Locus Programs

The Locus internal programs utilize our proprietary computational drug design technology for the discovery and development of novel compounds for the treatment of unmet medical needs. Our primary area of focus is the mitogen-activated protein kinase (MAPK) pathway, which plays a central role in diseases associated with cancer, inflammation, and infection. There are three major classes of MAPKs: p38, JNK, and ERK. These pathways are activated by upstream MAPK kinases and lead to the downstream production of pro-inflammatory cytokines, including tumor necrosis factor alpha (TNFa) and interleukins (IL), such as IL-1 and IL-6.

Our lead development program is an orally active, exclusively allosteric site inhibitor of p38a MAP kinase. The allosteric site on p38, in contrast to the commonly utilized ATP site, provides the structural heterogeneity among kinases to realize a highly selective inhibitor using our structure-based drug design approach. In addition, this alternative mode of binding to p38 could theoretically translate into a biological advantage over ATP site inhibitors.

Locus has other small molecule inhibitors derived from the p38 MAPK chemistry that block other kinases relevant to diseases involving the p38 pathway. These p38-based "multikinase" inhibitors can test new biological hypotheses underlying certain diseases, and may end up confering therapeutic advantages for drug development candidates.

Other discovery projects include an Hsp90 inhibitor program with the National Cancer Institute (NCI), an EPO receptor antagonist for renal cancer with the National Institute of Health (NIH), and a gp41 inhibitor program for AIDS/HIV in association with the International Partnership of Microbicides (IPM).