Thymectacin

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{{Drugbox | Verifiedfields = changed | Watchedfields = changed | verifiedrevid = 451224667 | IUPAC_name = (2S)-methyl 2-((((2R,3S,5R)-5-(5-((E)-2-bromovinyl)-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-3-hydroxytetrahydrofuran-2-yl)methoxy)(phenoxy)phosphorylamino)propanoate | image = Thymectacin.svg | alt = Skeletal formula of thymectacin | width = 260 | image2 = Thymectacin-3D-spacefill.png | alt2 = Space-filling model of the thymectacin molecule | width2 = 240

| tradename = | pregnancy_category = | legal_status = | routes_of_administration =

| bioavailability = | metabolism = | elimination_half-life = | excretion =

| CAS_number_Ref =  Yes check.svgY | CAS_number = 232925-18-7 | UNII_Ref =  Yes check.svgY | UNII = 2ZRZ4TSW3F | PubChem = 6440764| ChemSpiderID_Ref =  X mark.svgN | ChemSpiderID = 4945015 | synonyms = NB-1011; NB-101; N-[[5-[(E)-2-Bromovinyl]-2'-deoxyuridin-5'-O-yl]](phenoxy)phosphoryl]-L-alanine methyl ester

| C=21 | H=25 | Br=1 | N=3 | O=9 | P=1 | smiles = C[C@@H](C(=O)OC)NP(=O)(OC[C@@H]1[C@H](C[C@@H](O1)n2cc(c(=O)[nH]c2=O)/C=C/Br)O)Oc3ccccc3 | StdInChI_Ref =  X mark.svgN | StdInChI = 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 | StdInChIKey_Ref =  X mark.svgN | StdInChIKey = CFBLUORPOFELCE-BACVZHSASA-N }}

Thymectacin (NB-1011, NB-101) is an experimental anticancer prodrug of brivudine monophosphate. It is being developed by New Biotics and it entered in phase I clinical trials for colon cancer in 2006. [1]

Thymectacin is a small molecule phosphoramidate derivative of (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVdU) with potential antineoplastic activity. [2] It is selectively active against tumor cells expressing high levels of thymidylate synthase (TS). Thymectacin is converted intracellularly by TS to bromovinyldeoxyuridine monophosphate (BVdUMP) which competes with the natural substrate, deoxyuridine monophosphate, for binding to TS. Unlike TS inhibitors, this agent is a reversible substrate for TS catalysis. Thus, TS retains activity and converts BVdUMP into cytotoxic metabolites.

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References

  1. Wilson RH (October 2006). "Novel therapeutic developments other than EGFR and VEGF inhibition in colorectal cancer". The Oncologist. 11 (9): 1018–24. doi: 10.1634/theoncologist.11-9-1018 . PMID   17030644.
  2. "Brivudine phosphoramidate". NCI Drug Dictionary. National Institutes of Health.