Drug Discovery for Endocrine Channelopathies

As the number of people exhibiting risk factors for endocrine channelopathies continues to increase, drug discovery for these diseases remains an important area of focus within the scientific community. Researchers at Creative Bioarray focus on the molecular biology of endocrine channelopathies to help clients develop new strategies to treat these diseases, accelerating the translation of basic research into clinical reality.

Introduction

Ion channels are involved in multiple key physiological processes in endocrine cells, including hormone secretion, Ca²⁺ signaling, cell motility and growth, osmotic pressure regulation, transepithelial transport, chemotransduction, regulation of cellular ion content, and mechanotransduction and acidification. Dysfunction of these ion channels often causes endocrine dysregulation and contributes to a variety of endocrine disorders, such as persistent hyperinsulinemic hypoglycemia of infancy, neonatal diabetes, hypomagnesemia with secondary hypocalcemia, and thyrotoxic hypokalemic periodic paralysis.

It is likely that some ion channels in endocrine cells are multifunctional and serve many different physiological purposes, mainly involving metabolic regulation. Given the important role of ion channels in the development and progression of endocrine diseases, scientists are increasingly interested in understanding the diversity of ion channels in endocrine cells. Understanding the unique biological properties of excitable endocrine cells facilitates the development and formulation of efficient therapeutic strategies for endocrine channelopathies.

Fig. 1 Schematic illustration of an endocrine cell action potential. (Rolim, 2010)

Drug Development for Endocrine Channelopathies

Researchers at Creative Bioarray focus on the biophysical properties of endocrine cells and the physiopathological mechanisms of endocrine channelopathies to help clients develop treatments for endocrine diseases mediated by ion channel defects. Our strong knowledge of disease biology, innovative target identification and validation services, and sophisticated pharmacology models allow us to provide you with high-quality drug development services. Our services include, but are not limited to:

• Drug discovery for familial congenital hyperinsulinemia
  The ATP-sensitive K⁺ channel (KATP) complex has been shown to be involved in genetic disorders related to insulin/glucose metabolism. We focused on developing hyperglycemic drugs that open KATP channels to reduce insulin release in congenital hyperinsulinemia.
• Drug discovery for neonatal diabetes mellitus and DEND syndrome
  We focused on developing hypoglycemic drugs that block KATP channels to increase insulin levels in neonatal diabetic patients.
• Drug discovery for osteopetrosis
  CLCN7 (ClC-7) has been shown to be involved in the development of osteosclerosis. Treatment is aimed at increasing bone resorption. We are working to develop selective compounds that can open/activate ClC-7 or slow the accelerated activation of certain ClC-7 mutants.

Advantages

• Extensive standard and specialty laboratory services
• Comprehensive testing programs and equipment
• Exceptional support of the entire drug discovery process

Creative Bioarray provides full-service support throughout the drug discovery and development process for endocrine channelopathies. We continually strive to develop comprehensive solutions to expand our support for your work. If you need our scientific services and technical support, please contact us for more details.

Reference

1. Rolim, A. L. R.; et al. Ion channelopathies in endocrinology: recent genetic findings and pathophysiological insights. Arquivos Brasileiros de Endocrinologia & Metabologia, 2010, 54: 673-681.