Identification of Four Amoebicidal Nontoxic Compounds by a Molecular Docking Screen of Sterol Δ8-Δ7-Isomerase and Phenotypic Assays.

is a free-living amoeba causing primary amoebic meningoencephalitis, a rapid-onset brain infection in humans with over 97% mortality rate. Despite some progress in the treatment of the disease, there is no single, proven, evidence-based treatment with a high probability of cure. Here we report the chemical library screening and experimental identification of four new compounds with amoebicidal effects against .

Nilotinib, an approved leukemia drug, inhibits smoothened signaling in Hedgehog-dependent medulloblastoma.

Dysregulation of the seven-transmembrane (7TM) receptor Smoothened (SMO) and other components of the Hedgehog (Hh) signaling pathway contributes to the development of cancers including basal cell carcinoma (BCC) and medulloblastoma (MB). However, SMO-specific antagonists produced mixed results in clinical trials, marked by limited efficacy and high rate of acquired resistance in tumors. Here we discovered that Nilotinib, an approved inhibitor of several kinases, possesses an anti-Hh activity, at clinically achievable concentrations, due to direct binding to SMO and inhibition of SMO signaling.

Dexamethasone and Fludrocortisone Inhibit Hedgehog Signaling in Embryonic Cells.

The hedgehog (Hh) pathway plays a central role in the development and repair of our bodies. Therefore, dysregulation of the Hh pathway is responsible for many developmental diseases and cancers. Basal cell carcinoma and medulloblastoma have well-established links to the Hh pathway, as well as many other cancers with Hh-dysregulated subtypes.

The Angiotensin Receptor Blocker Losartan Suppresses Growth of Pulmonary Metastases via AT1R-Independent Inhibition of CCR2 Signaling and Monocyte Recruitment.

Inflammatory monocytes have been shown to play key roles in cancer metastasis through promotion of tumor cell extravasation, growth, and angiogenesis. Monocyte recruitment to metastases is mediated primarily via the CCL2-CCR2 chemotactic axis. Thus, disruption of this axis represents an attractive therapeutic target for the treatment of metastatic disease.