A potent peptide-steroid conjugate accumulates in cartilage and reverses arthritis without evidence of systemic corticosteroid exposure.

On-target, off-tissue toxicity limits the systemic use of drugs that would otherwise reduce symptoms or reverse the damage of arthritic diseases, leaving millions of patients in pain and with limited physical mobility. We identified cystine-dense peptides (CDPs) that rapidly accumulate in cartilage of the knees, ankles, hips, shoulders, and intervertebral discs after systemic administration. These CDPs could be used to concentrate arthritis drugs in joints.

Inhibition of CDK4/6 by Palbociclib Significantly Extends Survival in Medulloblastoma Patient-Derived Xenograft Mouse Models.

Bioinformatics analysis followed by studies in patient-derived xenograft (PDX) models were used to identify and validate CDK 4/6 inhibition as an effective therapeutic strategy for medulloblastoma, particularly group 3 -amplified tumors that have the worst clinical prognosis. A protein interaction network derived from a mutagenesis model of medulloblastoma was used to identify potential novel therapeutic targets. The top hit from this analysis was validated using PDX models of medulloblastoma implanted subcutaneously in the flank and orthotopically in the cerebellum of mice.

Identification of genetic variants of human cytochrome P450 2D6 with impaired mitochondrial targeting.

Human cytochrome P450 2D6 (CYP2D6) is responsible for the metabolism of approximately 20% of drugs in common clinical use. The CYP2D6 gene locus is highly polymorphic. Many of the polymorphisms have been shown to be clinically relevant and can account for inter-individual differences in the metabolism of specific drugs.

Human liver mitochondrial cytochrome P450 2D6--individual variations and implications in drug metabolism.

Constitutively expressed human cytochrome P450 2D6 (CYP2D6; EC 1.14.14.