Description:
Nilotinib (TasignaTM) is an off-patent, FDA-approved kinase inhibitor. Researchers at UTHealth have discovered it as a promising repurposed drug for muscle wasting treatment at a significantly lower than FDA-approved dose. At 500 nM in vitro, it abrogates muscle catabolism without suppressing myogenesis by selectively inhibiting p38β MAPK, and systemic administration of nilotinib at a low dose of 0.5 mg/kg/day alleviates muscle wasting and prolongs lifespan in tumor-bearing mice. The experimental results highlight the great potential of Nilotinib as a therapeutic for syndromes such as cancer-associated cachexia and sarcopenia.
Background
Cancer has been increasingly recognized as a systemic disease that causes disorders in multiple organs that are not resided by cancer per se. Cachexia, characterized by muscle wasting, is a metabolic syndrome seen in approximately 60% of cancer patients and the direct cause of ~1/3 of cancer-related deaths. Thus, cachexia is a major determinant for cancer patients’ survival. However, there is no established treatment for cancer cachexia due to the poor understanding of its etiology. The unmet medical need for treating cancer cachexia is substantial.
Discovery
Nilotinib (TasignaTM) an off patent, FDA-approved kinase inhibitor has been used by UTHealth investigators at a significantly lower than approved dose as a treatment for muscle wasting. This suggests great potential as a therapeutic for syndromes such as cancer-associated cachexia and sarcopenia.
At 500 nM in vitro, it abrogates muscle catabolism without suppressing myogenesis mediated by p38β MAPK, and systemic administration of nilotinib at a low dose of 0.5 mg/kg/day alleviates muscle wasting and prolongs lifespan in tumor-bearing mice.
Technology Highlights
• Nilotinib, an FDA-approved kinase inhibitor that preferentially binds p38β MAPK (Kd 32 nM) abrogates cancer-induced muscle catabolism at 500 nM in vitro:
• ~20-fold more potent than the p38α/β MAPK inhibitor SB202190
• without suppressing myogenesis mediated by p38a MAPK
• Systemic administration of nilotinib in vivo at a low dose of 0.5 mg/kg/day
alleviates muscle wasting and prolongs lifespan in tumor-bearing mice.
Potential Applications
• Cachexia induced by cancer, sepsis and other inflammatory diseases
• Sarcopeni
Intellectual Property Status
• US Patent filed: US17, 223,597
• Available for licensing
Stage of Development
Preclinical
Associated Publication
About the Principal Investigator
Yi-Ping Li, Ph.D., is a Professor in the Department of Integrative Biology and Pharmacology at McGovern Medical School at UTHealth, Houston Texas. His research interests focus on signaling mechanisms of striated muscle remodeling.
UTHealth Ref. No.: 2020-0026