Calcium Channel Blocker Development for Stroke

Calcium performs normal physiological functions as a membrane stabilizer, metabolic regulator and second messenger. However, it can also be involved in hypoxia and toxic cell death. In ischemic stroke, the influx of calcium into neurons represents the "ultimate common pathway". A pathological increase in cytoplasmic calcium concentration leads to cell damage and death by causing increased lipolysis and protein hydrolysis, energy dissipation, protein kinase activation, and altered gene expression. Calcium antagonist therapy may offer a way to halt and possibly prevent brain tissue destruction in stroke patients.

Fig. 1. Calcium influx as an emerging treatment target for ischemic stroke. (Kearns et al., 2022)

Our Calcium Channel Blocker Development Services

Ace Therapeutics is a leading global provider of stroke drug development services. Our extensive experience and expertise in this field can help clients study the Ca²⁺ influx mechanism in brain cells (especially microglia) under ischemic conditions. We also help clients develop calcium channel blockers for the treatment of stroke. We work closely with pharmaceutical companies, academic institutions, and research organizations to understand their specific needs and goals.

From calcium channel blocker discovery to preclinical evaluation, you can rely on our project management team to provide you with a reliable, consistent and stress-free experience.

Design and Optimization of Calcium Channel-Targeted Compounds

Using advanced techniques such as crystallography and surface plasmon resonance (SPR) fragment screening, we identify calcium channel targets and screen compounds to discover compounds that interact with these targets. In addition, we perform pharmaceutical and computational chemistry screening and analysis to help clients rapidly screen compounds that can target the following calcium channels.

• Targeting cell surface purinergic receptors
• Targeting calcium release-activated calcium (CRAC) channels
• Targeting calcium-permeable acid-sensing ion channels

We provide pharmaceutical and computational chemistry techniques to optimize the properties of these calcium channel blockers, involving iterative design, synthesis and testing to improve potency, selectivity, and ability to cross the blood-brain barrier (BBB).

Preclinical Evaluation of Calcium Channel Blockers

We conduct rigorous preclinical testing of calcium channel blockers to evaluate their safety and efficacy in animal and in vitro models of stroke. Through careful experimental design and data analysis, we can assess the ability of calcium channel blockers to reduce neuronal damage, improve functional outcomes, and minimize adverse effects.

• In vitro studies involve the use of cell culture and neuronal assays to investigate the effects of compounds on calcium channel function, neuronal excitability, and cell viability under ischemic conditions.
• By administering calcium channel inhibitors in animal stroke models, we can assess their effects on cerebral blood flow, infarct size, neurological deficits, and other relevant parameters.

Ace Therapeutics is your trusted partner for providing comprehensive services in the development of calcium channel blockers for the treatment of stroke. If you are interested in our services, please do not hesitate to contact us!

1. Kearns, K. N., et al. (2022). Microglia modulate cortical spreading depolarizations after ischemic stroke: a narrative review. Neurocritical care, 37(Suppl 1), 133-138.