine linked to a ribose which lacks a hydroxyl group at position 2.
- Kingdom
- Organic compounds
- Super Class
- Nucleosides, nucleotides, and analogues
- Class
- Pyrimidine nucleosides
- Sub Class
- Pyrimidine 2'-deoxyribonucleosides
- Direct Parent
- Pyrimidine 2'-deoxyribonucleosides
- Alternative Parents
- Alpha amino acid esters / Alanine and derivatives / Phenoxy compounds / Phosphoric diester monoamides / Pyrimidones / Hydropyrimidines / Organic phosphoramides / Oxolanes / Heteroaromatic compounds / Vinylogous amides show 14 more
- Substituents
- Alanine or derivatives / Alcohol / Alpha-amino acid ester / Alpha-amino acid or derivatives / Aromatic heteromonocyclic compound / Azacycle / Benzenoid / Bromoalkene / Carbonyl group / Carboxylic acid derivative show 32 more
- Molecular Framework
- Aromatic heteromonocyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- 2ZRZ4TSW3F
- CAS number
- 232925-18-7
- InChI Key
- CFBLUORPOFELCE-BACVZHSASA-N
- InChI
- InChI=1S/C21H25BrN3O9P/c1-13(20(28)31-2)24-35(30,34-15-6-4-3-5-7-15)32-12-17-16(26)10-18(33-17)25-11-14(8-9-22)19(27)23-21(25)29/h3-9,11,13,16-18,26H,10,12H2,1-2H3,(H,24,30)(H,23,27,29)/b9-8+/t13-,16-,17+,18+,35?/m0/s1
- IUPAC Name
- methyl (2S)-2-[({[(2R,3S,5R)-5-{5-[(E)-2-bromoethenyl]-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl}-3-hydroxyoxolan-2-yl]methoxy}(phenoxy)phosphoryl)amino]propanoate
- SMILES
- COC(=O)[C@H](C)NP(=O)(OC[C@H]1O[C@H](C[C@@H]1O)N1C=C(\C=C\Br)C(=O)NC1=O)OC1=CC=CC=C1
References
- General References
- Congiatu C, McGuigan C, Jiang WG, Davies G, Mason MD: Naphthyl phosphoramidate derivatives of BVdU as potential anticancer agents: design, synthesis and biological evaluation. Nucleosides Nucleotides Nucleic Acids. 2005;24(5-7):485-9. [Article]
- Sergeeva OA, Khambatta HG, Cathers BE, Sergeeva MV: Kinetic properties of human thymidylate synthase, an anticancer drug target. Biochem Biophys Res Commun. 2003 Jul 25;307(2):297-300. [Article]
- Dellinger RW, Karjian PL, Neuteboom ST: NB1011 induces Ser15 phosphorylation of p53 and activates the G2/M checkpoint. Anticancer Drugs. 2003 Jul;14(6):449-55. [Article]
- Neuteboom ST, Karjian PL, Boyer CR, Beryt M, Pegram M, Wahl GM, Shepard HM: Inhibition of cell growth by NB1011 requires high thymidylate synthase levels and correlates with p53, p21, bax, and GADD45 induction. Mol Cancer Ther. 2002 Apr;1(6):377-84. [Article]
- Boyer CR, Karjian PL, Wahl GM, Pegram M, Neuteboom ST: Nucleoside transport inhibitors, dipyridamole and p-nitrobenzylthioinosine, selectively potentiate the antitumor activity of NB1011. Anticancer Drugs. 2002 Jan;13(1):29-36. [Article]
- Li Q, Boyer C, Lee JY, Shepard HM: A novel approach to thymidylate synthase as a target for cancer chemotherapy. Mol Pharmacol. 2001 Mar;59(3):446-52. [Article]
- Sergeeva MV, Cathers BE: Cellular transformation of the investigational new anticancer drug NB1011, a phosphoramidate of 5-(2-bromovinyl)-2'-deoxyuridine, results in modification of cellular proteins not DNA. Biochem Pharmacol. 2003 Mar 1;65(5):823-31. [Article]
- External Links
- PubChem Compound
- 6440764
- PubChem Substance
- 347827711
- ChemSpider
- 4945015
- Wikipedia
- Thymectacin
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 1, 2 Completed Treatment Tumor 1 1, 2 Unknown Status Treatment Colorectal Cancer 1
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 0.0809 mg/mL ALOGPS logP 1.33 ALOGPS logP 1.26 Chemaxon logS -3.8 ALOGPS pKa (Strongest Acidic) 9.62 Chemaxon pKa (Strongest Basic) -3.2 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 6 Chemaxon Hydrogen Donor Count 3 Chemaxon Polar Surface Area 152.73 Å2 Chemaxon Rotatable Bond Count 11 Chemaxon Refractivity 124.59 m3·mol-1 Chemaxon Polarizability 50.22 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 0 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not Available
Targets
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Thymidylate synthase activity
- Specific Function
- Contributes to the de novo mitochondrial thymidylate biosynthesis pathway.
- Gene Name
- TYMS
- Uniprot ID
- P04818
- Uniprot Name
- Thymidylate synthase
- Molecular Weight
- 35715.65 Da
Drug created at October 21, 2007 22:23 / Updated at March 11, 2023 21:11