Richard J. Bellin
A5004428348- Protein Degradation and Inhibitors
- Multiple Myeloma Research and Treatments
- Acute Myeloid Leukemia Research
- HIV/AIDS drug development and treatment
- Peptidase Inhibition and Analysis
- Histone Deacetylase Inhibitors Research
- Cancer-related gene regulation
- Cancer-related Molecular Pathways
- Chronic Lymphocytic Leukemia Research
- RNA Interference and Gene Delivery
- Ubiquitin and proteasome pathways
- Cancer, Lipids, and Metabolism
- Chronic Myeloid Leukemia Treatments
- Advanced Breast Cancer Therapies
- Myeloproliferative Neoplasms: Diagnosis and Treatment
AbbVie (United States)
2017-2023
The University of Texas MD Anderson Cancer Center
2023
Statins have shown promise as anticancer agents in experimental and epidemiologic research. However, any benefit that they provide is likely context-dependent, for example, applicable only to certain cancers or combination with specific drugs. We report inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) using statins enhances the proapoptotic activity B cell lymphoma-2 (BCL2) inhibitor venetoclax (ABT-199) primary leukemia lymphoma cells but not normal human peripheral...
Abstract Ten percent to 15% of all lung cancers are small-cell cancer (SCLC). SCLC usually grows and metastasizes before it is diagnosed relapses rapidly upon treatment. Unfortunately, no new targeted agent has been approved in the past 30 years for patients with SCLC. The BET (bromodomain extraterminal) proteins bind acetylated histones recruit protein complexes promote transcription initiation elongation. have shown regulate expression key genes oncogenesis, such as MYC, CCND2, BCL2L1....
Abstract Dual bromodomain BET inhibitors that bind with similar affinities to the first and second bromodomains across BRD2, BRD3, BRD4, BRDT have displayed modest activity as monotherapy in clinical trials. Thrombocytopenia, closely followed by symptoms characteristic of gastrointestinal toxicity, presented dose-limiting adverse events may prevented escalation higher dose levels required for more robust efficacy. ABBV-744 is a highly selective inhibitor four family proteins. In contrast...
Abstract Many small-molecule inhibitors that target both bromodomains of the BET family proteins (pan inhibitors) are undergoing studies in clinical trials. Emerging data beginning to suggest responses these pan subsets hematologic malignancies may be modest and short lived, perhaps due, at least part, tolerability issues limit dosing levels. We hypothesized selective inhibition four eight might retain anticancer activities certain tumor while alleviating some liabilities inhibitors, thus...
<div>Abstract<p>Dual bromodomain BET inhibitors that bind with similar affinities to the first and second bromodomains across BRD2, BRD3, BRD4, BRDT have displayed modest activity as monotherapy in clinical trials. Thrombocytopenia, closely followed by symptoms characteristic of gastrointestinal toxicity, presented dose-limiting adverse events may prevented escalation higher dose levels required for more robust efficacy. ABBV-744 is a highly selective inhibitor four family...
<div>Abstract<p>Dual bromodomain BET inhibitors that bind with similar affinities to the first and second bromodomains across BRD2, BRD3, BRD4, BRDT have displayed modest activity as monotherapy in clinical trials. Thrombocytopenia, closely followed by symptoms characteristic of gastrointestinal toxicity, presented dose-limiting adverse events may prevented escalation higher dose levels required for more robust efficacy. ABBV-744 is a highly selective inhibitor four family...
<p>Supplementary figure and table legends</p>
<p>Figure S2. ABBV-744 retains strong transcription regulatory activities in AML cells and it did not alter the baseline expression of representative IFN-r or PMA responsive genes.</p>
<p>Primary patient sample information</p>
<p>Figure S1.ABBV-744 exhibits potent anti-proliferative activity against AML cells through cell cycle arrest and induction of apoptosis.</p>
<p>Tumor growth inhibition in cell line-based xenograft models and supporting statistics.</p>
<p>Figure S3.Comparison of ABBV-744 and GSK046 BD2 selective compounds.</p>
<p>Figure S3.Comparison of ABBV-744 and GSK046 BD2 selective compounds.</p>
<p>Figure S4.ABBV-744 displaces BRD4 from regulatory regions of BCL2, BCL2L1 and RUNX1 in sensitive AML cells but not insensitive line.</p>
<p>Supplementary figure and table legends</p>
<p>Tumor growth inhibition in cell line-based xenograft models and supporting statistics.</p>
<p>Figure S6.Identification of biomarker response to ABBV-744/venetoclax therapy.</p>
<p>Figure S2. ABBV-744 retains strong transcription regulatory activities in AML cells and it did not alter the baseline expression of representative IFN-r or PMA responsive genes.</p>
<p>Figure S5.Antitumor activity of ABBV-744/venetoclax in AML xenograft model and primary samples</p>
<p>Figure S4.ABBV-744 displaces BRD4 from regulatory regions of BCL2, BCL2L1 and RUNX1 in sensitive AML cells but not insensitive line.</p>
<p>Figure S6.Identification of biomarker response to ABBV-744/venetoclax therapy.</p>
<p>Figure S5.Antitumor activity of ABBV-744/venetoclax in AML xenograft model and primary samples</p>
<p>Figure S1.ABBV-744 exhibits potent anti-proliferative activity against AML cells through cell cycle arrest and induction of apoptosis.</p>