CD8+T cell responsiveness to anti-PD-1 is epigenetically regulated by Suv39h1 in melanomas.

Tumor-infiltrating CD8 + T cells progressively lose functionality and fail to reject tumors. The underlying mechanism and re-programing induced by checkpoint blockers are incompletely understood. We show here that genetic ablation or pharmacological inhibition of histone lysine methyltransferase Suv39h1 delays tumor growth and potentiates tumor rejection by anti-PD-1.

Odiparcil, a potential glycosaminoglycans clearance therapy in mucopolysaccharidosis VI-Evidence from in vitro and in vivo models.

Mucopolysaccharidoses are a class of lysosomal storage diseases, characterized by enzymatic deficiency in the degradation of specific glycosaminoglycans (GAG). Pathological accumulation of excess GAG leads to multiple clinical symptoms with systemic character, most severely affecting bones, muscles and connective tissues. Current therapies include periodic intravenous infusion of supplementary recombinant enzyme (Enzyme Replacement Therapy-ERT) or bone marrow transplantation.

ADX71743, a potent and selective negative allosteric modulator of metabotropic glutamate receptor 7: in vitro and in vivo characterization.

Metabotropic glutamate receptor 7 (mGlu(7)) has been suggested to be a promising novel target for treatment of a range of disorders, including anxiety, post-traumatic stress disorder, depression, drug abuse, and schizophrenia. Here we characterized a potent and selective mGlu(7) negative allosteric modulator (NAM) (+)-6-(2,4-dimethylphenyl)-2-ethyl-6,7-dihydrobenzo[d]oxazol-4(5H)-one (ADX71743). In vitro, Schild plot analysis and reversibility tests at the target confirmed the NAM properties of the compound and attenuation of L-(+)-2-amino-4-phosphonobutyric acid-induced synaptic depression confirmed activity at the native receptor.

Docetaxel (Taxotere) is not metabolized by recombinant human CYP1B1 in vitro, but acts as an effector of this isozyme.

The objective of this study was to determine whether recombinant human cytochrome P450 1B1 (rhCYP1B1) metabolizes the anticancer agent docetaxel (Taxotere) in vitro. First, the catalytic activities of Supersomes-expressed rhCYP1B1 toward 17beta-estradiol and of rhCYP3A4 toward docetaxel in our conditions were determined. Second, [(14)C]docetaxel at 0.