A5065784113- Cancer Immunotherapy and Biomarkers
- Protein Degradation and Inhibitors
- Cytokine Signaling Pathways and Interactions
- Virus-based gene therapy research
- Peptidase Inhibition and Analysis
- Acute Myeloid Leukemia Research
- Cancer Mechanisms and Therapy
- CAR-T cell therapy research
- Advanced Breast Cancer Therapies
- Chromatin Remodeling and Cancer
- Cancer-related Molecular Pathways
- RNA Interference and Gene Delivery
- Click Chemistry and Applications
- Drug Transport and Resistance Mechanisms
- Ubiquitin and proteasome pathways
- Immunotherapy and Immune Responses
- Lung Cancer Research Studies
- Fibroblast Growth Factor Research
- Synthesis and biological activity
- Histone Deacetylase Inhibitors Research
- Viral Infectious Diseases and Gene Expression in Insects
- HIV/AIDS drug development and treatment
- Cancer Research and Treatments
- Cancer therapeutics and mechanisms
- Cancer, Hypoxia, and Metabolism
Aurigene Discovery Technologies (India)
2015-2024
Medigene (Germany)
2024
University of Agricultural Sciences, Bangalore
1978-2020
University of Agricultural Sciences, Dharwad
2011
PROTO Manufacturing (United States)
2001
National Institutes of Health
1996-2000
MRC Laboratory of Molecular Biology
1996-2000
National Cancer Institute
1996-1999
National Institute of Allergy and Infectious Diseases
1998
University of Kansas Medical Center
1993-1995
The FDA approved HIV-1 protease inhibitors, ritonavir, saquinavir, and indinavir, are very effective in inhibiting replication, but their long-term efficacy is unknown. Since vivo depends on access of these drugs to intracellular sites where replicates, we determined whether inhibitors recognized by the MDR1 multidrug transporter (P-glycoprotein, or P-gp), thereby reducing accumulation. In vitro studies isolated membrane preparations from insect cells infected with MDR1-expressing...
Abstract The switch/sucrose non-fermentable (SWI/SNF) complex has a crucial role in chromatin remodelling 1 and is altered over 20% of cancers 2,3 . Here we developed proteolysis-targeting chimera (PROTAC) degrader the SWI/SNF ATPase subunits, SMARCA2 SMARCA4, called AU-15330. Androgen receptor (AR) + forkhead box A1 (FOXA1) prostate cancer cells are exquisitely sensitive to dual SMARCA4 degradation relative normal other cell lines. rapidly compacts cis -regulatory elements bound by...
Abstract Small molecule immune checkpoint inhibitors targeting PD-1 and other pathways may offer advantages including ease of dosing, ability to manage immune-related adverse events (irAEs) due their shorter pharmacokinetic exposure opportunity target more than one pathway for improving efficacy. Here we describe the identification characterization CA-170, an amino acid inspired small inhibitor PD-L1 VISTA derived from interface PD-L1. CA-170 exhibited potent rescue proliferation effector...
Human P-glycoprotein (Pgp) confers multidrug resistance to cancer cells by ATP-dependent extrusion of a great many structurally dissimilar hydrophobic compounds. The manner in which Pgp recognizes these different substrates is unknown. protein shows internal homology between its N- and C-terminal halves, each comprised six putative transmembrane helices consensus ATP binding/utilization site. Photoactive derivatives certain specifically label two regions, one on half the protein. In this...
Dengue virus type 2, a member of the family Flaviviridae, encodes single polyprotein precursor consisting 3391 amino acid residues that is processed to at least 10 mature proteins by host and viral proteases. The NS3 protein contains domain commonly found in cellular serine proteinases cooperation with NS2B involved processing. In addition, NS5 contain conserved motifs several RNA helicases RNA-dependent polymerases, respectively. Both enzymatic activities have been suggested be replication....
Previously we reported production of an extracellular lignin-inducible peroxidase by Streptomyces viridosporus (M. Ramachandra, D.L. Crawford, and A.L. Pometto III, Appl. Environ. Microbiol. 53:2754-2760, 1987). This was shown to oxidize 3,4-dihydroxyphenylalanine, 2,4-dichlorophenol, homoprotocatechuic acid, caffeic N,N,N',N'-tetramethylphenylenediamine found in higher than normal levels strains enhanced for lignocellulose degradation. In the present study, used a pure enzyme preparation...
Human P-glycoprotein (Pgp), a plasma membrane protein that confers multidrug resistance, functions as an ATP-dependent drug efflux pump. Pgp contains two ATP binding/utilization sites and exhibits ATPase activity is stimulated in the presence of substrates modulating agents. The mechanism coupling hydrolysis to transport not known. To understand role binding, it necessary develop methods for purifying reconstituting retains properties including stimulation by known extent similar native...
Mutations in the SF3B1 splicing factor are commonly seen myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML), yet specific oncogenic pathways activated by mis-splicing have not been fully elucidated. Inflammatory immune shown to play roles pathogenesis of MDS, though exact mechanisms their activation mutant cases well understood.RNA-seq data from samples was analyzed functional interleukin-1 receptor-associated kinase 4 (IRAK4) isoforms were determined. Efficacy IRAK4 inhibition...
The POU2F3-POU2AF2/3 transcription factor complex is the master regulator of tuft cell lineage and cell-like small lung cancer (SCLC). Here, we identify a specific dependence POU2F3 molecular subtype SCLC (SCLC-P) on activity mammalian switch/sucrose non-fermentable (mSWI/SNF) chromatin remodeling complex. Treatment SCLC-P cells with proteolysis targeting chimera (PROTAC) degrader mSWI/SNF ATPases evicts its coactivators from attenuates downstream signaling. B malignancies which are...
The wild-type ligninolytic actinomycete Streptomyces viridosporus T7A and two genetically manipulated strains with enhanced abilities to produce a water-soluble lignin degradation intermediate, an acid-precipitable polymeric (APPL), were grown on lignocellulose in solid-state fermentation cultures. Culture filtrates periodically collected, analyzed for APPL, assayed extracellular lignocellulose-catabolizing enzyme activities. Isoenzymes by polyacrylamide gel electrophoresis activity staining...
The extract from Mitragyna speciosa has been widely used as an opium substitute, mainly due to its morphine-like pharmacological effects. This study investigated the effects of M. alkaloid (MSE) on human recombinant cytochrome P450 (CYP) enzyme activities using a modified Crespi method. As compared with liquid chromatography-mass spectrometry method, this method shown be fast and cost-effective way perform CYP inhibition studies. results indicated that MSE most potent inhibitory effect...
Human P-glycoprotein (P-gp) is a cell surface drug efflux pump that contains two nucleotide binding domains (NBDs). Mutations were made in each of the Walker B consensus motifs NBDs at positions D555N and D1200N, thought to be involved Mg2+ binding. Although mutant wild-type P-gps expressed equivalently bound analogue [125I]iodoarylazidoprazosin ([125I]IAAP) comparably, neither proteins was able transport fluorescent substrates nor had detectable basal drug-stimulated ATPase activities. The...
Human P-glycoprotein (P-gp), an ATP-dependent efflux pump responsible for cross-resistance of human cancers to a variety lipophilic compounds, is composed two homologous halves, each containing six transmembrane domains and ATP-binding/utilization domain. To determine whether site can hydrolyze ATP simultaneously, we used orthovanadate (Vi)-induced ADP-trapping technique (P-gp.MgADP.Vi). In analogy with other ATPases, photochemical peptide bond cleavage reaction occurs within the Walker A...
Pioneering success of antibodies targeting immune checkpoints such as PD-1 and CTLA4 has opened novel avenues for cancer immunotherapy. Along with impressive clinical activity, severe immune-related adverse events (irAE) due to the breaking self-tolerance are becoming increasingly evident in antibody-based approaches. As a strategy better manage effects, we set out discover an antagonist signaling pathway shorter pharmacokinetic profile. Herein, describe peptide NP-12 that displays...
Small molecule potent IRAK4 inhibitors from a novel bicyclic heterocycle class were designed and synthesized based on hits identified Aurigene's compound library. The advanced lead compound, CA-4948, demonstrated good cellular activity in ABC DLBCL AML cell lines. Inhibition of TLR signaling leading to decreased IL-6 levels was also observed whole blood assays. CA-4948 moderate high selectivity panel 329 kinases as well exhibited desirable ADME PK profiles including oral bioavailability...
The MDR1 multidrug transporter P-gp (P-glycoprotein) is an efflux pump that extrudes diverse hydrophobic drugs and peptides from cells. Since the entry of HIV-1 into cells involves initial interaction viral gp41 peptide with plasma membrane, a potential effect on infectivity was explored. Virus production greatly decreased when overexpressed at surface continuous CD4(+) human T-leukemic cell line (12D7) infected HIV-1(NL4-3), T-tropic molecular clone HIV-1. overexpression did not...
SUMMARY The POU2F3-POU2AF2/3 (OCA-T1/2) transcription factor complex is the master regulator of tuft cell lineage and cell-like small lung cancer (SCLC). Here, we found that POU2F3 molecular subtype SCLC (SCLC-P) exhibits an exquisite dependence on activity mammalian switch/sucrose non-fermentable (mSWI/SNF) chromatin remodeling complex. SCLC-P lines were sensitive to nanomolar levels a mSWI/SNF ATPase proteolysis targeting chimera (PROTAC) degrader when compared other subtypes SCLC. its...