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NF-kappa B as a therapeutic target in multiple myeloma.
It is demonstrated that specific targeting of NF-kappaB can overcome the growth and survival advantage conferred both by tumor cell binding to BMSCs and cytokine secretion in the BM milieu. Expand
NF-κB as a Therapeutic Target in Multiple Myeloma*
We have shown that thalidomide (Thal) and its immunomodulatory derivatives (IMiDs), proteasome inhibitor PS-341, and As2O3 act directly on multiple myeloma (MM) cells and in the bone marrow (BM)Expand
Discovery of a potent and orally active hedgehog pathway antagonist (IPI-926).
IPI-926 (compound 28), a novel semisynthetic cyclopamine analogue with substantially improved pharmaceutical properties and potency and a favorable pharmacokinetic profile relative tocyclopamine and compound 2, is discovered. Expand
Novel IKK inhibitors: beta-carbolines.
Optimization of this beta-carboline natural product derivative resulted in a novel class of selective IKK inhibitors with IC(50)s in the nanomolar range and it is shown that one of these beta- carboline analogues inhibits the phosphorylation of IkappaBalpha and subsequent activation of NF-kappaB in whole cells, as well as blocking TNF-alpha release in LPS-challenged mice. Expand
Novel IKK inhibitors: β-carbolines
Abstract Inhibitors of IκB kinase (IKK) have long been sought as specific regulators of NF-κB. A screening effort of the endogenous IKK complex allowed us to identify 5-bromo-6-methoxy-β-carboline asExpand
Discovery of a Selective Phosphoinositide-3-Kinase (PI3K)-γ Inhibitor (IPI-549) as an Immuno-Oncology Clinical Candidate.
IPI-549 demonstrates favorable pharmacokinetic properties and robust inhibition of PI3K-γ mediated neutrophil migration in vivo and is currently in Phase 1 clinical evaluation in subjects with advanced solid tumors. Expand
Recent patents for Hedgehog pathway inhibitors for the treatment of malignancy
This review covers the patent literature related to Hh pathway inhibitors for the treatment of proliferative diseases, regardless of their modes of action, and reports that most reported Hh pathways inhibitors act on the key signaling transducer Smoothened (SMO). Expand
Synthetic silvestrol analogues as potent and selective protein synthesis inhibitors.
The ability of silvestrol and analogues to selectively inhibit the translation of proteins with high requirement on the translation-initiation machinery relative to simple 5'UTR was determined by a cellular reporter assay. Expand
New developments in the discovery of small molecule Hedgehog pathway antagonists.
This review focuses on the most recent advances in the discovery of a variety of Hh pathway antagonists with particular emphasis on the medicinal chemistry approaches used to discover these Hh antagonists. Expand
Semisynthetic cyclopamine analogues as potent and orally bioavailable hedgehog pathway antagonists.
The synthesis of a novel class of hedgehog antagonists derived from cyclopamine was homologated utilizing a sequence of chemoselective cyclopropanation and stereoselectives acid-catalyzed rearrangement. Expand