Cytokinetics 
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  • ||||||||||  tirasemtiv (CK-2017357) / Astellas, Cytokinetics
    Journal:  Measurement of Skeletal Muscle Fiber Contractility with High-Speed Traction Microscopy. (Pubmed Central) -  May 15, 2021   
    Contractile forces of FDB fibers increase in response to caffeine and the troponin-calcium stabilizer tirasemtiv, similar to responses measured in whole muscle...In summary, we present a technically simple high-speed method for measuring contractile forces and cytosolic calcium dynamics of single muscle fibers. We expect that our method will help to reduce preparation time, costs, and the number of sacrificed animals needed for experiments such as drug testing.
  • ||||||||||  aficamten (CK-274) / Cytokinetics
    Enrollment open:  Safety, Tolerability and Pharmacokinetics Study of CK-3773274 (clinicaltrials.gov) -  Apr 27, 2021   
    P1,  N=36, Recruiting, 
    Conclusions The most recent medical therapies provide an additional benefit over NEUi in patients with HFrEF and CKD, which appears to be maximum with SGLT2i. Not yet recruiting --> Recruiting
  • ||||||||||  omecamtiv mecarbil (AMG 423) / Amgen, Servier
    Review, Journal:  Omecamtiv Mecarbil in Chronic Heart Failure With Reduced Ejection Fraction: Rationale and Design of GALACTIC-HF. (Pubmed Central) -  Apr 10, 2021   
    P3
    The GALACTIC-HF trial is the first trial examining whether selectively increasing cardiac contractility in patients with HF with reduced ejection fraction will result in improved clinical outcomes. (Registrational Study With Omecamtiv Mecarbil/AMG 423 to Treat Chronic Heart Failure With Reduced Ejection Fraction [GALACTIC-HF]; NCT02929329).
  • ||||||||||  CK-274 / Cytokinetics, mavacamten (SAR439152) / BMS
    Review, Journal:  Emerging Medical Treatment for Hypertrophic Cardiomyopathy. (Pubmed Central) -  Apr 7, 2021   
    This review summarizes the current treatment modalities and discusses the emerging therapeutical opportunities focusing on the recently developed cardiac myosin ATPase inhibitors Mavacamten and CK-274. Novel surgical and interventional approaches are also discussed.
  • ||||||||||  CK-274 / Cytokinetics
    [VIRTUAL] Discovery of CK-274: A novel, small molecule, cardiac myosin inhibitor for the treatment of hypertrophic cardiomyopathies (HCM) () -  Mar 28, 2021 - Abstract #ACSSp2021ACS-Sp_1377;    
    Cardiac myosin inhibition may be a viable approach to treat the underlying hypercontractility of the cardiac sarcomere in hypertrophic cardiomyopathies. CK-274 is currently being evaluated in phase 2 in a multi-center, randomized, double-blind, placebo-controlled, dose-finding study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of it in adults with symptomatic hypertrophic cardiomyopathy and left ventricular outflow tract obstruction.
  • ||||||||||  Review, Journal:  Small Molecules acting on Myofilaments as Treatments for Heart and Skeletal Muscle Diseases. (Pubmed Central) -  Mar 16, 2021   
    A novel category of small molecules known as "recouplers" was reported to target a phenomenon termed uncoupling commonly found in familial cardiomyopathies but has not progressed beyond preclinical work. In conclusion, the contractile apparatus is a promising target for new drug development.
  • ||||||||||  Farxiga (dapagliflozin) / Ono Pharma, AstraZeneca, Simdax (levosimendan IV) / AbbVie
    Journal:  American Heart Association (AHA) Scientific Sessions 2020 (November 13-17, 2020 - Virtual Meeting). (Pubmed Central) -  Feb 24, 2021   
    AHA 2020 was originally scheduled to be held in Dallas, Texas, but due to public health concerns surrounding the SARS-CoV-2 (COVID-19) crisis, it was instead presented as a virtual summit. The virtual online program included oral, poster and poster discussion presentations, as well as track-based clinical science symposia throughout the conference.
  • ||||||||||  omecamtiv mecarbil (AMG 423) / Amgen, Servier
    Journal:  Phosphorylation of cardiac myosin-binding protein-C contributes to calcium homeostasis. (Pubmed Central) -  Feb 20, 2021   
    These findings indicate a cascade effect whereby cMyBP-C dephosphorylation causes contractile defects, which then lead to calcium-cycling abnormalities, resulting in aftercontractions and increased incidence of cardiac arrhythmias under stress conditions. We conclude that improvement of contractile deficits alone without improving calcium handling may be insufficient for effective management of heart failure.
  • ||||||||||  omecamtiv mecarbil (AMG 423) / Amgen, Servier, Farxiga (dapagliflozin) / Ono Pharma, AstraZeneca
    Review, Journal:  Omecamtiv Mecarbil: A Novel Mechanistic and Therapeutic Approach to Chronic Heart Failure Management. (Pubmed Central) -  Feb 7, 2021   
    Other therapeutic modalities have included loop diuretics, digoxin, the hydralazine-isosorbide dinitrate combination, ivabradine, the inotropes, dobutamine, milrinone, and dopamine...The Global Approach to Lowering Adverse Cardiac Outcomes Through Improving Contractility in Heart Failure (GALACTIC-HF) trial is ongoing and can help provide further clinical data. OM provides a novel mechanism and therapeutic approach to managing patients with HF. Preclinical and clinical data suggest that OM capability can improve cardiac function, decrease ventricular wall stress, reverse ventricular remodeling, and promote sympathetic withdrawal.
  • ||||||||||  omecamtiv mecarbil (AMG 423) / Amgen, Servier, Procoralan (ivabradine) / Amgen, Servier, Ono Pharma
    Journal:  Force and Calcium Transients Analysis in Human Engineered Heart Tissues Reveals Positive Force-Frequency Relation at Physiological Frequency. (Pubmed Central) -  Feb 5, 2021   
    Force-frequency relationship was analyzed in the presence of ivabradine (300 nM), which reduced spontaneous frequency and unmasked a positive correlation of force and CaT at physiological human heart beating frequency with stimulation frequency between 0.75 and 2.5 Hz (force +96%; CaT +102%). This work demonstrates the usefulness of combined force/CaT analysis and demonstrates a positive force-frequency relationship in hiPSC-CM EHTs.
  • ||||||||||  omecamtiv mecarbil (AMG 423) / Amgen, Servier
    Journal:  Myosin from the ventricle is more sensitive to omecamtiv mecarbil than myosin from the atrium. (Pubmed Central) -  Feb 5, 2021   
    However, the interaction characteristics of ventricular myosin with actin were more sensitive to OM than those of atrial myosin. Our results, obtained at the level of isolated proteins, can explain why the impact of OM in therapeutic concentrations on the contractile function of the atrium is less significant as compared to those of the ventricle.
  • ||||||||||  omecamtiv mecarbil (AMG 423) / Amgen, Servier
    Journal:  Cardiac Myosin Activation with Omecamtiv Mecarbil in Systolic Heart Failure. (Pubmed Central) -  Feb 5, 2021   
    P3
    Among patients with heart failure and a reduced ejection, those who received omecamtiv mecarbil had a lower incidence of a composite of a heart-failure event or death from cardiovascular causes than those who received placebo. (Funded by Amgen and others; GALACTIC-HF ClinicalTrials.gov number, NCT02929329; EudraCT number, 2016-002299-28.).
  • ||||||||||  reldesemtiv (CK-2127107) / Astellas, Cytokinetics
    Preclinical, Journal:  Coronary vasculitis induced in mice by the cell wall mannoprotein of Candida krusei. (Pubmed Central) -  Jan 16, 2021   
    Three strains of C. krusei, NBRC1395, NBRC1162, and NBRC10737, were cultured in natural (Y) and chemically defined (C) media and cell wall mannoprotein (MN) fractions were prepared by autoclaving cells (CKY1395MN, CKC1395MN, CKY1162MN, CKC1162MN, CKY10737MN, and CKC10737MN)...MNs also induced coronary vasculitis in C57Bl/6 mice. These results suggest that the MNs of non-albicans Candida, such as C. krusei, induce similar toxicity to those of C. albicans.
  • ||||||||||  omecamtiv mecarbil (AMG 423) / Amgen, Servier
    Enrollment change, Trial withdrawal:  Omecamtiv Mecarbil Post-trial Access Study (clinicaltrials.gov) -  Dec 23, 2020   
    P3,  N=0, Withdrawn, 
    These results suggest that the MNs of non-albicans Candida, such as C. krusei, induce similar toxicity to those of C. albicans. N=900 --> 0 | Not yet recruiting --> Withdrawn