Abstract: Novel tetrahydroisoquinoline derivative compounds are disclosed herein that may be used as an active ingredient for a pharmaceutical composition, and in particular, for a pharmaceutical composition useful for preventing or treating a disease or condition responsive to modulation of the contractility of the skeletal sarcomere. This may be accomplished, for example, by modulation of the troponin complex of the fast skeletal muscle sarcomere through one or more of fast skeletal myosin, actin, tropomyosin, troponin C, troponin I, and troponin T, and fragments and isoforms thereof. The tetrahydroisoquinoline derivative compounds can thus be used as an agent for preventing or treating 1) neuromuscular disorders, 2) disorders of voluntary muscle, 3) CNS disorders in which muscle weakness, atrophy, and fatigue are prominent symptoms, 4) muscle symptoms stemming from systemic disorders, and 5) dysfunctions of pelvic floor and urethral/anal sphincter muscle.

Abstract: Provided herein are compositions and methods for reducing the decline in vital capacity in a subject by administering to the subject a skeletal muscle troponin activator. Also provided are compositions and methods for reducing respiratory decline in a subject, as measured by slow vital capacity (SVC), by administering to the subject a skeletal muscle troponin activator.

Abstract: Provided are compounds, compositions and methods for improving resistance to skeletal muscle fatigue comprising administering an effective amount of a skeletal muscle troponin activator. Also provided are methods for improving resistance to fatigue, improving physical endurance, or reducing exercise intolerance in a subject suffering from a condition associated with muscle fatigue or weakness, such as heart failure.

Abstract: Provided are compositions and methods for improving diaphragm function in a patient by administering to the patient an effective amount of a skeletal muscle troponin activator or a pharmaceutically acceptable salt thereof.

Abstract: Provided is a method of treating myasthenia gravis in a patient by administering to the patient an effective amount of a skeletal muscle troponin activator, or a pharmaceutically acceptable salt thereof.

Abstract: Provided is a method for treating ALS in a subject, comprising administering to the subject a therapeutically effective amount of riluzole and a therapeutically effective amount of CK-2017357. Also provided are methods of reducing the variability of riluzole exposure (e.g., Cmax and/or AUC24h) in a subject, methods of reducing the variability of riluzole exposure (e.g., Cmax and/or AUC24h) between two or more subjects, methods of decreasing the total daily dose of riluzole in a subject, methods of increasing the half-life of riluzole in a subject, methods for decreasing the frequency of riluzole dosing in the subject, and methods for reducing the incidence and/or severity of adverse events in a subject treated with riluzole.

Abstract: Provided are compounds of Formula I and compounds of Formula II: and pharmaceutically acceptable salts thereof, and methods for their use.

Abstract: Certain substituted sulfonamide derivatives selectively modulate the cardiac sarcomere, for example by potentiating cardiac myosin, and are useful in the treatment of systolic heart failure including congestive heart failure.

Abstract: Certain substituted sulfonamide derivatives selectively modulate the cardiac sarcomere, for example by potentiating cardiac myosin, and are useful in the treatment of systolic heart failure including congestive heart failure.

Abstract: Provided herein are methods of treating lung disease in a subject by administering to the subject a therapeutically effective amount of a mitotic kinesin inhibitor, optionally in combination with another therapy.

Abstract: Provided is a method of treating myasthenia gravis in a patient by administering to the patient an effective amount of a skeletal muscle troponin activator, or a pharmaceutically acceptable salt thereof.

Abstract: Certain substituted sulfonamide derivatives selectively modulate the cardiac sarcomere, for example by potentiating cardiac myosin, and are useful in the treatment of systolic heart failure including congestive heart failure.

Abstract: Provided are methods for treating myasthenia gravis in a patient, comprising administering to the patient an effective amount of at least one chemical entity chosen from compounds of Formula I and compounds of Formula II: and pharmaceutically acceptable salts thereof.

Abstract: Certain substituted sulfonamide derivatives selectively modulate the cardiac sarcomere, for example by potentiating cardiac myosin, and are useful in the treatment of systolic heart failure including congestive heart failure.

Abstract: Methods of identifying skeletal muscle activators are provided. Methods of activating skeletal muscle using skeletal muscle activators are also provided.

Abstract: Certain substituted sulfonamide derivatives selectively modulate the cardiac sarcomere, for example by potentiating cardiac myosin, and are useful in the treatment of systolic heart failure including congestive heart failure.

Abstract: Certain substituted sulfonamide derivatives selectively modulate the cardiac sarcomere, for example by potentiating cardiac myosin, and are useful in the treatment of systolic heart failure including congestive heart failure.

Abstract: Provided is a compound of the following formula: wherein: R3 is an aryl or heteroaryl group, which is optionally substituted with a halogen, lower alkoxy, aryl or heteroaryl group; R4 is halogen; R5 is hydrogen, halogen, hydroxy, or lower alkyl; R6 and R7 are independently selected from hydrogen, halogen, hydroxy, and lower alkyl; and R8 is hydrogen, alkyl, halogen, hydroxy, alkoxy, alkylenedioxy, carboxy, acyloxy, alkoxycarbonyl, alkoxycarbonylamino, alkylcarbonylamino, aminocarbonyl, aminocarbonylamino, cyano, acyl, oxo, nitro, amino, sulfanyl, sulfinyl, sulfonyl, aminosulfonyl, amidino, phenyl, benzyl, heteroaryl, heterocyclyl, aryloxy, arallkoxy, heteroaryloxy, or heteroaralkoxy, wherein the amino(s) in the alkoxycarbonylamino, alkylcarbonylamino, aminocarbonyl, aminocarbonylamino, amino, or aminosulfonyl is optionally substituted with alkyl; or a pharmaceutically acceptable salt thereof.

Abstract: Certain substituted sulfonamide derivatives selectively modulate the cardiac sarcomere, for example by potentiating cardiac myosin, and are useful in the treatment of systolic heart failure including congestive heart failure.

Abstract: Certain substituted sulfonamide derivatives of Formula (I) selectively modulate the cardiac sarcomere, for example by potentiating cardiac myosin, and are useful in the treatment of systolic heart failure including congestive heart failure.