Melatonin receptor type 1A (MTR1A) modulates neuronal firing, arterial vasoconstriction, cell proliferation in cancer cells, and reproductive and metabolic functions. MTR1A is a good therapeutic candidate for insomnia, circadian sleep disorders, depression, cardiovascular regulation, cancer, and neurodegenerative diseases.
CALIXAR’s Melatonin receptor type 1A aids in reliable fragment-based drug design (FBDD), structure-based drug discovery (SBDD) and antibody discovery against this specific target.
Unlike Calixar’s MTR1A, other alternative approaches have resulted in a Melatonin receptor that becomes mutated and truncated (96 amino-acids at the C-terminus). This truncation is unable to bind to its natural ligands. In addition, this mutated version becomes locked within an antagonist conformation.
As with all GPCRs, MTR1A is unstable target and inherently difficult to produce natively with conventional approaches. Traditionally, Melatonin receptor type 1A could only be locked in one specific conformation (e.g. antagonist) and were only ever developed in a solution that essentially cannot be pure, nor native (truncated, mutated), without PTMs, and consequently are unstable.
In contrast, CALIXAR’s MTR1A is able to bind to agonists, antagonists, as well as allosteric modulators and preserve their structural and functional integrity. They are purified and stabilized to full length and wild-type (native) proteins.
- Capacity to adapt the buffer condition
- Antibodies (including nanobodies, scaffold proteins, aptamers)
- Small molecules
- 3D Structures (classical X-ray or XFEL, Cryo-EM, NMR)
- Medicine discovery (Screening: HTS, FBDD, SBDD; Hit and lead validation)
- Antibody discovery (Immunization and display technology)
- Clinical stage (drug validation on reliable native MT1)