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This paper reviews materials for thermoelectric waste heat recovery, and discusses selected industrial and distributed waste heat sources as well as recovery methods that are currently applied. Thermoelectric properties, especially electrical conductivity, thermopower, thermal conductivity and the thermoelectric figures of merit, are considered when evaluating thermoelectric materials for waste heat recovery. Alloys and oxides are briefly discussed as materials suitable for medium- and high-grade sources. Electroactive polymers are presented as a new group of materials for low-grade sources. Polyaniline is a particularly fitting polymer for these purposes. We also discuss types of modifiers and modification methods, and their influence on the thermoelectric performance of this class of polymers. [ABSTRACT FROM AUTHOR]

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Graphical abstract Abstract Maternal embryonic leucine zipper kinase (MELK) is involved in several key cellular processes and displays increased levels of expression in numerous cancer classes (colon, breast, brain, ovary, prostate and lung). Although no selective MELK inhibitors have yet been approved, increasing evidence suggest that inhibition of MELK would constitute a promising approach for cancer therapy. A weak high-throughput screening hit (17 , IC 50 ≈ 5 μM) with lead-like properties was optimized for MELK inhibition. The early identification of a plausible binding mode by molecular modeling offered guidance in the choice of modifications towards compound 52 which displayed a 98 nM IC 50. A good selectivity profile was achieved for a representative member of the series (29) in a 486 protein kinase panel. Future elaboration of 52 has the potential to deliver compounds for further development with chemotherapeutic aims. [ABSTRACT FROM AUTHOR]

Fms-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) is one of the most common genetic lesions in acute myeloid leukemia patients (AML). Although FLT3 tyrosine kinase inhibitors initially exhibit clinical activity, resistance to treatment inevitably occurs within months. PIM kinases are thought to be major drivers of the resistance phenotype and their inhibition in relapsed samples restores cell sensitivity to FLT3 inhibitors. Thus, simultaneous PIM and FLT3 inhibition represents a promising strategy in AML therapy. For such reasons, we have developed SEL24-B489 - a potent, dual PIM and FLT3-ITD inhibitor. SEL24-B489 exhibited significantly broader on-target activity in AML cell lines and primary AML blasts than selective FLT3-ITD or PIM inhibitors. SEL24-B489 also demonstrated marked activity in cells bearing FLT3 tyrosine kinase domain (TKD) mutations that lead to FLT3 inhibitor resistance. Moreover, SEL24-B489 inhibited the growth of a broad panel of AML cell lines in xenograft models with a clear pharmacodynamic-pharmacokinetic relationship. Taken together, our data highlight the unique dual activity of the SEL24-B489 that abrogates the activity of signaling circuits involved in proliferation, inhibition of apoptosis and protein translation/metabolism. These results underscore the therapeutic potential of the dual PIM/FLT3-ITD inhibitor for the treatment of AML., Competing Interests: CONFLICTS OF INTEREST W.C., R.W., A.G., M.G., A.S., I.D., M.S., P.G, M.Z., E.G.-W., B.W., M.Ż., E.K., E.W., M.B., M.D., E.M., M.M. and K.B. are or were Selvita employees. G.D. and P.J. are Selvita S.A. stockholders. P.J. is a member of the Scientific Advisory Board at Selvita S.A. P.J and J.T. served as a consultants for Selvita S.A.