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Corrigendum Open Access | 10.1172/jci.insight.214144

Corrigendum to Mechanistic diversity within RLC-dependent myosin ATPase inhibitors differentiates EDG-7500, a diastolic-selective cardiac sarcomere modulator

Craig A. Emter, Marcus Henze, Mike DuVall, Sarah Lehman, Lindsey Lee, Ben Barthel, Natalie A. Hawryluk, Molly Madden, Yangsong Wu, Amy Perry, Martin Beyer, Eric Wei, Cassady Rupert, Steve Roof, Angela Peter, Emily DiNatale, Sara Cantrell, Jessica Tolley, Stephen Schlachter, Jolanda van der Velden, Michelle Michels, Christine Seidman, Weikang Ma, Leslie Leinwand, Stuart Campbell, Julien Ochala, David Bluemke, Darla Tharp, Jonathan Seidman, Carlos L. del Rio, Marc Semigran, Marc Evanchik, Kevin Koch, and Alan Russell

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Published November 9, 2026 - More info

Published in Volume 11, Issue 21 on November 9, 2026
JCI Insight. 2026;11(21):e214144. https://doi.org/10.1172/jci.insight.214144.
© 2026 Emter et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published November 9, 2026 - Version history
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Mechanistic diversity within RLC-dependent myosin ATPase inhibitors differentiates EDG-7500, a diastolic-selective cardiac sarcomere modulator
Craig A. Emter, Marcus Henze, Mike DuVall, Sarah Lehman, Lindsey Lee, Ben Barthel, Natalie A. Hawryluk, Molly Madden, Yangsong Wu, Amy Perry, Martin Beyer, Eric Wei, Cassady Rupert, Steve Roof, Angela Peter, Breanne L. Newell-Stamper, Ying Qian, Emily DiNatale, Sara Cantrell, Jessica Tolley, Stephen Schlachter, Jolanda van der Velden, Michelle Michels, Christine Seidman, Weikang Ma, Leslie Leinwand, Stuart Campbell, Julien Ochala, David Bluemke, Darla Tharp, Jonathan Seidman, Carlos L. del Rio, Marc Semigran, Marc Evanchik, Kevin Koch, Alan Russell
Craig A. Emter, Marcus Henze, Mike DuVall, Sarah Lehman, Lindsey Lee, Ben Barthel, Natalie A. Hawryluk, Molly Madden, Yangsong Wu, Amy Perry, Martin Beyer, Eric Wei, Cassady Rupert, Steve Roof, Angela Peter, Breanne L. Newell-Stamper, Ying Qian, Emily DiNatale, Sara Cantrell, Jessica Tolley, Stephen Schlachter, Jolanda van der Velden, Michelle Michels, Christine Seidman, Weikang Ma, Leslie Leinwand, Stuart Campbell, Julien Ochala, David Bluemke, Darla Tharp, Jonathan Seidman, Carlos L. del Rio, Marc Semigran, Marc Evanchik, Kevin Koch, Alan Russell
The cardiac sarcomere modulator EDG-7500 demonstrates diastolic efficacy without systolic impairment differentiating it amongst other RLC-modulators and traditional cardiac myosin inhibitors, offering a novel therapeutic approach for treating both obstructive and nonobstructive HCM and potentially optimizing functional benefit.
Research Article Cardiology Muscle biology

Mechanistic diversity within RLC-dependent myosin ATPase inhibitors differentiates EDG-7500, a diastolic-selective cardiac sarcomere modulator

Abstract

Small molecules that modulate myofibril ATPase activity via the myosin regulatory light chain (RLC) display a broad spectrum of activity in their ability to enhance relaxation and slow contraction. EDG-7500 exhibits features consistent with a ‘diastolic-selective’ cardiac sarcomere modulator (d-CSM), and its ability to treat HCM was explored in engineered human tissue (EHT), human HCM cardiac strips, and an R403Q mutation swine model. In fibers, EDG-7500 preferentially inhibited myofibril ATPase activity and force at diastolic calcium levels, retained length-dependent force activation, accelerated relaxation, and exhibited a shallow, self-limiting inhibitory-exposure response to LV fractional shortening. Compared to CMIs, EDG-7500 moved myosin heads towards the thin filament and accelerated relaxation without decreasing force in mutated EHTs (R403Q). In human HCM cardiac strips, EDG-7500 did not alter myosin SRX state, but decreased Ca2+-sensitivity of force independent of mutation. In R403Q swine, chronic EDG-7500 normalized LV filling pressure and prevented pathological cardiac remodeling while preserving normal systolic function and cardiac reserve. EDG-7500 differentiates itself from CMIs by uniquely targeting both phases of the cardiac cycle, improving ventricular relaxation while preserving systolic function. This suggests optimal diastolic efficacy can be reached without balancing systolic impairment.

Authors

Craig A. Emter, Marcus Henze, Mike DuVall, Sarah Lehman, Lindsey Lee, Ben Barthel, Natalie A. Hawryluk, Molly Madden, Yangsong Wu, Amy Perry, Martin Beyer, Eric Wei, Cassady Rupert, Steve Roof, Angela Peter, Breanne L. Newell-Stamper, Ying Qian, Emily DiNatale, Sara Cantrell, Jessica Tolley, Stephen Schlachter, Jolanda van der Velden, Michelle Michels, Christine Seidman, Weikang Ma, Leslie Leinwand, Stuart Campbell, Julien Ochala, David Bluemke, Darla Tharp, Jonathan Seidman, Carlos L. del Rio, Marc Semigran, Marc Evanchik, Kevin Koch, Alan Russell

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Original citation: JCI Insight. 2026;11(18):e203086. https://doi.org/10.1172/jci.insight.203086

Citation for this corrigendum: JCI Insight. 2026;11(21):e214144. https://doi.org/10.1172/jci.insight.214144

After publication, the authors became aware that Breanne L. Newell-Stamper and Ying Qian were inadvertently omitted from the author list. The author list has been updated in the HTML and PDF versions.

The authors regret the error.

Footnotes

See the related article at Mechanistic diversity within RLC-dependent myosin ATPase inhibitors differentiates EDG-7500, a diastolic-selective cardiac sarcomere modulator.

Version history
  • Version 1 (November 9, 2026): Electronic publication
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