Kinase Inhibitor Identification and Drug Development

At Structure Based Design, Inc, a kinase drug discovery project can be initialized by protein expression, assay development, inhibitor screening, and co-crystal structure determination. We are able to use several methodologies to identify kinase inhibitor for optimization. Over the years, SBD helped identify lead compounds which have led to drug candidates in clinical trials, most notably Tomivosertib (eFT508), which is currently in multiple phase II trials (eFT508 case study here). Following identification, SBD can optimize leads into drug candidates for clinical trials via structure-based design. Our services in the past have been used to aid in the development of drug candidates against kinases such as Aurora A, PKM2, EGFR, MNK, MST1/2, ALK, RIP1, ABL1, CDK6, etc.

  • In silico screening- More than one hundred million commercially available compounds from the ZINC structural libraries for virtual screening. After building up a structure model of kinase, we can dock million lead-like commercially available molecules DOCK software. From this virtual screen, 30 high- ranking compounds were selected and purchased for testing. In our PKM2 study case, 5 of which were active. One compound IC50 potency reached 10 uM. The compound was identified at a PKM2 in an allosteric site in co-crystal structure successfully determined in less than three weeks after initializing the virtual screening.

  • Screening inhibitor using in-house compound libraries- Structure Based Design, Inc has two compound screens in house for hit identification:
    1. Maybridge HitFinder™

      The library comprises 14,400 premier compounds representing the drug-like diversity of the Maybridge screening collection, offering easy and rapid lead identification.

    2. Life Chemicals Collection

      The Life Chemicals Collection of small organic molecules for high-throughput screening contains about 30K+ compounds, having optimal physicochemical parameters for drug discovery. The compounds are original, carefully selected, diverse, well-characterized and pure, lead-like and drug-like new chemical entities.

  • Design of novel kinase inhibitors through the fragment-based approach- The fragment-based design approach links fragments with low initial affinities resulting in high affinity drug-like compounds with relatively small sizes compared to molecules identified from typical screening methods. The small sizes of the compounds from the fragment-based approach gives chemists ample chemical space with which to optimize potency, selectivity and DMPK properties, and as such kinases are already targets of many successful therapeutics. MNK discovery via FBDD is a very successful FBDD case that develop a first-in-class drug candidate in less than two years (link to acticle in J. Med. Chem.). The resultant drug, eFT508, is currently in multiple phase II clinical trials

Contact us at to inquire about our kinase drug development services