MCL1 is an anti-apoptotic protein that prevents cancer cell death and promotes abberant cancel cell survival. Overexpression of this protein is linked to poor prognosis and therapeutuc resitance. Therefore, inhibition of this protein is an interesting target for cancer therapies.
Serveral MCL1 inhibitors are currently under investigation in early clinical trials. However, the relevant role of MCL1 in cardiac function can compromised the safety of the drugs. To illustrate, dose escalation of MCL1 inhibitors often leads to cardiotoxicity. This significantly slows down clinical development of MCL1 inhibitors. Predicting cardiotoxicity earlier in the drug development process would safe important resources and time.
In this study, Trueline Therapeutics partnered with Ncardia to assess dose tolerance and cardiotoxicity of a new MCL1 inhibitor in a relevant iPSC-derived cardiac model. The results indicate that the MCL1 inhibitor TTX-810 has a broad anti-cancer potential of targeting MCL1 with no effects on healthy cardiomyocytes. It has strong anti-tumor efficacy while there is no effect on cardiomyocytes. TTX-180 is now in preparation for clinical development.