Perhexiline induced autophagosome accumulation in the 1�C3 mM range and strong mTORC1 inhibition was seen at 10 mM during 4 h exposure, close to therapeutic concentrations. Niclosamide exerts its antiparasitic activity in the intestinal lumen and was not designed to be absorbed through the intestine. Nevertheless, it shows 10% oral bioavailability and micromolar serum concentrations are achieved after a single oral dose in animals or humans. Intravenous administration of niclosamide to rats gave rise to a peak plasma concentration of 25 mM. Niclosamide very strongly inhibited mTORC1 signaling at concentrations as low as 1 mM. Therefore, therapeutic inhibition of mTORC1 signaling may be achievable using niclosamide or a derivative. Amiodarone can be administered safely for many years with a mean steady state plasma concentration of 2 mM. Peak plasma concentrations can be as high as 60 mM. Amiodarone inhibited mTORC1 signaling at concentrations above 10 mM. Rottlerin is not an approved drug but it shows a low toxicity profile in rodents and it inhibits mTORC1 signaling at 1 mM. The observation that drugs already approved for human use can reversibly inhibit mTORC1 and stimulate autophagy in vitro at concentrations that correspond to or are close to those observed in the circulation during treatment should greatly facilitate the preclinical and clinical testing of mTORC1 inhibition in indications such as tuberous sclerosis, diabetes, cardiovascular disease, protein misfolding diseases and cancer. It is known that SCF is upregulated in inflammatory conditions and therefore presents a potential therapeutic target for the treatment of inflammatory diseases. In addition, gain-of-function mutations in KIT, that is mutations that cause constitutive activation of the tyrosine kinase, have been implicated in a variety of neoplasms including, gastrointestinal stromal tumours, mastocytosis, acute leukaemias, melanomas and other cancers. These mutations are concentrated in the fifth extracellular AZ 960 domain, the juxtamembrane region, and the kinase domain. Also, autocrine or paracrine activation of KIT is thought to be involved in ovarian neoplasms and small-cell lung cancer. In the last decade, several inhibitors of TK have been developed for the treatment of cancer and other diseases. Imatinib mesylate was the first TK inhibitor approved for clinical use. This compound is a potent inhibitor of the PDGF receptor and also BCR-ABL, which causes chronic myelogenous leukaemia. In addition, imatinib inhibits KIT, c-Fms and Syk, and has been approved for the treatment of patients with KIT-positive nonresectable and/or malignant GIST. However, imatinib has a number of short-comings, including the Nutlin-3 Mdm2 inhibitor development of resistance by most if not all patients with subsequent disease progression, as well as resistance of the D816V mutant, which is frequently associated with mastocytosis. Moreover, imatinib may be cardiotoxic due to its inhibition of ABL. Therefore, novel TK inhibitors with improved selectivity are being developed for the treatment of diseases associated with KIT activation. Masitinib, a protein TK developed by AB Science, S.A., is one such new drug. The objective of this preclinical study was to provide a primary characterisation of the in vitro and in vivo activity of masitinib and to compare it against the benchmark protein TK inhibitor imatinib. Masitinib was shown to be inactive against Flt3 and a relatively weak inhibitor of c-Fms, which are two members of the class III RTKs. Masitinib was also inactive against the vascular endothelial growth factor receptor, a RTK often inhibited by KIT inhibitors. In contrast, other KIT inhibitors, including imatinib, dasatinib, and sunitinib, also inhibit several other protein kinases, especially other members of the type III receptor TK family. Thus, masitinib appears to be the most specific inhibitor of KIT.