CK-586 (cardiac myosin inhibitor)

Cytokinetics

Hello everyone! It’s been a while but I’m back after finishing a grueling first year in med school. After being bombarded with exams every week, I’m happy to report that I survived (hooray)!

Today’s post is on how I figured out the structure of CK-586, a cardiac myosin inhibitor by Cytokinetics ( CYTK 0.00%↑) in phase 1 trials for hypertrophic cardiomyopathy/heart failure with preserved ejection fraction (NCT05877053). Funny enough, I ended my first year with the cardio block, so navigating the data on this compound brought back PTSD fond memories.

A housekeeping note: going forward, I’ll be keeping the 1 week paywall for free subscribers for the structure. After 1 week, I’ll reveal the structure as I’ve done but the process will be kept behind paywall.

Why have I chosen to do this? Well, it often takes me several hours to compile the data and then put it all together in a presentable format. I’m strapped for time these days, so I think it’s only reasonable to keep the process behind paywall. I hope you all can understand.

Without further ado…

CK-586 is a cardiac myosin inhibitor that is being developed by Cytokinetics (CYTK 0.00%↑) for hypertrophic cardiomyopathy. It is currently in phase 1 trials (NCT05877053).

HCM involves hypertrophy of the ventricles or intraventracular septum of the heart an results in heart failure with preserved ejection fraction (HFpEF). A subset of HCM, called hypertrophic obstructive cardiomyopathy (HOCM), is the most common inherited cardiomyopathy, affecting 1:250-500 people, and is a major contributor to sudden death in young people.

HCM can be caused by mutations in cardiac myosin genes that lead to hypercontractility of the sarcomere. This leads to pathololgicl hypertrophy and fibrosis.

So the thought behind a cardiac myosin inhibitor like CK-586 is that inhibition of cardiac myosin may be able to inhibit hypercontractility in HCM/HFpEF.