Apoptosis Focused Library
Aberrant apoptosis has been experimentally implicated in a broad variety of illnesses, including AIDS, allograft rejection, restenosis, autoimmunity (lupus, type-I diabetes, rheumatoid arthritis), cancer, heart failure, infectious diseases, inflammation, osteoporosis, trauma and neurodegenerative disorders like Alzheimer’s, Parkinson’s, Huntington’s, ALS, and stroke. Consequently, considerable interest has arisen in therapeutic strategies for modulating apoptosis pharmacologically.
Considering the vast complexity of apoptosis mechanisms, a substantial number of protein targets have been identified and more are likely in the near future. To make matters even more interesting, in certain cases it is desired to preserve cell viability, depending upon discovering anti-apoptotic treatments. In other cases the objective will be to discover pro-apoptosis agents which induce the death of cells that are pathologically resistant. ChemDiv’s collection is divided accordingly with compounds designed for either pro- or anti-apoptosis purposes.
Within our Targeted Diversity Set of focused drug-like libraries biased to apoptotic targets (~20,000 compounds), you will find:
• “Recognition Motifs” Library consisting of peptidomimetics for inhibition of protein- protein interactions (~10,000 compounds)
• Serendipity Library of lead-like fragments (Ro3)/Natural and natural-like compounds (~5,000 compounds)
• Annotated sub-Library Library based on the stem cores (privileged substructures) Sub- sets focused against orthogonal targets (GPCRs, ICh...~5,000 compounds)
In addition, ChemDiv has organized some 30 target-specific sub-libraries (250-750 members each) directed at:
Death associated protein kinase (DAPK) inhibitors
Nerve Growth Factor Receptor LNGFRp75 antagonists
Macrophage migration inhibitory factor (MIF) modulators
Cytochrome C inhibitors
Mitochondria MPP-pores inhibitors
The selection process for the apoptosis collection involves identifying prototypes existing in the patent and research literature and performing bioisosteric replacement strategies or known small peptide ligands are substituted with heterocyclic peptidomimetics. Then a similarity search is conducted within our own collection for possible augmentation of the rational library. Other techniques include computer-assisted 3-D pharmacophore matching and the synthesis of new heterocyclic chemotypes with functionality mimicking known active “warheads.” In some cases, proof of concept has been established with in-house biological data.
Every effort is made to insure that the compounds in our collection possess high intellectual property potential as determined by Bielstein and SciFinder substructure searches resulting in a low number of related hits.