Search Results - "Malik, Fady I"

Mechanistic and structural basis for activation of cardiac myosin force production by omecamtiv mecarbil by Planelles-Herrero, Vicente J., Hartman, James J., Robert-Paganin, Julien, Malik, Fady I., Houdusse, Anne

“…Omecamtiv mecarbil is a selective, small-molecule activator of cardiac myosin that is being developed as a potential treatment for heart failure with reduced…”
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Discovery of Aficamten (CK-274), a Next-Generation Cardiac Myosin Inhibitor for the Treatment of Hypertrophic Cardiomyopathy by Chuang, Chihyuan, Collibee, Scott, Ashcraft, Luke, Wang, Wenyue, Vander Wal, Mark, Wang, Xiaolin, Hwee, Darren T, Wu, Yangsong, Wang, Jingying, Chin, Eva R, Cremin, Peadar, Zamora, Jeanelle, Hartman, James, Schaletzky, Julia, Wehri, Eddie, Robertson, Laura A, Malik, Fady I, Morgan, Bradley P

“…Hypercontractility of the cardiac sarcomere may be essential for the underlying pathological hypertrophy and fibrosis in genetic hypertrophic cardiomyopathies…”
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Cardiac Myosin Activation: A Potential Therapeutic Approach for Systolic Heart Failure by Malik, Fady I., Hartman, James J., Elias, Kathleen A., Morgan, Bradley P., Rodriguez, Hector, Brejc, Katjuša, Anderson, Robert L., Sueoka, Sandra H., Lee, Kenneth H., Finer, Jeffrey T., Sakowicz, Roman, Baliga, Ramesh, Cox, David R., Garard, Marc, Godinez, Guillermo, Kawas, Raja, Kraynack, Erica, Lenzi, David, Lu, Pu Ping, Muci, Alexander, Niu, Congrong, Qian, Xiangping, Pierce, Daniel W., Pokrovskii, Maria, Suehiro, Ion, Sylvester, Sheila, Tochimoto, Todd, Valdez, Corey, Wang, Wenyue, Katori, Tatsuo, Kass, David A., Shen, You-Tang, Vatner, Stephen F., Morgans, David J.

“…Decreased cardiac contractility is a central feature of systolic heart failure. Existing drugs increase cardiac contractility indirectly through signaling…”
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The effects of the cardiac myosin activator, omecamtiv mecarbil, on cardiac function in systolic heart failure: a double-blind, placebo-controlled, crossover, dose-ranging phase 2 trial by Cleland, John GF, Prof, Teerlink, John R, Prof, Senior, Roxy, Prof, Nifontov, Evgeny M, Prof, Mc Murray, John JV, Prof, Lang, Chim C, Prof, Tsyrlin, Vitaly A, Prof, Greenberg, Barry H, Prof, Mayet, Jamil, MD, Francis, Darrel P, MD, Shaburishvili, Tamaz, MD, Monaghan, Mark, PhD, Saltzberg, Mitchell, MD, Neyses, Ludwig, Prof, Wasserman, Scott M, MD, Lee, Jacqueline H, Saikali, Khalil G, PhD, Clarke, Cyril P, MBBS, Goldman, Jonathan H, MD, Wolff, Andrew A, MD, Malik, Fady I, MD

“…Summary Background Many patients with heart failure remain symptomatic and have a poor prognosis despite existing treatments. Decreases in myocardial…”
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Dose-dependent augmentation of cardiac systolic function with the selective cardiac myosin activator, omecamtiv mecarbil: a first-in-man study by Teerlink, John R, Prof, Clarke, Cyril P, MBBS, Saikali, Khalil G, PhD, Lee, Jacqueline H, Chen, Michael M, MS, Escandon, Rafael D, PhD, Elliott, Lyndsey, Bee, Rachel, Habibzadeh, Mohammad Reza, MD, Goldman, Jonathan H, MD, Schiller, Nelson B, Prof, Malik, Fady I, MD, Wolff, Andrew A, MD

“…Summary Background Decreased systolic function is central to the pathogenesis of heart failure in millions of patients worldwide, but mechanism-related adverse…”
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Cardiac myosin activation part 1: From concept to clinic by Malik, Fady I, Morgan, Bradley P

“…Abstract Decreased cardiac contractility is a central feature of systolic heart failure and yet we have no effective drugs to improve cardiac contractility…”
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Cardiac myosin inhibitor, CK-586, minimally reduces systolic function and ameliorates obstruction in feline hypertrophic cardiomyopathy by Rivas, Victor N., Crofton, Amanda E., Jauregui, Carina E., Wouters, Jalena R., Yang, Betty S., Wittenburg, Luke A., Kaplan, Joanna L., Hwee, Darren T., Murphy, Anne N., Morgan, Bradley P., Malik, Fady I., Harris, Samantha P., Stern, Joshua A.

“…Hypertrophic cardiomyopathy (HCM) remains the most common cardiomyopathy in humans and cats with few preclinical pharmacologic interventional studies…”
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Effects of Aficamten on cardiac contractility in a feline translational model of hypertrophic cardiomyopathy by Sharpe, Ashley N., Oldach, Maureen S., Rivas, Victor N., Kaplan, Joanna L., Walker, Ashley L., Kovacs, Samantha L., Hwee, Darren T., Cremin, Peadar, Morgan, Bradley P., Malik, Fady I., Harris, Samantha P., Stern, Joshua A.

“…Hypertrophic cardiomyopathy (HCM) is the most prevalent inherited cardiac disease in humans and cats and lacks efficacious pharmacologic interventions in the…”
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Fast skeletal muscle troponin activator tirasemtiv increases muscle function and performance in the B6SJL-SOD1G93A ALS mouse model by Hwee, Darren T, Kennedy, Adam, Ryans, Julie, Russell, Alan J, Jia, Zhiheng, Hinken, Aaron C, Morgans, David J, Malik, Fady I, Jasper, Jeffrey R

“…Amyotrophic Lateral Sclerosis (ALS) is a motor neuron disease characterized by progressive motor neuron loss resulting in muscle atrophy, declining muscle…”
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Functional Characterization of the Intact Diaphragm in a Nebulin-Based Nemaline Myopathy (NM) Model-Effects of the Fast Skeletal Muscle Troponin Activator tirasemtiv by Lee, Eun-Jeong, Kolb, Justin, Hwee, Darren T, Malik, Fady I, Granzier, Henk L

“…Respiratory failure due to diaphragm dysfunction is considered a main cause of death in nemaline myopathy (NM) and we studied both isometric force and isotonic…”
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Titin-truncating variants in hiPSC cardiomyocytes induce pathogenic proteinopathy and sarcomere defects with preserved core contractile machinery by Huang, Guanyi, Bisaria, Anjali, Wakefield, Devin L., Yamawaki, Tracy M., Luo, Xin, Zhang, Jingli A., Vigneault, Patrick, Wang, Jinghong, Reagan, Jeffrey D., Oliverio, Oliver, Zhou, Hong, Li, Chi-Ming, Vila, Olaia F., Wang, Songli, Malik, Fady I., Hartman, James J., Hale, Christopher M.

“…Titin-truncating variants (TTNtv) are the single largest genetic cause of dilated cardiomyopathy (DCM). In this study we modeled disease phenotypes of A-band…”
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Fast skeletal muscle troponin activation increases force of mouse fast skeletal muscle and ameliorates weakness due to nebulin-deficiency by Lee, Eun-Jeong, De Winter, Josine M, Buck, Danielle, Jasper, Jeffrey R, Malik, Fady I, Labeit, Siegfried, Ottenheijm, Coen A, Granzier, Henk

“…The effect of the fast skeletal muscle troponin activator, CK-2066260, on calcium-induced force development was studied in skinned fast skeletal muscle fibers…”
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Safety and Tolerability of Omecamtiv Mecarbil During Exercise in Patients With Ischemic Cardiomyopathy and Angina by Greenberg, Barry H., MD, Chou, Willis, MD, Saikali, Khalil G., PhD, Escandón, Rafael, PhD, Lee, Jacqueline H., MA, Chen, Michael M., MSc, Treshkur, Tatyana, MD, Megreladze, Irakli, MD, Wasserman, Scott M., MD, Eisenberg, Paul, MD, Malik, Fady I., MD, PhD, Wolff, Andrew A., MD, Shaburishvili, Tamaz, MD

“…Abstract Objectives The goal of this study was to assess the safety and tolerability of omecamtiv mecarbil treatment during symptom-limited exercise in…”
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Discovery of Omecamtiv Mecarbil the First, Selective, Small Molecule Activator of Cardiac Myosin by Morgan, Bradley P, Muci, Alexander, Lu, Pu-Ping, Qian, Xiangping, Tochimoto, Todd, Smith, Whitney W, Garard, Marc, Kraynack, Erica, Collibee, Scott, Suehiro, Ion, Tomasi, Adam, Valdez, S. Corey, Wang, Wenyue, Jiang, Hong, Hartman, James, Rodriguez, Hector M, Kawas, Raja, Sylvester, Sheila, Elias, Kathleen A, Godinez, Guillermo, Lee, Kenneth, Anderson, Robert, Sueoka, Sandra, Xu, Donghong, Wang, Zhengping, Djordjevic, Nebojsa, Malik, Fady I, Morgans, David J

“…We report the design, synthesis, and optimization of the first, selective activators of cardiac myosin. Starting with a poorly soluble, nitro-aromatic hit…”
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Phase 2 Study of Aficamten in Patients With Obstructive Hypertrophic Cardiomyopathy by Maron, Martin S., Masri, Ahmad, Choudhury, Lubna, Olivotto, Iacopo, Saberi, Sara, Wang, Andrew, Garcia-Pavia, Pablo, Lakdawala, Neal K., Nagueh, Sherif F., Rader, Florian, Tower-Rader, Albree, Turer, Aslan T., Coats, Caroline, Fifer, Michael A., Owens, Anjali, Solomon, Scott D., Watkins, Hugh, Barriales-Villa, Roberto, Kramer, Christopher M., Wong, Timothy C., Paige, Sharon L., Heitner, Stephen B., Kupfer, Stuart, Malik, Fady I., Meng, Lisa, Wohltman, Amy, Abraham, Theodore

“…Left ventricular outflow tract (LVOT) obstruction is a major determinant of heart failure symptoms in obstructive hypertrophic cardiomyopathy (oHCM)…”
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Effect of Ejection Fraction on Clinical Outcomes in Patients Treated With Omecamtiv Mecarbil in GALACTIC-HF by Teerlink, John R., Diaz, Rafael, Felker, G. Michael, McMurray, John J.V., Metra, Marco, Solomon, Scott D., Biering-Sørensen, Tor, Böhm, Michael, Bonderman, Diana, Fang, James C., Lanfear, David E., Lund, Mayanna, Momomura, Shin-ichi, O'Meara, Eileen, Ponikowski, Piotr, Spinar, Jindrich, Flores-Arredondo, Jose H., Claggett, Brian L., Heitner, Stephen B., Kupfer, Stuart, Abbasi, Siddique A., Malik, Fady I.

“…In GALACTIC-HF (Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure) (n = 8,256), the cardiac myosin…”
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Inhibition of smooth muscle myosin as a novel therapeutic target for hypertension by Zhao, Xin, Ho, David, Abarzúa, Patricio, Dhar, Sunil K, Wang, Xi, Jia, Zhiheng, Pannirselvam, Malar, Morgans, David J, Malik, Fady I, Vatner, Stephen F

“…We examined a novel therapeutic approach for hypertension, a small-molecule direct inhibitor of smooth muscle myosin, CK-2018448 (CK-448), which is an…”
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Omecamtiv Mecarbil in Chronic Heart Failure With Reduced Ejection Fraction: Rationale and Design of GALACTIC-HF by Teerlink, John R, Diaz, Rafael, Felker, G Michael, McMurray, John J V, Metra, Marco, Solomon, Scott D, Legg, Jason C, Büchele, Gustavo, Varin, Claire, Kurtz, Christopher E, Malik, Fady I, Honarpour, Narimon

“…A central factor in the pathogenesis of heart failure (HF) with reduced ejection fraction is the initial decrease in systolic function. Prior attempts at…”
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CK‐2127107 amplifies skeletal muscle response to nerve activation in humans by Andrews, Jinsy A., Miller, Timothy M., Vijayakumar, Vipin, Stoltz, Randall, James, Joyce K., Meng, Lisa, Wolff, Andrew A., Malik, Fady I.

“…ABSTRACT Introduction Three studies evaluated safety, tolerability, pharmacokinetics, and pharmacodynamics of CK‐2127107 (CK‐107), a next‐generation fast…”
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Smooth muscle myosin inhibition: a novel therapeutic approach for pulmonary hypertension by Ho, David, Chen, Li, Zhao, Xin, Durham, Nicquanna, Pannirselvam, Malar, Vatner, Dorothy E, Morgans, David J, Malik, Fady I, Vatner, Stephen F, Shen, You-Tang

“…Pulmonary hypertension remains a major clinical problem despite current therapies. In this study, we examine for the first time a novel pharmacological target,…”
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