Hot Natural Products & Bioactive Compounds

Potent and selective inhibitor of PI 3-kinase <span class='symbol'>&#946;</span> (PI 3-K<span class='symbol'>&#946;</span>) (IC₅₀ values are 0.69, 13.6, 47.8 and 136 nM for PI 3-K<span class='symbol'>&#946;</span>, PI 3-K<span class='symbol'>&#948;</span>, PI 3-K<span class='symbol'>&#947;</span> and PI 3-K<span class='symbol'>&#945;</span>, respectively). Selectively inhibits <em>in vivo</em> growth of the PTEN-deficient tumor xenografts HCC70 and PC3. Also exhibits antithrombotic activity.

Thiazovivin is a novel ROCK inhibitor with IC50 of 0.5 μM in a cell-free assay, promotes hESC survival after single-cell dissociation.Although displaying little impact on cell proliferation, Thiazovivin treatment significantly enhances the survival of human embryonic stem cells (hESCs) after enzymatic dissociation more than 30-fold, while homogenously maintaining pluripotency with the characteristic colony morphology, expression of typical pluripotency markers such as alkaline phosphatase (ALP), and normal karyotype. Dissociated hESCs treated with Thiazovivin display dramatically increased adhesion to matrigel- or laminin-coated plates but not to gelatin-coated plates within a few hours. Thiazovivin treatment increases cell-ECM adhesion-mediated β1 integrin activity, which synergizes with growth factors to promote cell survival. In addition to activating integrin, Thiazovivin but not Tyrintegin (Ptn) protects hESCs from death in the absence of ECM in suspension through E-cadherin-mediated cell-cell interaction. Thiazovivin treatment potently inhibits endocytosis of E-cadherin, consequently stabilizing E-cadherin on the cell surface and leading to reestablishment of cell-cell interaction, which is essential for hESC survival in ECM-free conditions. Thiazovivin but not Tyrintegin (Ptn) at 2 μM inhibits Rho-associated kinase (ROCK) activity and protects hESCs at a similar level as the widely used selective ROCK inhibitor Y-27632 at 10 μM, suggesting that Rho-ROCK signaling regulates cell-ECM and cell-cell adhesion. Thiazovivin at 1 μM increases the reprogramming efficiency of CB mononuclear cells to induced pluripotent stem cells (iPSCs) by more than 10 times.

Inhibitor of mitochondrial ATP synthase and uncoupler of oxidative phosphorylation. Antibiotic; exhibits anti-tumor activity.

Selective inhibitor of transforming growth factor-<span class='symbol'>&beta;</span> receptor I (ALK5, TGF-<span class='symbol'>&beta;</span>RI) (IC₅₀ = 14.3 nM). Inhibits TGF-<span class='symbol'>&beta;</span>1-induced smad2/3 nuclear localization and TGF-<span class='symbol'>&beta;</span>RI-induced mRNA expression in kidney cells. Attenuates bleomycin-induced pulmonary fibrosis.

Selective Rho-kinase inhibitor (IC50 values are 14, 780 and 1940 nM for ROCK1, RSK and p70S6K respectively). Reverses adrenalin-induced contraction of the rat aortic ring (IC50 = 190 nM) and causes a dose-dependent decrease in mean arterial blood pressure in spontaneous hypertensive rats. Orally active.

High affinity and selective p38 kinase inhibitor (K_d = 50-100 pM). Exhibits no significant inhibition on a panel of related kinases. Inhibits LPS-induced TNF<span class='symbol'>&#945;</span> production in human PBMCs and whole blood (IC₅₀ values are 21 and 960 nM, respectively). Also inhibits JNK2<span class='symbol'>&#945;</span>2 and c-Raf-1 (IC₅₀ values are 98 nM and 1.4 <span class='symbol'>&#956;</span>M, respectively). Cell permeable.

Receptor-selective acetylenic retinoid; binds at retinoid acid receptors (RAR) -<span class='symbol'>&#946;</span> and -<span class='symbol'>&#947;</span>. Topically used for the treatment of skin disorders, particularly psoriasis and acne. Implicated in the treatment of basal cell carcinomas; induces upregulation of Bax <em>in vivo</em>. Exhibits antiproliferative and proapoptotic activity. Upregulates TIGs (Tazarotene-induced genes), including the cell adhesion molecule TIG1 and the tumor-suppressor TIG3.

Cyclic nucleotide-dependent protein kinase inhibitor and Rho-associated kinase inhibitor (IC₅₀ = 10.7 <span class='symbol'>&mu;</span>M). Suppress MMP-2 expression and induce apoptosis in glioblastoma cells <em>in vivo</em>. Ca²⁺ antagonist and vasodilator. Also inhibits proliferation of vascular smooth muscle cells.