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Open Position

Principal Scientist/Associate Director of Biochemistry

Full-time role based in Boston, MA or Monmouth Junction, NJ

Within every human cell, nature has engineered finely tuned control mechanisms to correct imbalances caused by stress and disease and promote healing. At HotSpot Therapeutics, nature is inspiring us to create a wave of new medicines.

Through a proprietary technology platform, we are uncovering privileged allosteric sites used by nature to control proteins – called natural hotspots- that can be exploited through small molecule drug discovery. Natural hotspots are allowing sought-after targets to be drugged for the first time while delivering molecules with exquisite selectivity and attractive drug-like properties.

HotSpot is supported by a syndicate of leading healthcare investors based in the US and Europe. You will be joining a seasoned team of drug hunters with an excellent track record in drug discovery.  As a HotSpotter, you are comfortable thinking outside the box and breaking convention. You are curious about the world and contribute beyond your precise role description. You are action oriented and extraordinary at getting things done. You communicate openly with your colleagues, and you hate office politics.

We are seeking an experienced and enthusiastic biochemist to join our growing biochemistry and biophysics team at Hotspot Therapeutics. The successful candidate will lead the biochemical efforts in our drug discovery team to impact the discovery of novel medicines in oncology and inflammatory diseases.  The primary technical responsibilities are development of the biochemical assays, working collaboratively with a multi-disciplinary team of biophysics, cell biology and medicinal chemistry scientists to develop and implement a high-quality biology platform for identification and optimization of the allosteric Inhibitors, the mechanism of action studies of inhibitors and demonstration of the target engagement.

Key Responsibilities:

  • Lead from the bench in the design, development, validation, and implementation of novel biochemistry or enzymology assays for allosteric small molecule screens, mechanism of action studies, and target engagement
  • Provide expert knowledge of biochemical mechanisms of small molecule interactions with target proteins and serve on cross-functional project teams as the biochemistry expert
  • Manage external CROs in assay development, transfer, and validation, maintain the high quality of assays at CROs to support library screens, hit validation, hit to lead, and lead optimization and provide quality control of data entering the corporate database
  • Effectively collaborate with colleagues in biophysics, cell biology, medicinal chemistry to develop and implement a high-quality biology platform to improve compound potency, properties, understanding of MoA of hits and leads, and demonstrate target engagement.
  • Demonstrated track record of accomplishments through use of strong problem-solving skills and ensuring flawless execution of the experiments
  • Design the protein constructs for the assay development and supervise the protein production at CROs
  • Analyze, interpret, and communicate high-quality data to a multi-disciplinary project team
  • Stay current with new technologies and relevant scientific advances in biochemical techniques and assay formats from literature, scientific meetings, and professional network
  • Propose and evaluate new approaches and technologies in early drug discovery
  • Lead the biochemistry aspect of publication and poster presentation



  • Candidates must have a Ph.D. in biochemistry, or related discipline with at least 5+ years of industry experience, or a BS/MS in biochemistry, or a related discipline with 10+ years relevant industry experience
  • In-depth knowledge of biochemical assay development for small molecule drug discovery to support hit ID, hit-to lead and lead optimization, experience in allosteric inhibitors is a plus
  • Experience in using biochemical assays to characterize MOA of the small molecule inhibitors and targets engagement
  • Experience in a wide array of biochemical assay formats, utilizing a variety of readouts such as FI, FP, TR-FRET, AlphaScreen, MSD, DSF.
  • Experience in enzyme kinetics studies and characterization of competitiveness, novel assay formats for identification of allosteric inhibitors
  • Attention to details and excellent troubleshooting and problem-solving skills
  • Demonstrated success using in-house and external resources to advance programs from assay development to lead optimization
  • Strong written and oral communication skills, excellent interpersonal skills, with demonstrated ability to work collaboratively in multidisciplinary teams
  • Experience in working with challenging proteins, studying covalent compounds, fragment-based screening, and DEL is a plus

HotSpot is an equal opportunity employer. We celebrate diversity and are committed to creating an inclusive environment for all employees.


If this role interests you, please email: