Anti-Protein Tyrosine Phosphatase 69D Monoclonal antibody, clone 3F11

The cure rate of childhood acute lymphoblastic leukemia (ALL) has exceeded 90% in some contemporary clinical trials. However, the dose intensity of conventional chemotherapy has been pushed to its limit. Further improvement in outcome will need to rely more heavily on molecular therapeutic as well as immuno-and cellular-therapy approaches together with precise risk stratification. Children withETV6-RUNX1or hyperdiploid > 50 ALL who achieve negative minimal residual disease during early remission induction are suitable candidates for reduction in treatment. Patients with Philadelphia chromosome (Ph)-positive or Ph-like ALL with ABL-class fusion should be treated with dasatinib. BH3 profiling and other preclinical methods have identified several high-risk subtypes, such as hypodiplod, early T-cell precursor, immature T-cell,KMT2A-rearranged, Ph-positive and TCF-HLF-positive ALL, that may respond to BCL-2 inhibitor venetoclax. There are other fusions or mutations that may serve as putative targets, but effective targeted therapy has yet to be established. For other high-risk patients or poor early treatment responders who do not have targetable genetic lesions, current approaches that offer hope include blinatumomab, inotuzumab and CAR-T cell therapy for B-ALL, and daratumumab and nelarabine for T-ALL. With the expanding therapeutic armamentarium, we should start focus on rational combinations of targeted therapy with non-overlapping toxicities.

Background Traditionally, Ficus benghalensisL. is used to treat metabolic disorders and is also recorded in the Ayurvedic pharmacopeia of India. The present study aimed to evaluate the anti-diabetic property of hydroalcoholic extract/fraction(s) ofF. benghalensis L. bark via in silico, in vitro,and ex vivo approach. Methods Enzyme inhibitory activity, glucose uptake in rat hemidiaphragm, and glucose permeability, and adsorption assays were performed using in vitro and ex vivo methods as applicable. Further, the PASS was used to identify the probable lead enzyme inhibitors. The presence of predicted enzyme inhibitors was confirmed via the LC-MS. Similarly, the docking of ligands with respective targets was performed using autodock4.0. Results Flavonoids rich fraction possessed the highest alpha-amylase, and alpha-glucosidase inhibitory activity followed by maximum efficacy for glucose uptake in rat hemidiaphragm. Similarly, the hydroalcoholic extract showed the highest efficacy to inhibit glucose diffusion. Likewise, 3,4-dihydroxybenzoic acid was predicted for the highest pharmacological activity for alpha-amylase, ursolic acid for PTP1B, and apigenin for alpha-glucosidase inhibition respectively. The LC-MS analysis also identified the presence of the above hit molecules in the hydroalcoholic extract. Conclusion The analogs of 3,4-dihydroxybenzoic acid, apigenin, and ursolic acid could be the choice of lead hits as the alpha-amylase, alpha-glucosidase, and PTP1B inhibitors respectively. Additionally, the majority of secondary metabolites from the hydroalcoholic extract ofF. benghalensismay be involved in enhancing the glucose uptake to support the process of glycogenesis.