Switchability and Minimal Effect of Food Effect on Pharmacokinetics of Modified Release Tablet Strengths of Omecamtiv Mecarbil, a Cardiac Myosin Activator

2021 ◽  
Author(s):  
Ashit Trivedi ◽  
Rajneet K. Oberoi ◽  
Mia Mackowski ◽  
Pegah Jafarinasabian ◽  
Hanze Zhang ◽  
...  
Keyword(s):  
Food Effect ◽  
Minimal Effect ◽  
Modified Release ◽  
Cardiac Myosin ◽  
Omecamtiv Mecarbil ◽  
Effect Of Food ◽  
Release Tablet

Polymeric Materials and Formulation Technologies for Modified-Release Tablet Development

2009 ◽  
Vol 9 (13) ◽  
pp. 1504-1517 ◽  
Author(s):  
J. Zarate ◽  
M. Igartua ◽  
R. Hernandez ◽  
J. Pedraz
Keyword(s):  
Polymeric Materials ◽  
Modified Release ◽  
Release Tablet

scholarly journals Cardiac Myosin Activation with Omecamtiv Mecarbil in Systolic Heart Failure

2020 ◽  
Author(s):  
John R. Teerlink ◽  
Rafael Diaz ◽  
G. Michael Felker ◽  
John J.V. McMurray ◽  
Marco Metra ◽  
...  
Keyword(s):  
Heart Failure ◽  
Systolic Heart Failure ◽  
Cardiac Myosin ◽  
Omecamtiv Mecarbil

scholarly journals Perspectives of a myosin motor activator agent with increased selectivity

2018 ◽  
Vol 96 (7) ◽  
pp. 676-680
Author(s):  
Péter Nánási ◽  
István Komáromi ◽  
János Almássy
Keyword(s):  
In Silico ◽  
Clinical Performance ◽  
Ryanodine Receptors ◽  
In Silico Analysis ◽  
Docking Studies ◽  
Cardiac Myosin ◽  
In Silico Docking ◽  
Myosin Motor ◽  
Omecamtiv Mecarbil ◽  
Silico Analysis

Clinical treatment of heart failure is still not fully solved. A novel class of agents, the myosin motor activators, acts directly on cardiac myosin resulting in an increased force generation and prolongation of contraction. Omecamtiv mecarbil, the lead molecule of this group, is now in human phase 3 displaying promising clinical performance. However, omecamtiv mecarbil is not selective to myosin, because it readily binds to and activates cardiac ryanodine receptors (RyR-2), an effect that may cause complications in case of overdose. In this study, in silico analysis was performed to investigate the docking of omecamtiv mecarbil and other structural analogues to cardiac myosin heavy chain and RyR-2 to select the structure that has a higher selectivity to myosin over RyR-2. In silico docking studies revealed that omecamtiv mecarbil has comparable affinity to myosin and RyR-2: the respective Kd values are 0.60 and 0.87 μmol/L. Another compound, CK-1032100, has much lower affinity to RyR-2 than omecamtiv mecarbil, while it still has a moderate affinity to myosin. It was concluded that further research starting from the chemical structure of CK-1032100 may result a better myosin activator burdened probably less by the RyR-2 binding side effect. It also is possible, however, that the selectivity of omecamtiv mecarbil to myosin over RyR-2 cannot be substantially improved, because similar moieties seem to be responsible for the high affinity to both myosin and RyR-2.

Scintigraphic Study to Investigate the Effect of Food on a HPMC Modified Release Formulation of UK-294,315

2009 ◽  
Vol 98 (4) ◽  
pp. 1568-1576 ◽  
Author(s):  
J. Davis ◽  
J. Burton ◽  
A.L. Connor ◽  
R. Macrae ◽  
I.R. Wilding
Keyword(s):  
Modified Release ◽  
Release Formulation ◽  
Effect Of Food ◽  
Scintigraphic Study

Dose-dependent augmentation of cardiac systolic function with the selective cardiac myosin activator, omecamtiv mecarbil: a first-in-man study

The Lancet ◽  
2011 ◽  
Vol 378 (9792) ◽  
pp. 667-675 ◽  
Author(s):  
John R Teerlink ◽  
Cyril P Clarke ◽  
Khalil G Saikali ◽  
Jacqueline H Lee ◽  
Michael M Chen ◽  
...  
Keyword(s):  
Systolic Function ◽  
Cardiac Myosin ◽  
Omecamtiv Mecarbil ◽  
Dose Dependent ◽  
Cardiac Systolic Function
Sign in / Sign up

Export Citation Format

Share Document