Anticancer therapeutics

Desai AA, Innocenti F, Ratain MJ. Pharmacogenomics Road to anticancer therapeutics in nirvana Oncogene 2003 22 6621-6628. 

Small-Molecule Inhibitors of Glutathione S-Transferase PI-1 as Anticancer Therapeutic Agents... 

The BCRP is an ABC transporter similar to P-gp whose expression results in resistance to anticancer therapeutics and may limit intestinal absorption of drugs. However, there have been limited studies to elucidate the selectivities of dmgs for P-gp and BCRP (Brooks et al. 2004). We used a published dataset of seven topoisomerase inhibitors (Maliepaard et al. 2001) to construct a HipHop model for BCRP. We then mapped the potent tyrosine kinase inhibitor Gleevec to this pharmacophore as this compound has been suggested experimentally in conflicting studies as both a substrate and inhibitor of BCRP (Burger et al. 2004 Houghton et al. 2004). 

Board R, Jayson GC. 2005. Platelet-derived growth factor receptor (PDGFR) a target for anticancer therapeutics. Dmg Resist Updates 8 75-83. 

Organometallic osmium-carbonyl clusters such as [Os3(CO)10(NCCH3)2] are apoptosis-inducing agents with anticancer therapeutic potential. The mechanism appears to involve the loss of the labile acetonitrile ligand [85]. 

A comprehensive review of recent advances on organotin anticancer therapeutics has been recently published [172]. 

Rackham O, Nichols SJ, Leedman PJ, Bemers-Price SJ, Filipovska A (2007) A gold(I) phosphine complex selectively induces apoptosis in breast cancer cells implications for anticancer therapeutics targeted to mitochondria. Biochem Pharmacol 74 992-1002... 

Lu, Y. and Low, P.S. (2002) Folate-mediated delivery of macromolecular anticancer therapeutic agents. Adv. Drug Delivery Rev. 54,675-693. 

Transforming growth factor-a-Pseudomonas aeruginosa exotoxin A 40 (TGFa-PE40, Mr = 44,960) is a recombinant fusion protein synthesized in E. co/z.127,128 The growth factor moiety binds to surface epidermal growth factor (EGF) receptors on cancerous cells and is internalized where it releases the exotoxin domain into the cytosol.128 The toxin subunit catalytically inactivates the protein synthesis machinery of the cancer cell and the cell subsequently dies.129 It is a recombinant protein intended to be an anticancer therapeutic. 

One bis(jS-diketonato)Ti compoimd (budotitane) (9) has demonstrated anticancer activity and has been tested in the treatment of colon cancer. It and the more extensively studied organometalhc compound Cp2TiCl2 are thus potential anticancer therapeutics (see also Metal-based Drugs). 

Hakimelahi, G.H. Gassanov, G.S. Hsu, M.-H. Hwua, J.R. Hakimelahi, S. A novel approach towards studying non-genotoxic enediynes as potential anticancer therapeutics. Bioorg. Med. Chem. 2002, 10, 1321-1328. 

Balakin, K. V., Ivanenkov, Y. A., Tkachenko, S. E., Kiselyov, A. S., and Ivachtchenko, A. V. (2008) Regulators of chemokine receptor activity as promising anticancer therapeutics. Curr. Cancer Drug Targets 8, 299-340. 

Chen JS, Faller DV, Spanjaard RA (2003) Short-chain fatty acid inhibitors of histone deacetylases promising anticancer therapeutics Curr Cancer Drug Targets 3(3) 219-236... 

In summary, chemokines are released locally and their effects are usually confined to local tissues, unlike cytokines that often cause systemic effects. Because of these characteristics, they can provide better targets for drug therapy that show less off-target side effects. Chemokine-chemokine receptor systems described in this chapter may provide examples of targets for anticancer therapeutics. 

Although no recent activity has been reported in this field, it remains possible that more potent inhibitors of this enzyme have potential applications as anticancer therapeutics. It is also possible that the combination of salvage uridine-cytidine monophosphate synthesis inhibitors with inhibitors of de novo uridine-cytidine monophosphate synthesis (such as PALA or pyrazofurin) may result in more efficacious cancer therapeutics. 

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