NAV

Thymectacin

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
3D
Similar Structures
Weight
Average: 574.321
Monoisotopic: 573.051179
Chemical Formula
C21H25BrN3O9P
Synonyms
  • Brivudine phosphoramidate
External IDs
  • NB-1011
  • NB1011
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Pharmacology

Indication

Investigated for use/treatment in colorectal cancer.

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Contraindications & Blackbox Warnings
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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.

TargetActionsOrganism
UThymidylate synthaseNot 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

Adverse Effects
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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

Products

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International/Other Brands
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
  1. 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]
  2. 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]
  3. 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]
  4. 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]
  5. 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]
  6. 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]
  7. 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]
PubChem Compound
6440764
PubChem Substance
347827711
ChemSpider
4945015
Wikipedia
Thymectacin

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1, 2CompletedTreatmentTumor1
1, 2Unknown StatusTreatmentColorectal Cancer1

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 Solubility0.0809 mg/mLALOGPS
logP1.33ALOGPS
logP1.26Chemaxon
logS-3.8ALOGPS
pKa (Strongest Acidic)9.62Chemaxon
pKa (Strongest Basic)-3.2Chemaxon
Physiological Charge0Chemaxon
Hydrogen Acceptor Count6Chemaxon
Hydrogen Donor Count3Chemaxon
Polar Surface Area152.73 Å2Chemaxon
Rotatable Bond Count11Chemaxon
Refractivity124.59 m3·mol-1Chemaxon
Polarizability50.22 Å3Chemaxon
Number of Rings3Chemaxon
Bioavailability0Chemaxon
Rule of FiveNoChemaxon
Ghose FilterNoChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleYesChemaxon
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-00di-0000290000-6ab0ce98007abc016322
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-00di-0000590000-f09e36deeed7c104d942
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-0600-1192650000-2239a3f584377d416b40
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-0002-3020930000-a5a8b2a83f07b1ddeb8b
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-014l-3492130000-f21655f2f39db27dd43f
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-0f6x-7903520000-128e38cfbd6f10da97cc
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-211.72234
predicted
DeepCCS 1.0 (2019)
[M+H]+213.61775
predicted
DeepCCS 1.0 (2019)
[M+Na]+219.28271
predicted
DeepCCS 1.0 (2019)

Targets

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Details1. Thymidylate synthase
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