LRRC8 proteins and protein complexes and methods for identification of channel modulators

Simple SummaryContent extracted from patent full text and abstract with AI.

This invention provides a method using LRRC8 proteins and their complexes, specifically heteromers containing LRRC8A and at least one of LRRC8B, LRRC8C, LRRC8D, or LRRC8E, to identify substances (modulators) that can activate or inhibit volume-regulated anion channels (VRACs). It also provides kits and isolated protein complexes for use in such methods. The identification of modulators is based on the ability of candidate substances to change the transport of marker molecules (like ions, amino acids, drugs) through these channels in cell membranes. This allows discovery of compounds that can selectively influence these channels, which play critical roles in cell volume regulation, cell proliferation, migration, and response to stress, with implications for treating diseases such as cancer, diabetes, and infectious diseases.

Use CasesContent extracted from patent full text and abstract with AI.

• Screening for new drugs that specifically activate or inhibit VRAC channels to treat cancers, where cell volume regulation affects proliferation, apoptosis, and metastasis.
• Identifying compounds that enhance the uptake of antibiotics or cytotoxic drugs into cells, potentially overcoming drug resistance in cancer or infectious diseases.
• Discovering modulators for VRAC channels relevant in neurological diseases (e.g., stroke, brain edema) by targeting specific LRRC8 subunit combinations found in neurons or glial cells.
• Developing research tools to study cell volume control mechanisms, osmotic balance, and physiological processes related to ion and osmolyte transport.
• Screening tissue- or cell-type-specific VRAC modulators to tailor therapies that minimize side effects by targeting only relevant tissue.
• Enabling studies of insulin release modulation via pancreatic beta-cell VRAC activity for diabetes treatment strategies.

BenefitsContent extracted from patent full text and abstract with AI.

• Provides the first robust molecular identification of VRAC channel complex components (LRRC8A-E), resolving a longstanding scientific mystery.
• Enables high-throughput, specific screening for small molecules and biologics that modulate VRAC channels, streamlining the drug discovery process for several critical diseases.
• Allows development of tissue-specific modulators by using defined LRRC8 subunit compositions, reducing off-target and side effects.
• Supports personalized medicine approaches by matching VRAC modulator activity to the unique LRRC8 profiles in specific disease tissues or cell types.
• Improves understanding of and ability to intervene in cell volume regulation, with impact on fundamental cell biology research and various clinical applications.
• The provided kits and methods are versatile, adaptable for research, pharmaceutical development, and diagnostic uses.

Technical Classifications (CPCs)

Inventors & Applicants

Patent Abstract

The invention relates to a method for the identification of a channel modulator, such as an agonist or antagonist, that interacts with one or more or LRRC8A, LRRC8B, LRRC8C, LRRC8D and/or LRRC8E and/or protein complexes thereof. The invention further relates to an isolated heteromeric protein complex comprising one or more or LRRC8A, LRRC8B, LRRC8C, LRRC8D and/or LRRC8E for use in such methods, in addition to kits suitable for carrying out such methods. The invention therefore relate preferably to the use of LRRC8 proteins and complexes thereof for the identification of VRAC (VSOAC) modulators.