A5052430339- Biofuel production and bioconversion
- Computational Drug Discovery Methods
- Microbial Metabolic Engineering and Bioproduction
- Click Chemistry and Applications
- Cell Image Analysis Techniques
- Porphyrin and Phthalocyanine Chemistry
- Ubiquitin and proteasome pathways
- Chemical Synthesis and Analysis
- Mass Spectrometry Techniques and Applications
- Hemoglobin structure and function
- Enzyme Production and Characterization
- Peptidase Inhibition and Analysis
- Monoclonal and Polyclonal Antibodies Research
- Protein Degradation and Inhibitors
- Protein Structure and Dynamics
- Molecular Sensors and Ion Detection
- Innovative Microfluidic and Catalytic Techniques Innovation
- Microbial Natural Products and Biosynthesis
- Cancer, Hypoxia, and Metabolism
- Antimicrobial Peptides and Activities
- Hedgehog Signaling Pathway Studies
- Enzyme Catalysis and Immobilization
- Gene Regulatory Network Analysis
- Immune Response and Inflammation
- Photosynthetic Processes and Mechanisms
Novartis (United States)
2011-2025
University of California, Berkeley
2003-2025
Praj (India)
2017-2024
Savitribai Phule Pune University
2016-2024
Novartis (Switzerland)
2008-2023
Novartis Institutes for BioMedical Research
2008-2023
National Institute of Technology Karnataka
2023
Ginkgo BioWorks (United States)
2021
Stanford University
2019
Wockhardt (India)
2019
Malignant tumors can evade destruction by the immune system attracting immune-suppressive regulatory T cells (Treg) cells. The IKZF2 (Helios) transcription factor plays a crucial role in maintaining function and stability of Treg cells, deficiency reduces tumor growth mice. Here we report discovery NVP-DKY709, selective molecular glue degrader that spares IKZF1/3. We describe recruitment-guided medicinal chemistry campaign leading to NVP-DKY709 redirected degradation selectivity cereblon...
Englerin A is a structurally unique natural product reported to selectively inhibit growth of renal cell carcinoma lines. large scale phenotypic profiling experiment (CLiP) englerin on ¬over 500 well characterized cancer lines showed that inhibits subset tumor from many lineages, not just carcinomas. Expression the TRPC4 cation channel was line feature best correlated with sensitivity A, suggesting hypothesis efficacy target for A. Genetic experiments demonstrate expression both necessary...
Abstract Stimulator of interferon genes (STING) is a dimeric transmembrane adapter protein that plays key role in the human innate immune response to infection and has been therapeutically exploited for its antitumor activity. The activation STING requires high-order oligomerization, which could be induced by binding endogenous ligand, cGAMP, cytosolic ligand-binding domain. Here we report discovery through functional screens class compounds, named NVS-STGs, activate STING. Our cryo-EM...
WD repeat domain 5 (WDR5) is a member of the WD40-repeat protein family that plays critical role in multiple processes. It also prominent target for pharmacological inhibition diseases such as cancer, aging, and neurodegenerative disorders. Interactions between WDR5 various partners are essential sustaining its function. Most drug discovery efforts center on WIN (WDR5 interaction motif) site responsible recruitment to chromatin. Here, we describe novel inhibitors other WBM binding pocket...
Abnormal activation of the Hedgehog (Hh) signaling pathway has been linked to several types human cancers, and development small-molecule inhibitors this represents a promising route toward novel anticancer therapeutics. A cell-based screen performed in our laboratories identified new class Hh inhibitors, 1-amino-4-benzylphthalazines, that act via antagonism Smoothened receptor. variety analogues were synthesized their structure-activity relationships determined. This optimization resulted...
A new fragment-based method for the rapid development of novel and distinct classes nonpeptidic protease inhibitors, Substrate Activity Screening (SAS), is described. This consists three steps: (1) a library N-acyl aminocoumarins with diverse, low molecular weight groups screened to identify substrates using simple fluorescence-based assay, (2) identified aminocoumarin are optimized by analogue synthesis evaluation, (3) converted inhibitors direct replacement known mechanism-based...
A critical component of in silico analysis underdetermined metabolic systems is the identification appropriate objective function. common assumption that cell to maximize growth. This function has been shown be consistent a few limited experimental cases, but may not universally appropriate. Here method presented quantitatively determine most probable function.The genome-scale metabolism Escherichia coli growing on succinate was used as case-study for analysis. Five different functions,...
Recent advancements in instruction-tuned large language models offer new potential for enhancing students' experiences large-scale classes. Deploying LLMs as student-facing assistants, however, presents challenges. Key issues include integrating class-specific content into responses and applying effective pedagogical techniques. This study addresses these challenges through retrieval prompting techniques, focusing on mitigating hallucinations LLM-generated responses, a crucial concern...
Cyclic peptide natural products have evolved to exploit diverse protein targets, many of which control essential cellular processes. Inspired by a series cyclic peptides with partially elucidated structures, we designed synthetic variants ternatin, cytotoxic and anti-adipogenic product whose molecular mode action was unknown. The new ternatin are toward cancer cells, up 500-fold greater potency than itself. Using photo-affinity probe, identify the translation elongation factor-1A ternary...
The identification of highly potent and orally bioavailable GPR39 agonists is reported. Compound 1, found in a phenotypic screening campaign, was transformed into compound 2 with good activity on both the rat human receptor. This further optimized to improve ligand efficiency pharmacokinetic properties yield for potential oral treatment type diabetes. Thus, 3 first agonist (EC50s ≤ 1 nM receptor) that mice robustly induced acute GLP-1 levels.
This study reports an industrially applicable non-sterile xylitol fermentation process to produce from a low-cost feedstock like corn cob hydrolysate as pentose source without any detoxification. Different immobilization matrices/mediums (alginate, polyvinyl alcohol, agarose gel, polyacrylamide, gelatin, and κ-carrageenan) were studied immobilize Candida tropicalis NCIM 3123 cells for production. Amongst this calcium alginate, immobilized produced maximum amount of with titer 11.1 g/L yield...
Receptors based on a tetraphenylporphyrin scaffold bearing different charged and hydrophobic groups have been synthesized. The interactions of these with horse heart cytochrome c were studied by fluorescence spectroscopy. Receptor 4 was identified to be the strongest synthetic receptor (Kd = 20 nM) for c. differences in affinity among receptors reflected dependence number anionic groups.
Abstract A small synthetic library of cyclohexapeptidomimetic calixarenes was prepared to identify disrupters vascular endothelial growth factor (VEGF) binding its receptor that inhibits angiogenesis. From this library, we discovered GFA-116, which potently 125I-VEGF Flk-1 in Flk-1-overexpressing NIH 3T3 cells and human prostate tumor with an IC50 750 nm. This inhibition is highly selective for VEGF 125I- platelet-derived not affected. GFA-116 VEGF-stimulated tyrosine phosphorylation...
RNA viruses are responsible for a variety of illnesses among people, including but not limited to the common cold, flu, HIV, and ebola. Developing new drugs strategies treating diseases caused by these can be an expensive time-consuming process. Mathematical modeling may used elucidate host-pathogen interactions highlight potential targets drug development, as well providing basis optimizing patient treatment strategies. The purpose this work was determine whether genome-scale approach could...
WDR5 is a critical chromatin cofactor of MYC. interacts with MYC through the WBM pocket and hypothesized to anchor its WIN site. Blocking interaction impairs recruitment target genes disrupts oncogenic function in cancer development, thus providing promising strategy for treatment MYC-dysregulated cancers. Here, we describe discovery novel antagonists containing 1-phenyl dihydropyridazinone 3-carboxamide core that was identified from high-throughput screening subsequent structure-based...
This paper focuses on using Large Language Models to support teaching assistants in answering questions large student forums such as Piazza and EdSTEM. Since these are often closely tied specific aspects of the institution, instructor, course delivery, general-purpose LLMs do not directly well this task. We introduce RetLLM-E, a method that combines text-retrieval prompting approaches enable provide precise high-quality answers questions. When presented with question, our system initiates...