Ruxolitinib, a JAK1/JAK2 selective inhibitor, ameliorates acute and chronic steroid-refractory GvHD mouse models.

Graft-versus-host disease (GvHD) is a major complication arising in patients undergoing allogenic hematopoietic stem cell transplantation.  We tested ruxolitinib (a selective JAK1/2 inhibitor) efficacy in three different preclinical models of GvHD.  Ruxolitinib, at doses that mimic clinically achievable human JAK/signal transducers and activators of transcription target inhibition, significantly reduced alloreactive T-cell activation and infiltration in the lung and skin, leading to improved outcomes in two experimental models of steroid-refractory acute and chronic GvHD.

Preclinical characterization of itacitinib (INCB039110), a novel selective inhibitor of JAK1, for the treatment of inflammatory diseases.

Pharmacological modulation of the Janus kinase (JAK) family has achieved clinically meaningful therapeutic outcomes for the treatment of inflammatory and hematopoietic diseases. Several JAK1 selective compounds are being investigated clinically to determine their anti-inflammatory potential. We used recombinant enzymes and primary human lymphocytes to assess the JAK1 specificity of itacitinib (INCB039110) and study inhibition of signal transducers and activators of transcription (STAT) signaling.

The Basic Helix-Loop-Helix Gene Nato3 Drives Expression of Dopaminergic Neuron Transcription Factors in Neural Progenitors.

The floor plate of the developing midbrain gives rise to dopaminergic (DA) neurons, an important class of cells involved in Parkinson's disease (PD). Neural progenitors of the midbrain floor plate utilize key genes in transcriptional networks to drive dopamine neurogenesis. Identifying factors that promote dopaminergic neuron transcriptional networks can provide insight into strategies for therapies in PD.