HotSpot looks to boost cancer therapy pipeline with Excelra partnership

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U.S. biotech company HotSpot Therapeutics, Inc. is looking to increase its drug development and discovery efforts by partnering with Indian data and digital insights company Excelra.

HotSpot discovers and develops small molecule allosteric therapies for the treatment of cancer and autoimmune diseases. 


What are allosteric therapies?

In the journal ACS Medicinal Chemistry Letters, Ahmed F. Abdel-Magid explains that most current drugs are designed to bind directly to the primary active sites of their biological targets.

He said when drugs bind to the active site of biomolecules, such as enzymes or receptors, they inhibit or modify the function of the biomolecule. For example, a drug binding to an enzyme’s active site inhibits enzyme function as it prevents other substrates from binding.

Abdel-Magid said another approach to drug design is based on secondary binding site effects. Through this approach, small molecule drugs are designed to bind the secondary binding sites, instead of the primary ones, of targeted biomolecules.

These secondary sites are termed allosteric sites, and the drug an allosteric modulator. A successful allosteric modulator binds to the allosteric site, which remotely alters the structure of the primary active site; this interrupts or enhances protein binding to the biomolecule.

Accelerating hit identification

HotSpot Therapeutics said it plans to deploy data from Excelra’s GOSTAR product toward select protein targets to boost its allosteric inhibitor candidate pipeline. 

GOSTAR provides a 360-degree view of more than 8 million small molecules and captures the most up-to-date view of the chemical space with information on chemical structures and their biological properties.

“Partnering with HotSpot Therapeutics allows for an exciting application of hit mining, as it combines AI/ML (artificial intelligence/machine learning models) and structure-based algorithms to accelerate both hit identification and chemical diversification in the field of allostery,” said Norman Azoulay, director of scientific products at Excelra.

“HotSpot’s Smart Allostery drug discovery platform has delivered a pipeline of small molecule inhibitor candidates directed toward difficult to drug or yet to be drugged targets in cancer and autoimmune disease,” said Geraldine Harriman, co-founder and chief scientific officer of HotSpot Therapeutics. 

“Our partnership with Excelra has the potential to expand a portion of HotSpot’s AI-enabled capabilities, allowing for the further advancement of our pipeline of targets with identified natural hotspots, as well as the design of novel allosteric modulators.”

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