title: Recent discovery of non-nucleobase thymidine phosphorylase inhibitors targeting cancer.
abstract: Thymidine phosphorylase (TP, EC 2.4.2.4), an enzyme involved in pyrimidine salvage pathway, is identical to platelet-derived endothelial cell growth factor (PD-ECGF) and gliostatin. It is extremely upregulated in a variety of solid tumours. The TP amplification is associated with concomitant overexpression of many angiogenic factors such as matrix metalloproteases (MMPs), interleukins (ILs), vascular endothelial growth factor (VEGF) etc., resulting in promotion of angiogenesis and cancer metastasis. In addition, overshooting TP level protects tumour cells from apoptosis and helps cell survival. Thus, TP is identified as a prime target for developing novel anticancer therapies. Pioneering research activities investigated a large number of TP inhibitors, most of which are pyrimidine or purine analogues. Recently, an array of structurally diverse non-nucleobase derivatives was designed, synthesized and established as promising TP inhibitors. This review, following an outline on the TP structure and functions, gives an overview of the recent advancement of various non-nucleobase TP inhibitors as novel anti-cancer agents.
authors: Faculty of Pharmacy, AIMST University, Semeling, Kedah, 08100, Malaysia. Electronic address: hriday.bera1@gmail.com.
authors: Hriday
authors: H
authors: Bera
authors: Faculty of Pharmacy, AIMST University, Semeling, Kedah, 08100, Malaysia.
authors: Sridevi
authors: S
authors: Chigurupati
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D063646:Carcinogenesis / Q000187:drug effects; D055808:Drug Discovery / Q000379:methods*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D013939:Thymidine Phosphorylase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D013939:Thymidine Phosphorylase
keywords: Angiogenesis; Cancer therapy; Enzyme inhibition; Non-nucleobase inhibitors; Thymidine phosphorylase