Publications by authors named "Adi Narayana Reddy Poli"
Article Synopsis
- PDAC is the most common and lethal pancreatic cancer, marked by high levels of HSP70, which relates to poor patient outcomes and aggressive tumor behavior.
- HSP70's overexpression in PDAC disrupts mitochondrial function and promotes cancer cell survival, while its inhibition leads to mitochondrial dysfunction and programmed cell death.
- Targeting HSP70, especially in combination with autophagy inhibitors like hydroxychloroquine, could be a promising strategy for treating HSP70-driven PDAC.
Article Synopsis
- Ovarian cancer poses a significant health risk and has limited treatment options, largely due to an immunosuppressive tumor microenvironment driven by tumor-associated macrophages (TAMs).
- Targeting the retinoblastoma protein (Rb) through its LxCxE cleft pocket induces cell death in TAMs via ER stress and other death pathways, leading to improved T cell infiltration and reduced cancer progression in vivo.
- The study reveals that higher Rb expression in TAMs correlates with worse outcomes for ovarian cancer patients, suggesting that targeting Rb could reshape the tumor microenvironment and enhance the effectiveness of immunotherapy.
Unlabelled: Chemical prototypes with broad-spectrum antiviral activity are important toward developing new therapies that can act on both existing and emerging viruses. Binding of the SARS-CoV-2 spike protein to the host angiotensin-converting enzyme 2 (ACE2) receptor is required for cellular entry of SARS-CoV-2. Toward identifying new chemical leads that can disrupt this interaction, including in the presence of SARS-CoV-2 adaptive mutations found in variants like omicron that can circumvent vaccine, immune, and therapeutic antibody responses, we synthesized 5-chloro-3-(2-(2,4-dinitrophenyl)hydrazono)indolin-2-one (HL) from the condensation reaction of 5-chloroisatin and 2,4-dinitrophenylhydrazine in good yield.
View Article and Find Full Text PDF, the causative agent of Human African Trypanosomiasis (HAT) and animal trypanosomiases, cycles between a bloodstream form in mammals and a procyclic form in the gut of its insect vector. We previously discovered that the human bromodomain inhibitor I-BET151 causes transcriptome changes that resemble the transition from the bloodstream to the procyclic form. In particular, I-BET151 induces replacement of variant surface glycoprotein (VSG) with procyclin protein.
View Article and Find Full Text PDFInhibition of the BCL6 BTB domain results in killing Diffuse Large B-cell Lymphoma (DLBL) cells, reducing the T-cell dependent germinal center (GC) reaction in mice, and reversing GC hyperplasia in nonhuman primates. The available BCL6 BTB-specific inhibitors are poorly water soluble, thus, limiting their absorption in vivo and our understanding of therapeutic strategy targeting GC. We synthesized a prodrug (AP-4-287) from a potent BCL6 BTB inhibitor (FX1) with improved aqueous solubility and pharmacokinetics (PK) in mice.
View Article and Find Full Text PDFThe protein chaperone HSP70 is overexpressed in many cancers including colorectal cancer, where overexpression is associated with poor survival. We report here the creation of a uniquely acting HSP70 inhibitor (HSP70i) that targets multiple compartments in the cancer cell, including mitochondria. This inhibitor was mitochondria toxic and cytotoxic to colorectal cancer cells, but not to normal colon epithelial cells.
View Article and Find Full Text PDFBackground: The BTB domain of B-cell lymphoma 6 (BCL6) protein was identified as a therapeutic target for B-cell lymphoma. This study compared the pharmacokinetics (PK) of the BCL6 BTB inhibitor (FX1) between mice and macaques, as well as evaluating its lymphoid suppressive effect in uninfected macaques with lymphoid hyperplasia.
Materials And Methods: Eight uninfected adult Indian rhesus macaques (Macaca mulatta) were used in the study, four animals carrying lymphoid tissue hyperplasia.