LP-118 is a novel B-cell lymphoma 2 / extra-large inhibitor that demonstrates efficacy in models of venetoclaxresistant chronic lymphocytic leukemia.

Patients with chronic lymphocytic leukemia (CLL) respond well to initial treatment with the B-cell lymphoma 2 (BCL2) inhibitor venetoclax. Upon relapse, they often retain sensitivity to BCL2 targeting, but durability of response remains a concern. We hypothesize that targeting both BCL2 and B-cell lymphoma-extra large (BCLXL) will be a successful strategy to treat CLL, including for patients who relapse on venetoclax.

Genome-wide identification and expression analysis of WRKY transcription factors in pearl millet (Pennisetum glaucum) under dehydration and salinity stress.

Background: Plants have developed various sophisticated mechanisms to cope up with climate extremes and different stress conditions, especially by involving specific transcription factors (TFs). The members of the WRKY TF family are well known for their role in plant development, phytohormone signaling and developing resistance against biotic or abiotic stresses. In this study, we performed a genome-wide screening to identify and analyze the WRKY TFs in pearl millet (Pennisetum glaucum; PgWRKY), which is one of the most widely grown cereal crops in the semi-arid regions.

Fabrication of biobeads expressing heavy metal-binding protein for removal of heavy metal from wastewater.

Heavy metals, being toxic in nature, are one of the most persistent problems in wastewater. Unabated discharge of large amount of heavy metals into water bodies are known to cause several environmental and health impacts. Biological remediation processes like microbial remediation and phytoremediation are proved to be very effective in the reduction of heavy metal pollutants in wastewater.

Phenothiazines and phenoxazines: as electron transfer mediators for ferritin iron release.

Intracellular ferritin stores iron as ferrihydrite and releases it for various cellular metabolic activities. The reductive approach, one of the possible mechanisms of iron mobilization from ferritin nanocages, requires electron transfer (ET) from reducing agent(s) to the protein encapsulated iron. In vitro, the rate of ET from the physiological reducing agent, NADH, to mineralized ferritin is very slow resulting in a smaller amount of iron release.

Pharmacophore modeling and molecular dynamics approach to identify putative DNA Gyrase B inhibitors for resistant tuberculosis.

One of the major mechanisms followed by the therapeutic agents to target the causative organism of TB, mycobacterium tuberculosis (Mtb), involves disruption of the replication cycle of the pathogen DNA. The process involves two steps that occur simultaneously, ie, breakage and reunion of DNA at gyrase A (GyrA) domain and ATP hydrolysis at gyrase B (GyrB) domain. Current therapy for multi-drug resistant TB involves FDA approved, Fluoroquinolone-based antibiotics, which act by targeting the replication process at GyrA domain.

Releasing iron from ferritin protein nanocage by reductive method: The role of electron transfer mediator.

Background: Ferritin detoxifies excess of free Fe(II) and concentrates it in the form of ferrihydrite (FeO·xHO) mineral. When in need, ferritin iron is released for cellular metabolic activities. However, the low solubility of Fe(III) at neutral pH, its encapsulation by stable protein nanocage and presence of dissolved O limits in vitro ferritin iron release.

Comparative molecular dynamics studies of heterozygous open reading frames of DNA polymerase eta (η) in pathogenic yeast Candida albicans.

Genomic instability in Candida albicans is believed to play a crucial role in fungal pathogenesis. DNA polymerases contribute significantly to stability of any genome. Although Candida Genome database predicts presence of S.

S95C substitution in CuZn-SOD of Ipomoea carnea: impact on the structure, function and stability.

Superoxide dismutase (SOD) in general is a unique homo-dimeric enzyme that can scavenge toxic superoxide radicals by dismutation reaction. In IcSOD (Ipomoea carnea SOD), the presence of cysteine (Cys) plays an essential role in protein behaviour. This study analysed the role of Cys in modulating the stability and kinetic properties of IcSOD.

Overexpression of human peroxisomal enoyl-CoA delta isomerase2 HsPECI2, an ortholog of bamboo expressed during gregarious flowering alters salinity stress responses and polar lipid content in tobacco.

Peroxisomal enoyl-CoA delta isomerase2 (PECI2) is one of the key enzymes that has critical role in lipid metabolism and plant development during salt stress. Seven out of ten tobacco plants overexpressing human PECI2 (HsPECI2) with PTS1-sequence showed hypersensitivity to salt. Under salt-stress, T2 transformed plants (HsPECI2) displayed reduced primary root, delayed shoot-growth, and visibly smaller rosette leaves turning pale yellow as compared to the pKYLX71 vector control plant.

Doxorubicin inhibits E. coli division by interacting at a novel site in FtsZ.

The increase in antibiotic resistance has become a major health concern in recent times. It is therefore essential to identify novel antibacterial targets as well as discover and develop new antibacterial agents. FtsZ, a highly conserved bacterial protein, is responsible for the initiation of cell division in bacteria.

Molecular modeling and identification of novel glucokinase activators through stepwise virtual screening.

The glucose phosphorylating enzyme glucokinase (GK) is a 50kD monomeric protein having 465 amino acids. It maintains glucose homeostasis inside cells, acts as a glucose sensor in pancreatic β-cells and as a rate controlling enzyme for hepatic glucose clearance and glycogen synthesis. It has two binding sites, one for binding d-glucose and the other for a putative allosteric activator named glucokinase activator (GKA).

Development of constrained tamoxifen mimics and their antiproliferative properties against breast cancer cells.

An efficient synthesis of a new series of tamoxifen mimics is described by employing iodine catalyzed ipsocyclization strategy followed by Suzuki coupling. A molecular docking studies of the synthesized compounds 11a-n and 12 in estrogen receptor (ER-α) showed that the scaffolds are fitting well in the groove, thereby suggesting them as promising antiproliferative agents for estrogen dependent breast cancer lines. All compounds were tested in vitro against breast cancer cell lines-ER positive, MCF-7; ER negative, MDA-MB-231; and control mammary epithelial cells, MEpiC.