Journal: Journal of Clinical Pharmacology

Article Title: An Adaptive Physiologically Based Pharmacokinetic–Driven Design to Investigate the Effect of Itraconazole and Rifampicin on the Pharmacokinetics of Molibresib (GSK525762) in Healthy Female Volunteers

doi: 10.1002/jcph.1711

Figure Lengend Snippet: Preliminary Simcyp PBPK Model Parameters

Article Snippet: Plasma samples were analyzed for molibresib and its 2 active metabolites, GSK3529246 and GSK3536835, by Covance Bioanalytical Services, LLC.

Techniques: Molecular Weight, Clinical Proteomics, Permeability

Journal: Journal of Clinical Pharmacology

Article Title: An Adaptive Physiologically Based Pharmacokinetic–Driven Design to Investigate the Effect of Itraconazole and Rifampicin on the Pharmacokinetics of Molibresib (GSK525762) in Healthy Female Volunteers

doi: 10.1002/jcph.1711

Figure Lengend Snippet: Observed and Simcyp‐simulated molibresib concentration‐time profile after a single 60‐ or 100‐mg dose (BET115521).

Article Snippet: Plasma samples were analyzed for molibresib and its 2 active metabolites, GSK3529246 and GSK3536835, by Covance Bioanalytical Services, LLC.

Techniques: Concentration Assay

Journal: Journal of Clinical Pharmacology

Article Title: An Adaptive Physiologically Based Pharmacokinetic–Driven Design to Investigate the Effect of Itraconazole and Rifampicin on the Pharmacokinetics of Molibresib (GSK525762) in Healthy Female Volunteers

doi: 10.1002/jcph.1711

Figure Lengend Snippet: Summary of Simcyp‐Simulated and Observed Molibresib PK Parameters

Article Snippet: Plasma samples were analyzed for molibresib and its 2 active metabolites, GSK3529246 and GSK3536835, by Covance Bioanalytical Services, LLC.

Techniques:

Journal: Journal of Clinical Pharmacology

Article Title: An Adaptive Physiologically Based Pharmacokinetic–Driven Design to Investigate the Effect of Itraconazole and Rifampicin on the Pharmacokinetics of Molibresib (GSK525762) in Healthy Female Volunteers

doi: 10.1002/jcph.1711

Figure Lengend Snippet: Simcyp Preliminary Prediction for Ketoconazole and Rifampicin Effects on Molibresib PK Parameters

Article Snippet: Plasma samples were analyzed for molibresib and its 2 active metabolites, GSK3529246 and GSK3536835, by Covance Bioanalytical Services, LLC.

Techniques:

Journal: Journal of Clinical Pharmacology

Article Title: An Adaptive Physiologically Based Pharmacokinetic–Driven Design to Investigate the Effect of Itraconazole and Rifampicin on the Pharmacokinetics of Molibresib (GSK525762) in Healthy Female Volunteers

doi: 10.1002/jcph.1711

Figure Lengend Snippet: Summary of PK Parameters of Molibresib, Its Two Active Metabolites (GSK3529246), and Total Active Moiety—Itraconazole Interaction (Part 1)

Article Snippet: Plasma samples were analyzed for molibresib and its 2 active metabolites, GSK3529246 and GSK3536835, by Covance Bioanalytical Services, LLC.

Techniques:

Journal: Journal of Clinical Pharmacology

Article Title: An Adaptive Physiologically Based Pharmacokinetic–Driven Design to Investigate the Effect of Itraconazole and Rifampicin on the Pharmacokinetics of Molibresib (GSK525762) in Healthy Female Volunteers

doi: 10.1002/jcph.1711

Figure Lengend Snippet: Dose‐normalized mean molibresib, active metabolite, and total active moiety concentration‐versus‐time plots when molibresib is administered alone (open symbols) or in combination (closed symbols).

Article Snippet: Plasma samples were analyzed for molibresib and its 2 active metabolites, GSK3529246 and GSK3536835, by Covance Bioanalytical Services, LLC.

Techniques: Concentration Assay

Journal: Journal of Clinical Pharmacology

Article Title: An Adaptive Physiologically Based Pharmacokinetic–Driven Design to Investigate the Effect of Itraconazole and Rifampicin on the Pharmacokinetics of Molibresib (GSK525762) in Healthy Female Volunteers

doi: 10.1002/jcph.1711

Figure Lengend Snippet: Simcyp Prediction and Actual Observed Effect of Itraconazole on PK Parameters of Molibresib, Its Two Active Metabolites (GSK3529246), and Total Active Moiety—Part 1

Article Snippet: Plasma samples were analyzed for molibresib and its 2 active metabolites, GSK3529246 and GSK3536835, by Covance Bioanalytical Services, LLC.

Techniques:

Journal: Journal of Clinical Pharmacology

Article Title: An Adaptive Physiologically Based Pharmacokinetic–Driven Design to Investigate the Effect of Itraconazole and Rifampicin on the Pharmacokinetics of Molibresib (GSK525762) in Healthy Female Volunteers

doi: 10.1002/jcph.1711

Figure Lengend Snippet: Observed and Simcyp‐simulated molibresib (A) and GSK3529246 (B) concentration‐time profiles after a single 10‐mg dose.

Article Snippet: Plasma samples were analyzed for molibresib and its 2 active metabolites, GSK3529246 and GSK3536835, by Covance Bioanalytical Services, LLC.

Techniques: Concentration Assay

Journal: Journal of Clinical Pharmacology

Article Title: An Adaptive Physiologically Based Pharmacokinetic–Driven Design to Investigate the Effect of Itraconazole and Rifampicin on the Pharmacokinetics of Molibresib (GSK525762) in Healthy Female Volunteers

doi: 10.1002/jcph.1711

Figure Lengend Snippet: Simcyp Prediction for Rifampicin Effect on PK Parameters of Molibresib and Its Two Active Metabolites (GSK3529246)

Article Snippet: Plasma samples were analyzed for molibresib and its 2 active metabolites, GSK3529246 and GSK3536835, by Covance Bioanalytical Services, LLC.

Techniques:

Journal: Journal of Clinical Pharmacology

Article Title: An Adaptive Physiologically Based Pharmacokinetic–Driven Design to Investigate the Effect of Itraconazole and Rifampicin on the Pharmacokinetics of Molibresib (GSK525762) in Healthy Female Volunteers

doi: 10.1002/jcph.1711

Figure Lengend Snippet: Summary of Observed PK Parameters of Molibresib, Its Two Active Metabolites (GSK3529246), and Total Active Moiety—Rifampicin Interaction (Part 2)

Article Snippet: Plasma samples were analyzed for molibresib and its 2 active metabolites, GSK3529246 and GSK3536835, by Covance Bioanalytical Services, LLC.

Techniques:

Journal: Journal of Clinical Pharmacology

Article Title: An Adaptive Physiologically Based Pharmacokinetic–Driven Design to Investigate the Effect of Itraconazole and Rifampicin on the Pharmacokinetics of Molibresib (GSK525762) in Healthy Female Volunteers

doi: 10.1002/jcph.1711

Figure Lengend Snippet: Preliminary Simcyp PBPK Model Parameters

Article Snippet: The Simcyp‐simulated and observed plasma concentration‐time curves for molibresib following oral administration of 60 and 100 mg are shown in Figure .

Techniques: Molecular Weight, Clinical Proteomics, Permeability

Journal: Journal of Clinical Pharmacology

Article Title: An Adaptive Physiologically Based Pharmacokinetic–Driven Design to Investigate the Effect of Itraconazole and Rifampicin on the Pharmacokinetics of Molibresib (GSK525762) in Healthy Female Volunteers

doi: 10.1002/jcph.1711

Figure Lengend Snippet: Observed and Simcyp‐simulated molibresib concentration‐time profile after a single 60‐ or 100‐mg dose (BET115521).

Article Snippet: The Simcyp‐simulated and observed plasma concentration‐time curves for molibresib following oral administration of 60 and 100 mg are shown in Figure .

Techniques: Concentration Assay

Journal: Journal of Clinical Pharmacology

Article Title: An Adaptive Physiologically Based Pharmacokinetic–Driven Design to Investigate the Effect of Itraconazole and Rifampicin on the Pharmacokinetics of Molibresib (GSK525762) in Healthy Female Volunteers

doi: 10.1002/jcph.1711

Figure Lengend Snippet: Summary of Simcyp‐Simulated and Observed Molibresib PK Parameters

Article Snippet: The Simcyp‐simulated and observed plasma concentration‐time curves for molibresib following oral administration of 60 and 100 mg are shown in Figure .

Techniques:

Journal: Journal of Clinical Pharmacology

Article Title: An Adaptive Physiologically Based Pharmacokinetic–Driven Design to Investigate the Effect of Itraconazole and Rifampicin on the Pharmacokinetics of Molibresib (GSK525762) in Healthy Female Volunteers

doi: 10.1002/jcph.1711

Figure Lengend Snippet: Simcyp Preliminary Prediction for Ketoconazole and Rifampicin Effects on Molibresib PK Parameters

Article Snippet: The Simcyp‐simulated and observed plasma concentration‐time curves for molibresib following oral administration of 60 and 100 mg are shown in Figure .

Techniques:

Journal: Journal of Clinical Pharmacology

Article Title: An Adaptive Physiologically Based Pharmacokinetic–Driven Design to Investigate the Effect of Itraconazole and Rifampicin on the Pharmacokinetics of Molibresib (GSK525762) in Healthy Female Volunteers

doi: 10.1002/jcph.1711

Figure Lengend Snippet: Summary of PK Parameters of Molibresib, Its Two Active Metabolites (GSK3529246), and Total Active Moiety—Itraconazole Interaction (Part 1)

Article Snippet: The Simcyp‐simulated and observed plasma concentration‐time curves for molibresib following oral administration of 60 and 100 mg are shown in Figure .

Techniques:

Journal: Journal of Clinical Pharmacology

Article Title: An Adaptive Physiologically Based Pharmacokinetic–Driven Design to Investigate the Effect of Itraconazole and Rifampicin on the Pharmacokinetics of Molibresib (GSK525762) in Healthy Female Volunteers

doi: 10.1002/jcph.1711

Figure Lengend Snippet: Dose‐normalized mean molibresib, active metabolite, and total active moiety concentration‐versus‐time plots when molibresib is administered alone (open symbols) or in combination (closed symbols).

Article Snippet: The Simcyp‐simulated and observed plasma concentration‐time curves for molibresib following oral administration of 60 and 100 mg are shown in Figure .

Techniques: Concentration Assay

Journal: Journal of Clinical Pharmacology

Article Title: An Adaptive Physiologically Based Pharmacokinetic–Driven Design to Investigate the Effect of Itraconazole and Rifampicin on the Pharmacokinetics of Molibresib (GSK525762) in Healthy Female Volunteers

doi: 10.1002/jcph.1711

Figure Lengend Snippet: Simcyp Prediction and Actual Observed Effect of Itraconazole on PK Parameters of Molibresib, Its Two Active Metabolites (GSK3529246), and Total Active Moiety—Part 1

Article Snippet: The Simcyp‐simulated and observed plasma concentration‐time curves for molibresib following oral administration of 60 and 100 mg are shown in Figure .

Techniques:

Journal: Journal of Clinical Pharmacology

Article Title: An Adaptive Physiologically Based Pharmacokinetic–Driven Design to Investigate the Effect of Itraconazole and Rifampicin on the Pharmacokinetics of Molibresib (GSK525762) in Healthy Female Volunteers

doi: 10.1002/jcph.1711

Figure Lengend Snippet: Observed and Simcyp‐simulated molibresib (A) and GSK3529246 (B) concentration‐time profiles after a single 10‐mg dose.

Article Snippet: The Simcyp‐simulated and observed plasma concentration‐time curves for molibresib following oral administration of 60 and 100 mg are shown in Figure .

Techniques: Concentration Assay

Journal: Journal of Clinical Pharmacology

Article Title: An Adaptive Physiologically Based Pharmacokinetic–Driven Design to Investigate the Effect of Itraconazole and Rifampicin on the Pharmacokinetics of Molibresib (GSK525762) in Healthy Female Volunteers

doi: 10.1002/jcph.1711

Figure Lengend Snippet: Simcyp Prediction for Rifampicin Effect on PK Parameters of Molibresib and Its Two Active Metabolites (GSK3529246)

Article Snippet: The Simcyp‐simulated and observed plasma concentration‐time curves for molibresib following oral administration of 60 and 100 mg are shown in Figure .

Techniques:

Journal: Journal of Clinical Pharmacology

Article Title: An Adaptive Physiologically Based Pharmacokinetic–Driven Design to Investigate the Effect of Itraconazole and Rifampicin on the Pharmacokinetics of Molibresib (GSK525762) in Healthy Female Volunteers

doi: 10.1002/jcph.1711

Figure Lengend Snippet: Summary of Observed PK Parameters of Molibresib, Its Two Active Metabolites (GSK3529246), and Total Active Moiety—Rifampicin Interaction (Part 2)

Article Snippet: The Simcyp‐simulated and observed plasma concentration‐time curves for molibresib following oral administration of 60 and 100 mg are shown in Figure .

Techniques:

Journal: Pharmaceutics

Article Title: Advancements in Virtual Bioequivalence: A Systematic Review of Computational Methods and Regulatory Perspectives in the Pharmaceutical Industry

doi: 10.3390/pharmaceutics16111414

Figure Lengend Snippet: A summary of the studies included in the scoping review, outlining the pharmaceutical drugs involved, therapeutic indications, in silico tools used, and the key findings related to bioequivalence.

Article Snippet: Riddell, K. et al. [ ], 2020 , PubMed , Molibresib , Anticancer , SimCYP ® version 14.

Techniques: In Silico

Journal: Genes & Diseases

Article Title: Differences between lung adenocarcinoma and lung squamous cell carcinoma: Driver genes, therapeutic targets, and clinical efficacy

doi: 10.1016/j.gendis.2024.101374

Figure Lengend Snippet: Epigenetic targeted therapies for lung adenocarcinoma and lung squamous cell carcinoma.

Article Snippet: , Molibresib , Solid tumor , Phase I/II , EUCTR2014-004982-25-ES , Molibresib , 225 , Not yet recruiting , GlaxoSmithKline, S.A..

Techniques:

Journal: Clinical Epigenetics

Article Title: Drugging the epigenome in the age of precision medicine

doi: 10.1186/s13148-022-01419-z

Figure Lengend Snippet: Summary of epigenetic approaches and molecules

Article Snippet: Bromodomain inhibitors , Molibresib , Small molecule , GlaxoSmithKline , Clinical development discontinued.

Techniques: Histone Deacetylase Assay, Inhibition

Journal: Cells

Article Title: Inhibition of BRD4 Promotes Pexophagy by Increasing ROS and ATM Activation

doi: 10.3390/cells11182839

Figure Lengend Snippet: Inhibition of BRD4 promotes pexophagy in RPE cells. ( A ) RPE/mRFP-EGFP-SKL cells were treated with inhibitors of BRD4 [molibresib (10 µM), I-BET151 (10 µM), dBET1 (10 µM)] for 72 h. The cells were fixed for imaging under a fluorescence microscope. The numbers of cell with EGFP(+)- and mRFP(+)-labeled autophagosomes or EGFP(-) and mRFP(+)-labeled autolysosomes, which displayed the peroxisomal reporter mRFP-EGFP-SKL due to lysosomal delivery, were counted and are presented as percentages; ( B ) HeLa cells stably expressing pmTurquiose2-Peroxi, pmTurquiose2-Mito, pmTurquiose2-ER, or pmTurquiose2-Golgi were treated with molibresib (10 µM) for 72 h and stained with DRAQ (red). Cellular organelles were imaged by confocal microscopy. The scale bar indicates 20 µm; ( C , D ) RPE/mRFP-EGFP-SKL cells were transiently transfected with siRNA targeting BRD4 (siBRD4), and then, EGFP and mRFP fluorescence was imaged and quantified ( C ); reduced expression of BRD4 by siRNA was verified by Western blotting ( D ). (Data indicate means ± S.E.M. *** p < 0.001).

Article Snippet: Molibresib (10676), I-BET151 (11181) and dBET1 (18044) were obtained from Cayman Chemical Co. (Ann Arbor, MI, USA).

Techniques: Inhibition, Imaging, Fluorescence, Microscopy, Labeling, Stable Transfection, Expressing, Staining, Confocal Microscopy, Transfection, Western Blot

Journal: Cells

Article Title: Inhibition of BRD4 Promotes Pexophagy by Increasing ROS and ATM Activation

doi: 10.3390/cells11182839

Figure Lengend Snippet: Loss of ATG7 blocks molibresib-induced pexophagy in HeLa cells. ( A , B ) HeLa cells pre-treated with molibresib (10 µM) for 48 h were further incubated with or without bafilomycin A1 (Baf. A1, 25 nM) for 6 h. Then, the cells were harvested to analyze by Western blotting with indicated antibodies ( A ); the cells were stained with anti-ABCD antibody (red) and Hoechst 33,342 (blue). The number of peroxisomes per cell was calculated by assessing > 100 cells ( B ); ( C ) wild-type and ATG7-knockout HeLa cells were treated with molibresib (10 µM) for 48 h. The cells were stained with anti-ABCD3 antibody (red) and Hoechst 33,342 dye (blue). The number of peroxisomes per cell was calculated by assessing approximately 100 cells; ( D ) wild-type and ATG7-knockout HeLa cells were treated with molibresib (10 µM) for 48 h, and then harvested for analysis by Western blotting with the indicated antibodies; ( E ) HeLa cells were transiently transfected with scrambled siRNA (Sc) or validated siRNA targeting for NBR1 (siNBR1) or p62 (sip62). After 24 h, the cells were further treated with molibresib (10 µM) for 48 h and stained with anti-ABCD3 antibody (red) and Hoechst 33,342 dye (blue). The number of peroxisomes per cell was calculated by assessing approximately 100 cells; the scale bar indicates 20 µm. (Data indicate means ± S.E.M. * p < 0.05, *** p < 0.001, ns: not significant).

Article Snippet: Molibresib (10676), I-BET151 (11181) and dBET1 (18044) were obtained from Cayman Chemical Co. (Ann Arbor, MI, USA).

Techniques: Incubation, Western Blot, Staining, Knock-Out, Transfection

Journal: Cells

Article Title: Inhibition of BRD4 Promotes Pexophagy by Increasing ROS and ATM Activation

doi: 10.3390/cells11182839

Figure Lengend Snippet: Inhibition of BRD4 promotes pexophagy by increasing the ROS levels in HeLa cells. ( A ) HeLa cells were treated with molibresib (10 µM) with or without NAC (1 mM) for 48 h. Then, the cells were incubated with fluorescent DCFH-DA dye (10 µM, 10 min). The cells were imaged (scale bar 50 µm), and DCFH-DA fluorescence intensity was measured using image processing software ImageJ; ( B ) HeLa/pexo-HyPer cells were treated with molibresib (10 µM) with or without NAC (1 mM) for 48 h. The level of peroxisomal H 2 O 2 was imaged (scale bar, 50 μm) and measured using the fluorescence intensity of HyPer-PTS1; ( C ) HeLa cells were treated with molibresib (10 µM) with or without NAC (1 mM) for 48 h. Then, the cells were immunostained with anti-ABCD3 antibody (red) and Hoechst 33,342 dye (blue) to count the number of peroxisomes in cells. Representative cell images are presented (C, scale bar 20 µm). The experiments were repeated at least three times. (Data indicate means ± S.E.M. ** p < 0.01, *** p < 0.001, ns: not significant).

Article Snippet: Molibresib (10676), I-BET151 (11181) and dBET1 (18044) were obtained from Cayman Chemical Co. (Ann Arbor, MI, USA).

Techniques: Inhibition, Incubation, Fluorescence, Software

Journal: Cells

Article Title: Inhibition of BRD4 Promotes Pexophagy by Increasing ROS and ATM Activation

doi: 10.3390/cells11182839

Figure Lengend Snippet: Inhibition of BRD4 activates ATM to promote pexophagy in HeLa cells. ( A ) HeLa cells were treated with molibresib (10 µM) with or without NAC (1 mM) for 48 h. The cells were harvested and analyzed by Western blotting with the indicated antibodies; ( B ) HeLa cells were treated with molibresib (10 µM) with or without KU55933 (10 µM) for 48 h. Then, the cells were immunostained with anti-ABCD3 antibody (red) and Hoechst 33,342 dye (blue) to count the peroxisomes. Representative cell images are presented (scale bar 20 µm). The experiments were repeated at least three times. (Data indicate means ± S.E.M. *** p < 0.001, ns: not significant).

Article Snippet: Molibresib (10676), I-BET151 (11181) and dBET1 (18044) were obtained from Cayman Chemical Co. (Ann Arbor, MI, USA).

Techniques: Inhibition, Western Blot