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Cancer is still generating the most new pharma industry-derived drug candidates, according to the measure of numbers of novel compounds reported at the recent biannual American Chemical Society (ACS), held in San Francisco, and verified by Citeline’s Pharmaprojects. But, after a summer of intense press coverage on the lack of industry effort to find new anti-infectives, there were also an encouraging number of new molecules in this area presented.



Amongst highlights in oncology, Genentech reported a pan-Pim kinase inhibitor for the treatment of multiple myeloma ; not to be outdone; Amgen also provided details and a lead structure of its series of their Pim kinase inhibitors:






Also, in oncology, a completely new target was reported by Genentech, which is developing a substituted 4-hydroxy-5,6-dihydropyran-2-one which inhibits human lactate dehydrogenase A (LDHA). This is quite a daring concept, due to the high abundance of cellular LDHA, as well as its catalytic site having a highly hydrophilic nature.



In the infectious diseases area, Actelion gave details of its tetrahydropyran-based topoisomerase inhibitors, in development for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections. UK-based Redx Anti-Infectives also provided information on new antibacterials, disclosing a series of small-molecule 3-methoxybenzamide analogs as FtsZ inhibitors for the treatment of drug-resistant staphylococcal infections. In viral infections, hepatitis-C continues to be hot, with Vertex providing insight into its latest projects: a series of HCV NS5A genotype 1a, 1b inhibitors, and a second series of lactam-containing non-nucleoside HCV NS5B inhibitors (lead structure shown below):






A number of neurological products were also disclosed, with Suven Life Sciences developing early stage 5-HT4 receptor agonists for the treatment of Alzheimer’s disease; Bristol-Myers Squibb working on BMS-955829, a positive allosteric modulator of mGluR5, as a schizophrenia therapy; and Eli Lilly developing metabotropic glutamate 2/3 antagonists for the treatment of depression. In the cardiovascular space, Gilead provided details on its Nav 1.5 sodium channel inhibitor, GS-462808, which is in early stage development for ischaemic heart disease. Additionally, AstraZeneca presented information on AZD-3971, a trioxoisothiazole-based liver receptor X (LXR) agonist, that is aimed at the treatment of atherosclerosis; and Kowa also produced a poster containing a structure on their LXRβ agonist, K-20770-2b, also in development for atherosclerosis.



Although this is only a small sample of the many products revealed at this conference, it does highlight that such meetings are still key conduits for the dissemination of information on novel compounds and structural classes for the treatment of a variety of conditions.

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