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A small-molecule inhibitor of the ubiquitin activating enzyme for cancer treatment
TLDR
TAK-243 treatment caused death of cancer cells and, in primary human xenograft studies, demonstrated antitumor activity at tolerated doses, allowing for interrogation of ubiquitin biology and for assessment of UAE inhibition as a new approach for cancer treatment. Expand
A divergent approach to the myriaporones and tedanolide: Enantioselective preparation of the common intermediate
Abstract The tedanolide and myriaporone classes of natural products represent interesting targets for synthesis because of their structural similarity and biological activity. The asymmetricExpand
(+)-Phorboxazole A synthetic studies. A highly convergent, second generation total synthesis of (+)-phorboxazole A.
TLDR
The second generation total synthesis of the potent antitumor agent (+)-phorboxazole A has been achieved, involving late-stage Stille union of a fully elaborated C(1-28) macrocycle with a C(29-46) side chain. Expand
A second-generation total synthesis of (+)-phorboxazole A.
TLDR
Highlights of the synthetic approach include improved Petasis-Ferrier union/rearrangement conditions on a scale to assemble multigram quantities of the C(11-15) and C(22-26) cis-tetrahydropyrans inscribed with the phorboxazole architecture and a convenient method to prepare E- and Z-vinyl bromides from TMS-protected alkynes. Expand
A divergent approach to the myriaporones and tedanolide: completion of the carbon skeleton of myriaporone 1.
TLDR
A linear but concise synthetic approach toward the structurally related natural products myriaporone and tedanolide is reported, highlighted by a stereoselective homoallenylboration and a regio- and chemoselectives nitrile oxide cycloaddition. Expand
Potency switch between CHK1 and MK2: discovery of imidazo[1,2-a]pyrazine- and imidazo[1,2-c]pyrimidine-based kinase inhibitors.
TLDR
Small structural modifications in both series led to a switch of potency between two kinases involved in mediating cell cycle checkpoint control, CHK1 and MK2. Expand
577 Characterization of the cellular mechanism of action of the first in class investigational inhibitor of the Ubiquitin Activating Enzyme, MLN7243
TLDR
M-COPA could be a promising therapy for treating METaddicted tumors by inhibiting the processing and the transport of MET protein onto the cell surface by reducing phosphorylated forms of MET and its downstream molecules such as Akt and S6. Expand
The Discovery of First-in-Class Inhibitors of the Nedd8-Activating Enzyme (NAE) and the Ubiquitin-Activating Enzyme (UAE)
TLDR
The discovery of first-in-class inhibitors of each of the ubiquitin proteasome enzymes is discussed, including pevonedistat (MLN4924/TAK-924) (NAE) and TAK-243 ( MLN7243) (UAE). Expand
2-Bromoallyl Acetate: A Useful Structural Unit for Sequential Carbon−Carbon Bond Formation
2-Bromoallyl acetate has been shown to be an efficient substrate for Ni(II)/Cr(II)-mediated coupling reactions with a variety of aliphatic and aryl aldehydes. Surprisingly, elimination of acetateExpand
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