Andreas Sellmer

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FLT3 receptor tyrosine kinase is aberrantly active in many cases of acute myeloid leukemia (AML). Recently, bis(1H-indol-2-yl)methanones were found to inhibit FLT3 and PDGFR kinases. To optimize FLT3 activity and selectivity, 35 novel derivatives were synthesized and tested for inhibition of FLT3 and PDGFR autophosphorylation. The most potent FLT3(More)
Acetylation and deacetylation cycles regulate crucial biological processes. The enzymes deacetylating lysine residues are termed histone deacetylases (HDACs). Eighteen deacetylases have been isolated from mammalian cells. There is an intense search underway for individual functions of these enzymes and for selective histone deacetylase inhibitors (HDACi).(More)
Synthesis and cytotoxic activity in the submicromolar range of a series of [4-(imidazol-1-yl)thiazol-2-yl]phenylamines are described. Cell cycle dependent cytotoxicity on RKO human colon carcinoma cells with inducible expression of p27(kip1) and the influence on microtubule formation were investigated. Considering the significant correlation between the(More)
A series of bis(benzo[b]furan-2-yl)methanones was synthesized and tested for inhibition of FLT3 and PDGFR autophosphorylation. Mostly, C-5 substitution leads to PDGFR selectivity, which was strongest in the case of the 5,5'-dimethoxy derivative. The 5,5'-diamino and the 6,6'-dihydroxy compounds are more active at FLT3. At both kinases, the potency of the(More)
A number of lapacho compounds, representing the most common constituents of the inner bark of Tabebuia impetiginosa, together with some synthetic analogues, were evaluated in vitro against the growth of the human keratinocyte cell line HaCaT. With an IC(50) value of 0.7 microM, beta-lapachone (4) displayed activity comparable to that of the antipsoriatic(More)
The essential role of microtubules in mitosis makes them a major target of compounds useful for cancer therapy. In our search for potent antitumor agents, a novel series of 2-anilino-4-amino-5-aroylthiazoles was synthesized and evaluated for antiproliferative activity, inhibition of tubulin polymerization, and cell cycle effects. SAR was elucidated with(More)
Reversible lysine-specific acetylation has been described as an important posttranslational modification, regulating chromatin structure and transcriptional activity in the case of core histone proteins. Histone deacetylases (HDAC) are considered as a promising target for anticancer drug development, with 2a as pan-HDAC inhibitor approved for cutanous(More)
Inhibitors of histone deacetylases are a new class of cancer therapeutics with possibly broad applicability. Combinations of HDAC inhibitors with the kinase inhibitor 1 (Imatinib) in recent studies showed additive and synergistic effects. Here we present a new concept by combining inhibition of protein kinases and HDACs, two independent pharmacological(More)
Synthesis and cytotoxic activity of a series of 2-acyl-1H-indole-4,7-diones on human cancer cell lines are described. Due to close structural relationship to 2-acylindoles, potent inhibitors of tubulin polymerization, the mode of action of these novel compounds has been investigated. Cytotoxicity, the influence on tubulin polymerization, and cell cycle(More)
The novel lead bis(1H-2-indolyl)methanone inhibits autophosphorylation of platelet-derived growth factor (PDGF) receptor tyrosine kinase in intact cells. Various substituents in the 5- or 6-position of one indole ring increase or preserve potency, whereas most modifications of the ring structures and of the methanone group as well as substitution at both(More)