Devansh Singh
A5066342013- Nitric Oxide and Endothelin Effects
- Cancer, Hypoxia, and Metabolism
- Mechanisms of cancer metastasis
- Metabolism, Diabetes, and Cancer
- Amino Acid Enzymes and Metabolism
- Enzyme Structure and Function
- Colorectal Cancer Treatments and Studies
- Renal cell carcinoma treatment
- Receptor Mechanisms and Signaling
- Ubiquitin and proteasome pathways
- Engineering Applied Research
- Protein Kinase Regulation and GTPase Signaling
- Hand Gesture Recognition Systems
- Pancreatic and Hepatic Oncology Research
- Enzyme function and inhibition
- 14-3-3 protein interactions
Graphic Era University
2024
BridgeBio (United States)
2024
Institute of Management Technology
2024
Calithera (United States)
2021
Abstract The glycine to cysteine mutation on codon 12 of KRAS (KRASG12C) is found in ~15% non-small cell lung cancers and a low percentage colorectal pancreatic adenocarcinomas. This activating pushes the balance cellular towards its active, GTP-bound (ON) state that signals downstream drives proliferation. Recently approved inhibitors KRASG12C bind sequester oncogenic protein inactive GDP-bound (OFF) state, have demonstrated clinical efficacy; however, median duration response has been...
<div>Abstract<p>Approved inhibitors of KRAS<sup>G12C</sup> prevent oncogenic activation by sequestering the inactive, GDP-bound (OFF) form rather than directly binding and inhibiting active, GTP-bound (ON) form. This approach provides no direct target coverage active protein. Expectedly, adaptive resistance to (OFF)-only is observed in association with increased expression activity KRAS<sup>G12C</sup>(ON). To provide optimal coverage, we have developed...
<p>Supplementary Figure S2 shows the electron density map for BBO-8520 bound to KRAS G12C in GDP and GppNHp states</p>
<p>Supplementary Figure S6 shows that BBO-8520 anti-tumor activity in NCI-H358 CDX sotorasib-resistant tumors</p>
<p>Supplementary Figure S1 shows the Kinact/KI values for BBO-8520, sotorasib and adagrasib in biochemical cell-based assays</p>
<p>Supplementary Material and Methods</p>
<p>Supplementary Figure S5 shows that BBO-8520 demonstrates in vivo pERK inhibition, KRAS G12C target engagement and is well tolerated</p>
<p>Supplementary Figure S3 shows the activity of BBO-8520, sotorasib, and adagrasib on Ba/F3 cells with KRAS G12C mutations altered states GTP hydrolysis</p>
<p>Supplementary Figure S4 summarizes cysteine profiling, RNA-seq and kinomescan studies demonstrating that BBO-8520 is selective for KRAS G12C MAPK inhibition.</p>
Dysregulated metabolism is a hallmark of cancer that manifests through alterations in bioenergetic and biosynthetic pathways to enable tumor cell proliferation survival. Tumor cells exhibit high rates glycolysis, phenomenon known as the Warburg effect, an increase glutamine consumption support tricarboxylic acid (TCA) cycle. Renal carcinoma (RCC) tumors express levels glutaminase (GLS), enzyme required for first step metabolic conversion glutamate entry into TCA We found RCC are highly...
Approved inhibitors of KRASG12C prevent oncogenic activation by sequestering the inactive, GDP-bound (OFF) form rather than directly binding and inhibiting active, GTP-bound (ON) form. This approach provides no direct target coverage active protein. Expectedly, adaptive resistance to (OFF)-only is observed in association with increased expression activity KRASG12C(ON). To provide optimal coverage, we have developed BBO-8520, a first-in-class, dual inhibitor KRASG12C(ON) forms. BBO-8520 binds...
Polyp is an earlier stage of cancer development in gastro-intestinal tract. Despite the fact that numerous techniques for automatic segmentation and detection polyps have been developed, it still remains open problem. Examining color images captured by board camera endoscopy contemplated most reliable method detectingdeveloping polyps. To automate this process, paper we present a modified U-Net Neural Network based algorithm. This algorithm binary classifier which labels pixels as part polyp...
Abstract Background: Mutations on codon 12 of KRAS are observed in many human cancers. KRASG12C mutations found ~15% non-small cell lung cancers and a low percentage colorectal pancreatic adenocarcinomas. These activating push cellular balance towards its active, GTP-bound state that signals downstream drives transformation. Recently approved inhibitors bind sequester the oncogenic protein inactive, GDP-bound state, have demonstrated clinical efficacy patients with cancers, including NSCLC,...