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We investigated <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> the efficacy of ALK4\/5 receptor blockers SB431542 and GW788388 in preventing muscle wasting, and explored synergy with IGF-I analogue LONG R3 (LR3) IGF-I. <jats:italic>In vitro<\/jats:italic>, C2C12 skeletal muscle cells were treated with vehicle, SB431542, GW788388 and LR3 IGF-I. A C26-CD2F1 cachexia model was used to induce cachexia <jats:italic>in vivo<\/jats:italic>. Mice were allocated as non-tumour bearing (NTB) or C26 tumour-bearing (C26 TB) vehicle control, treated with SB431542, LR3 IGF-I, SB431542 and LR3 IGF-I, or GW788388 (intraperitoneally or orally). <jats:italic>In vitro<\/jats:italic>, differentiation index and mean nuclei count increased using SB431542, GW788388, LR3 IGF-I. <jats:italic>In vivo<\/jats:italic>, GW788388 was superior to SB431542 in limiting loss of bodyweight, grip-strength and gastrocnemius weight. and downregulated Atrogin-1 expression comparable to NTB mice. LR3 IGF-I treatment limited loss of muscle mass, but at the expense of accelerated tumour growth. In conclusion, treatment with GW788388 prevented cancer cachexia, and downregulated associated ubiquitin ligase Atrogin-1.<\/jats:p>","DOI":"10.1038\/s41598-019-46178-9","type":"journal-article","created":{"date-parts":[[2019,7,8]],"date-time":"2019-07-08T10:32:20Z","timestamp":1562581940000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Inhibition of activin-like kinase 4\/5 attenuates cancer cachexia associated muscle wasting"],"prefix":"10.1038","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2895-3017","authenticated-orcid":false,"given":"S.","family":"Levolger","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0673-7236","authenticated-orcid":false,"given":"E. A. 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