Certain substituted urea derivatives modulate diskeletal myosin, skeletal actin, skeletal tropomyosin, skeletal troponin C, skeletal troponin I, skeletal troponin T, and skeletal muscle, including fragments and isoforms thereof, as well as the skeletal sarcomere, and are useful in the treatment of obesity, sarcopenia, wasting syndrome, frailty, muscle spasm, cachexia, neuromuscular diseases (e.g., amyotrophic lateral sclerosis, spinal muscular atrophy, familial or acquired myopathies or muscular dystrophies), post-surgical and post-traumatic muscle weakness, and other conditions.