Thymectacin

• CAT Number: I009672
• CAS Number: 827031-83-4
• Molecular Formula: C17H17N3O
• Molecular Weight: 279.343
• Purity: ≥95%
• Solubility: Soluble in DMSO, not in water
• Storage: 0 - 4 °C for short term, or -20 °C for long term
• IUPAC Name: N-(4-methoxyphenyl)-N,2-dimethylquinazolin-4-amine
• InChI: InChI=1S/C17H17N3O/c1-12-18-16-7-5-4-6-15(16)17(19-12)20(2)13-8-10-14(21-3)11-9-13/h4-11H,1-3H3
• InChIKey: SNHCRNMVYDHVDT-UHFFFAOYSA-N
• SMILES: CC1=NC2=CC=CC=C2C(=N1)N(C)C3=CC=C(C=C3)OC

Thymectacin, also known as NB-1011, is a small molecule phosphoramidate derivative of (E)-5-(2-bromovinyl)-2/’-deoxyuridine with potential antineoplastic activity. Selectively active against tumor cells expressing high levels of thymidylate synthase (TS), BVdU pronucleotide analogue NB1011 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.

Reference

1:Bioorg Med Chem. 2005 May 2;13(9):3219-27. Anti-cancer ProTides: tuning the activity of BVDU phosphoramidates related to thymectacin.McGuigan C,Thiery JC,Daverio F,Jiang WG,Davies G,Mason M, PMID: 15809157 DOI: 10.1016/j.bmc.2005.02.041 Abstract: Based on our wide ranging knowledge of phosphoramidate ProTides as anti-viral agents we have tuned the lead anti-cancer agent thymectacin in the ester and amino acid regions and revealed a substantial enhancement in in vitro potency versus colon and prostate cancer cell lines. Twelve analogues have been reported, with yields of 29-78%. The compounds are fully characterised and data clearly reveal the presence of two phosphate diastereoisomers, as expected, in roughly equi-molar proportions. The compounds were evaluated in tissue culture versus three different tumour cell lines, using thymectacin as the control. It is notable that minor structural modification of the parent phenyl methoxyalaninyl structure of thymectacin leads to significant enhancements in potency. In particular, replacement of the methyl ester moiety in the lead by a benzyl ester gave a 175-fold boost in potency versus colon cancer HT115. This derivative emerges as a low micromolar inhibitor of HT115 cells and a new lead for further optimisation.