In Nature Communications, Zhang et al. show that DJ001, a selective allosteric inhibitor of protein tyrosine phosphatase sigma (PTPσ), promotes hematopoietic stem cell (HSC) regeneration. Treatment of irradiated human HSCs with DJ001 promoted the regeneration of HSCs capable of multilineage in vivo repopulation. For a comprehensive portfolio of small molecule stem cell effectors visit https://focusbiomolecules.com/stem-cells-main/.
In a fascinating paper just out in Cell Metabolism, Mathias Wenes and coworkers found that the mitochondrial pyruvate carrier (MPC) regulates memory T cell differentiation and antitumor activity. They showed that CAR T cells treated with UK-5099, a small molecule MPC inhibitor, resulted in superior and long lasting antitumor activity. Thus CAR T cells manufactured …
CHIR-99021 is another popular tool for stem cell maintenance which increases cell survival and proliferation. It is a GSK3β inhibitor, and Komiya et al. used CHIR-99021 from Focus Biomolecules to generate liver organoids for establishment of a novel genotoxicity assay system.
The compound Y-27632 inhibits ROCK family kinases and is a very popular tool for embryonic stem cell (ESC) maintenance because it enhances survival and proliferation in culture. Ray et al. used Y-27632 dihydrochloride from Focus Biomolecules to maintain human embryonic stem cell-derived cardiomyocytes in their March 2022 paper “Membrane repair triggered by cholesterol-dependent cytolysins is …
Ferroptosis is a type of cell death caused by iron-dependent peroxidation of phospholipids and is important for proper function of tumor suppression, immune surveillance, and the central nervous system. A recent paper by Wang et al. reviews the role of ferroptosis in suppressing tumor progression, and discusses how small molecule inducers of ferroptosis might be …
Disrupting N-glycan expression on tumor cells enhanced CAR T cell efficacy. Greco et al. treated mice with 2-deoxy-D-glucose (Focus Cat.# 10-2171), a glucose analog, disrupting N-glycan expression on the surface of pancreatic adenocarcinoma cells. This treatment boosted CAR T cell activity leading to improved killing of pancreatic, lung, ovary and bladder tumors. These findings identify …
The FDA has approved the use of olaparib (Focus Cat.# 10-2154) as adjuvant treatment for patients with BRCA-mutated HER-2 negative high-risk early breast cancer that were previously treated with chemotherapy before or after surgery. Olaparib is a highly potent and selective PARP-inhibitor with IC50 values of 5 nM and 1 nM for PARP-1 and PARP-2, …
In a paper just out in Cell, Marco De Giovanni et al. at UCSF demonstrated that 5-hydroxyindoleacetic acid (5-HIAA), a platelet serotonin metabolite, acts as a physiological agonist at the orphan receptor GPR35 (G protein-coupled receptor 35). Activated GPR35 promotes neutrophil migration and recruitment to sites of inflammation and bacterial clearance. The study sheds light …
NSD2 (nuclear receptor-binding SET domain-containing 2) is a methyltransferase that specifically targets histone H3 at Lysine 36 (making it a H3K36me2 in chromatin remodeling nomenclature). It binds target histones via its two PWWP1 domains, and this interaction is potently antagonized (IC50 = 104 nM) by the new small molecule UNC6934 (Focus Cat# 10-4119).
In a PNAS paper just out Yu and coworkers showed that the small molecule NEDD8-activating enzyme (NAE) inhibitor MLN4924 (pevonedistat, Focus Cat# 10-1311) reduces ischemic brain injury in a mouse model. The study found that neddylation increases in the acute phase following ischemic stroke, and treatment with MLN4924 protects against the resulting inflammation and blood–brain …