the subject of intense studies in the recent years in order to restore regenerative potential . However, a major limitation of cell-based strategies is the poor survival of transplanted cells within skeletal muscles . In vivo, most transplanted myoblasts die in the first few days following transplantation, preventing their participation to tissue regeneration. This is at least in part due to the hypoxic environment, as large number of cells transplanted into a solid organ form a mass in which blood vessels are not present, hence limiting the oxygen supply . Hypoxia activates a complex set of pathways, supporting the development of a system-level therapeutic approach. Although cellular hypoxia promotes cell death, the lack of oxygen supply also activates several adaptive pathways to promote survival. These include a order Tyr-Gly-Gly-Phe-Met-OH switch to anaerobic metabolism by enhancing glycolysis and inhibiting the Krebs cycle, a switch from anabolic to catabolic pathways to limit energy expenditures and the activation of autophagy, a key adaptive response to cellular stress . Approaches targeting angiogenesis and stress proteins have been reported to improve myoblast survival upon transplantation. These factors include Hypoxia Inducible Factor 1 alpha , Vascular Endothelial Growth Factor , and Heat Shock Proteins . The identification of drugs that can confer hypoxia resistance would improve the outcome of myoblast replacement therapy, possibly in combination with these approaches. Fmoc-Val-Cit-PAB-MMAE Protein kinases are the key regulators of numerous cellular signaling pathways and multiple kinase pathways are involved in the responses to hypoxic stresses. Thus, simultaneously targeting several kinases involved in the hypoxia-induced cellular death processes might help to protect myoblasts from hypoxia. In this study, we screened for kinase inhibitors that affect hypoxia-resistance in vitro. Several candidate kinase inhibitors were identified with potent effects on primary myoblast survival under hypoxia. Fully factorial analysis uncovered kinase inhibitor combinations able to both additively and synergistically improve myoblast survival. Using a pathway analysis and a novel statistical method developed
