A5043310564- Pancreatic and Hepatic Oncology Research
- Genomics and Rare Diseases
- Cancer Genomics and Diagnostics
- Genetic factors in colorectal cancer
- Advanced Breast Cancer Therapies
- TGF-β signaling in diseases
- CRISPR and Genetic Engineering
- PARP inhibition in cancer therapy
- Colorectal Cancer Treatments and Studies
- Cancer Research and Treatments
- Diabetes Treatment and Management
- Chromatin Remodeling and Cancer
- Renal cell carcinoma treatment
- Heat shock proteins research
- Genomics and Chromatin Dynamics
- Colorectal Cancer Surgical Treatments
- Epigenetics and DNA Methylation
- Health and Medical Research Impacts
- Biomedical Ethics and Regulation
- Cancer-related gene regulation
- Computational Drug Discovery Methods
- Enzyme Structure and Function
- Radiomics and Machine Learning in Medical Imaging
Sanofi (France)
2011-2023
A novel class of heat shock protein 90 (Hsp90) inhibitors was developed after a low throughput screen (LTS) focused library containing approximately 21K compounds selected by virtual screening. The initial [1-{3-H-imidazo[4–5-c]pyridin-2-yl}-3,4-dihydro-2H-pyrido[2,1-a]isoindole-6-one] (1) compound showed moderate activity (IC50 = 7.6 μM on Hsp82, the yeast homologue Hsp90). high-resolution X-ray structure shows that 1 binds into an "induced" hydrophobic pocket, 10–15 Å away from...
The TGFβ signaling mediator SMAD4 is frequently mutated or deleted in colorectal and pancreatic cancers. acts as a tumor suppressor its loss associated with poorer patient outcomes. purpose of this study was to find synthetic lethal interactions deficiency novel therapeutic strategies for the treatment patients SMAD4-deficient Using pooled lentiviral single-guide RNA libraries, we conducted genome-wide loss-of-function screens Cas9-expressing cancer cells harboring altered wild-type SMAD4....
<p>Gene_scoreMageckComparison</p>
<p>Map of the plasmids to express inducible SMAD4 and Cas9</p>
<p>Behavior of sgRNAs targeting essential and nonessential genes in the screen samples.</p>
<p>QCsummary</p>
<p>Short validation screen in plate to validate the top 4 synthetic lethal gene candidates</p>
<p>94 Putative synthetic lethal genes identified in the screen</p>
<p>Determination of RAB10 localization</p>
<p>sgRNAs against RAB10</p>
<p>Validation of RAB10 susceptibility in two additional cell lines.</p>
<p>sgRNAcounts</p>
<p>library preparation primers</p>
<p>S2. Quality check of the CRISPR screen samples.</p>
<p>Proteins level assessment by western blotting</p>
<p>RAB10 essentiality in cells having altered SMAD4 is confirmed by the vitro CRISPR screen database DepMap</p>
<p>sgRNAscoreMageckComparison</p>
<div>Abstract<p>The TGF-β signaling mediator SMAD4 is frequently mutated or deleted in colorectal and pancreatic cancers. acts as a tumor suppressor its loss associated with poorer patient outcomes. The purpose of this study was to find synthetic lethal interactions deficiency order novel therapeutic strategies for the treatment patients SMAD4-deficient Using pooled lentiviral sgRNA libraries, we conducted genome-wide loss-of-function screens Cas9-expressing cancer cells...
<div><p>The TGFβ signaling mediator SMAD4 is frequently mutated or deleted in colorectal and pancreatic cancers. acts as a tumor suppressor its loss associated with poorer patient outcomes. The purpose of this study was to find synthetic lethal interactions deficiency novel therapeutic strategies for the treatment patients SMAD4-deficient Using pooled lentiviral single-guide RNA libraries, we conducted genome-wide loss-of-function screens Cas9-expressing cancer cells harboring...
<p>RAB10 essentiality in cells having altered SMAD4 is confirmed by the vitro CRISPR screen database DepMap</p>
<p>Short validation screen in plate to validate the top 4 synthetic lethal gene candidates</p>
<p>94 Putative synthetic lethal genes identified in the screen</p>
<p>Gene_scoreMageckComparison</p>
<p>Proteins level assessment by western blotting</p>
<p>Determination of RAB10 localization</p>