Systematic Drug Discovery Platform Inspired by Proteins

Innovation: Industry

HotSpot Therapeutics

2017

Image: Paweł Czerwiński / Unsplash / CC BY SA - Creative Commons Attribution + ShareAlike

Maintain Homeostasis

When a living system is in homeostasis, it means that internal conditions are stable and relatively constant. For example, a human’s internal temperature is approximately 37 degrees Celsius (98.6 degrees Fahrenheit) unless there’s an illness. The human body maintains this temperature despite external ambient temperature. However, as with all physiological processes, maintaining homeostasis requires communication and coordination. So living systems have ways to detect changes from the norm, mechanisms to cause an adjustment, and negative feedback connections between the two. A desert lizard called the Gila monster offers a good example of maintaining homeostasis. The lizard goes from eating large meals to fasting for extended time periods. To maintain its blood sugar levels at a steady level, when food is scarce, its endocrine system releases a hormone that raises its blood sugar levels.

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Sense Disease in a Living System

Living systems that can detect diseases within themselves, or within other living systems, can direct resources toward curing those diseases or preventing their spread. This type of sensing environmental cues is not well known, probably because of the difficulty studying disease detection, including the difficulty in providing scientific proof. However, there are a few known examples, such aschimpanzees that detect illness in themselves and self-medicate through eating plants with medicinal benefits.

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SpotFinder from HotSpot Therapeutics uses an allosteric approach that identifies new binding sites for disease-fighting drugs.

Benefits

Reduced side effects
Increased drug targets

Applications

Pharmaceuticals
Drug discovery

UN Sustainable Development Goals Addressed

Goal 3: Good Health & Wellbeing

The Challenge

A drug does its job by binding to a to initiate or block activity. Typical drug discovery focuses on finding compounds that target the ‘active site’— a small location where a protein binds to another molecule and causes a chemical reaction. However, drugs that bind active sites can oftentimes lead to side effects caused by accidentally binding to the wrong site, or blocking natural molecules that use the same site.

Innovation Details

SpotFinder™ is a drug discovery platform that identifies new binding sites, known as regulatory hotspots, for disease-fighting drugs. Unlike active sites, regulatory hotspots are more difficult to find and require a deep understanding of protein structure and function. SpotFinder™ takes a systems-wide view across all proteins to uncover previously unknown regulatory hotspots. The platform identifies drugs and regulatory hotspots across multiple classes of proteins, and has been able to identify protein classes that were previously considered undruggable.

Biological Model

Drugs selectively correct for chemical imbalances and dysregulation to restore health and proper functioning by precisely altering the sites that control the function of a protein. For example, when an oxygen molecule binds to a non-active site on hemoglobin, it causes other locations of the protein to become more receptive to additional oxygen molecules, making the hemoglobin able to deliver more oxygen to the body.

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