Journal: Frontiers in Endocrinology

Article Title: Chemistry and Hypoglycemic Activity of GPR119 Agonist ZB-16

doi: 10.3389/fendo.2018.00543

Figure Lengend Snippet: Binding of compounds from the ZB series to hERG.

Article Snippet: Ref. inh. IC 50 Ref. inh. IC 50 (Invitrogen) , 3.5 * 10 −7 2.1 * 10 −7 , 6.9 * 10 −8 7 * 10 −8 , 1.6 * 10 −8 3 * 10 −8 , 2.9 * 10 −8 4 * 10 −8 , 3.0 * 10 −9 10 * 10 −9.

Techniques: Binding Assay, Concentration Assay

Journal: Frontiers in Endocrinology

Article Title: Chemistry and Hypoglycemic Activity of GPR119 Agonist ZB-16

doi: 10.3389/fendo.2018.00543

Figure Lengend Snippet: Inhibition of CYP450 isoforms by ZB-16 and ZB-20 test compounds and standard compounds.

Article Snippet: Ref. inh. IC 50 Ref. inh. IC 50 (Invitrogen) , 3.5 * 10 −7 2.1 * 10 −7 , 6.9 * 10 −8 7 * 10 −8 , 1.6 * 10 −8 3 * 10 −8 , 2.9 * 10 −8 4 * 10 −8 , 3.0 * 10 −9 10 * 10 −9.

Techniques: Inhibition

Journal: Journal of Medicinal Chemistry

Article Title: UNC2025 , a Potent and Orally Bioavailable MER/FLT3 Dual Inhibitor

doi: 10.1021/jm500749d

Figure Lengend Snippet: 11 Inhibits activation of Mer in acute leukemia cells. 697 Cells were treated with the indicated concentrations of 11 for 1 h. Pervanadate was added to cultures for 3 min to stabilize the phosphorylated form of Mer. Mer was immunoprecipitated from cell lysates, and total MER protein and Mer phosphoprotein (p-Mer) were detected by immunoblot. (A) Representative Western blots. (B) Relative levels of p-Mer and Mer proteins were determined by densitometry. Mean values ± standard error derived from 3 independent experiments are shown. IC 50 = 2.7 nM with a 95% confidence interval from 1.8 to 4.2 nM.

Article Snippet: In fact, a plot of in vitro potency versus cellular phospho-protein potency that utilizes the Mer K i and the Carna IC 50 ’s for Flt3, Axl, and Tyro3 (Figure ) results in a correlation coefficient ( R 2 ) of 0.98 with a predicted 50-fold shift in potency in the cellular assay environment relative to Carna IC 50 ’s.

Techniques: Activation Assay, Immunoprecipitation, Western Blot, Derivative Assay

Journal: Journal of Medicinal Chemistry

Article Title: UNC2025 , a Potent and Orally Bioavailable MER/FLT3 Dual Inhibitor

doi: 10.1021/jm500749d

Figure Lengend Snippet: 11 Inhibits colony formation in Mer-dependent and Flt3-dependent tumor cell lines. (A) A549 NSCLC cells or (B) Molm-14 AML cells were cultured in 0.35% soft agar overlaid with medium containing 11 , a negative control ( 20 ) (300 nM for A549 NSCLC cells and 50 nM for Molm-14 AML cells), or vehicle. Medium and compounds were refreshed 3 times per week. Colonies were stained and counted. Mean values ± standard error derived from 3 to 4 independent experiments are shown. Statistically significant differences were determined using the student’s paired t test (* p < 0.05, ** p ≤ 0.005, *** P < 0.0005 relative to vehicle only). (C) Structure and enzymatic IC 50 ’s of compound 20 .

Article Snippet: In fact, a plot of in vitro potency versus cellular phospho-protein potency that utilizes the Mer K i and the Carna IC 50 ’s for Flt3, Axl, and Tyro3 (Figure ) results in a correlation coefficient ( R 2 ) of 0.98 with a predicted 50-fold shift in potency in the cellular assay environment relative to Carna IC 50 ’s.

Techniques: Cell Culture, Negative Control, Staining, Derivative Assay

Journal: Journal of Medicinal Chemistry

Article Title: UNC2025 , a Potent and Orally Bioavailable MER/FLT3 Dual Inhibitor

doi: 10.1021/jm500749d

Figure Lengend Snippet: 11 Selectively inhibits Mer in cell-based assays. 32D Cells stably expressing chimeric receptors consisting of the extracellular ligand-binding and transmembrane domains of the EGF receptor and the intracellular kinase domain of Mer, Axl, or Tyro3 were treated with 11 or vehicle for 1 h prior to stimulation for 15 min with 100 ng/mL EGF. Chimeric proteins were immunoprecipitated from whole cell lysates and phospho-tyrosine-containing and total proteins were detected by Western blot. (A) Representative Western blots are shown. (B and C) Phosphorylated and total protein levels were determined by densitometry. Mean values ± standard error derived from 3 independent experiments are shown. IC 50 values and 95% confidence intervals were determined by nonlinear regression and are 2.7 nM (1.7–4.2 nM) for Mer, 122 nM (64–230 nM) for Axl, and 301 nM (110–820 nM) for Tyro3.

Article Snippet: In fact, a plot of in vitro potency versus cellular phospho-protein potency that utilizes the Mer K i and the Carna IC 50 ’s for Flt3, Axl, and Tyro3 (Figure ) results in a correlation coefficient ( R 2 ) of 0.98 with a predicted 50-fold shift in potency in the cellular assay environment relative to Carna IC 50 ’s.

Techniques: Stable Transfection, Expressing, Ligand Binding Assay, Immunoprecipitation, Western Blot, Derivative Assay

Journal: Journal of Medicinal Chemistry

Article Title: UNC2025 , a Potent and Orally Bioavailable MER/FLT3 Dual Inhibitor

doi: 10.1021/jm500749d

Figure Lengend Snippet: Correlation of in vitro and phospho-protein potency for 11 versus Mer, Flt3, Axl, and Tyro3 utilizing the Morrison K i for Mer and the IC 50 ’s from Table for all others.

Article Snippet: In fact, a plot of in vitro potency versus cellular phospho-protein potency that utilizes the Mer K i and the Carna IC 50 ’s for Flt3, Axl, and Tyro3 (Figure ) results in a correlation coefficient ( R 2 ) of 0.98 with a predicted 50-fold shift in potency in the cellular assay environment relative to Carna IC 50 ’s.

Techniques: In Vitro

Journal: Journal of Medicinal Chemistry

Article Title: UNC2025 , a Potent and Orally Bioavailable MER/FLT3 Dual Inhibitor

doi: 10.1021/jm500749d

Figure Lengend Snippet: Carna IC 50 of the Top 10 kinases and Met kinase Inhibited by 11

Article Snippet: In fact, a plot of in vitro potency versus cellular phospho-protein potency that utilizes the Mer K i and the Carna IC 50 ’s for Flt3, Axl, and Tyro3 (Figure ) results in a correlation coefficient ( R 2 ) of 0.98 with a predicted 50-fold shift in potency in the cellular assay environment relative to Carna IC 50 ’s.

Techniques: Sequencing

Journal: Evidence-based Complementary and Alternative Medicine : eCAM

Article Title: Antibacterial and Cytotoxic Activity of Compounds Isolated from Flourensia oolepis

doi: 10.1155/2015/912484

Figure Lengend Snippet: Anticancer effects of compounds 1 – 5 isolated from Flourensia oolepis extract toward sensitive and resistant leukemic cells.

Article Snippet: When the medium growth inhibitory concentration of 1 toward HEK293T (IC 50 = 67.0 μ M) and PBMC (IC 50 = 82.8 μ M) was compared to that of CCRF-CEM (IC 50 = 6.6 μ M), SIs of 10.1 and 12.5 were, respectively, observed, while in the case of CEM/ADR5000 (IC 50 9.9 μ M), the IC 50 ratios were 6.8 and 8.4, respectively.

Techniques: Isolation

Journal: Evidence-based Complementary and Alternative Medicine : eCAM

Article Title: Antibacterial and Cytotoxic Activity of Compounds Isolated from Flourensia oolepis

doi: 10.1155/2015/912484

Figure Lengend Snippet: CCRF-CEM and K562 cells treated with 1% ethanol (controls (a) and (c), resp.) or with 1 at 2 × IC 50 ((b) and (d), resp.) for 72 h were stained with PI for cell cycle phase distribution analysis by flow cytometry. The percentages of cells in each phase, including sub-G1 (hypodiploid), are indicated.

Article Snippet: When the medium growth inhibitory concentration of 1 toward HEK293T (IC 50 = 67.0 μ M) and PBMC (IC 50 = 82.8 μ M) was compared to that of CCRF-CEM (IC 50 = 6.6 μ M), SIs of 10.1 and 12.5 were, respectively, observed, while in the case of CEM/ADR5000 (IC 50 9.9 μ M), the IC 50 ratios were 6.8 and 8.4, respectively.

Techniques: Staining, Flow Cytometry

Journal: Evidence-based Complementary and Alternative Medicine : eCAM

Article Title: Antibacterial and Cytotoxic Activity of Compounds Isolated from Flourensia oolepis

doi: 10.1155/2015/912484

Figure Lengend Snippet: Effects of compound 1 on cell death process. CCRF-CEM and K562 cells were incubated for 72 h with 1% ethanol (controls (a) and (c), resp.) or with 2 × IC 50 of 1 ((b) and (d), resp.). Apoptotic effect of 1 was evaluated by flow cytometry analysis after double staining with Annexin V-APC and PI. Annexin V-APC intensity is represented on the x -axis and PI fluorescence intensity is represented on the y -axis.

Article Snippet: When the medium growth inhibitory concentration of 1 toward HEK293T (IC 50 = 67.0 μ M) and PBMC (IC 50 = 82.8 μ M) was compared to that of CCRF-CEM (IC 50 = 6.6 μ M), SIs of 10.1 and 12.5 were, respectively, observed, while in the case of CEM/ADR5000 (IC 50 9.9 μ M), the IC 50 ratios were 6.8 and 8.4, respectively.

Techniques: Incubation, Flow Cytometry, Double Staining, Fluorescence