Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:6.2.1.1 (ACS)
 78,556 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A primary role of melanin in skin is the prevention of UV-induced nuclear DNA damage to human skin cells, where it serves to screen out harmful UV radiation. Melanin is delivered to keratinocytes in the skin after being excreted as melanosomes from melanocytes. Defects in melanin production in humans can cause diseases, many of which currently lack effective treatments due to their genetic origins (e.g., skin cancer, vitiligo, and albinism). The widespread prevalence of melanin-related diseases and an increasing interest in the performance of various polymeric materials related to melanin necessitates novel synthetic routes for preparing melanin-like materials. In this work, we prepared melanin-like nanoparticles (MelNPs) via spontaneous oxidation of dopamine, as biocompatible, synthetic analogues of naturally occurring melanosomes, and investigated their uptake, transport, distribution, and UV-protective capabilities in human keratinocytes. Critically, we demonstrate that MelNPs are endocytosed, undergo perinuclear aggregation, and form a supranuclear cap, or so-called microparasol in human epidermal keratinocytes (HEKa), mimicking the behavior of natural melananosomes in terms of cellular distribution and the fact that they serve to protect the cells from UV damage.
ACS Cent Sci 2017 Jun 28
PMID:Mimicking Melanosomes: Polydopamine Nanoparticles as Artificial Microparasols. 2869 Oct 67

PF-06651600 was developed as an irreversible inhibitor of JAK3 with selectivity over the other three JAK isoforms. A high level of selectivity toward JAK3 is achieved by the covalent interaction of PF-06651600 with a unique cysteine residue (Cys-909) in the catalytic domain of JAK3, which is replaced by a serine residue in the other JAK isoforms. Importantly, 10 other kinases in the kinome have a cysteine at the equivalent position of Cys-909 in JAK3. Five of those kinases belong to the TEC kinase family including BTK, BMX, ITK, RLK, and TEC and are also inhibited by PF-06651600. Preclinical data demonstrate that inhibition of the cytolytic function of CD8+ T cells and NK cells by PF-06651600 is driven by the inhibition of TEC kinases. On the basis of the underlying pathophysiology of inflammatory diseases such as rheumatoid arthritis, inflammatory bowel disease, alopecia areata, and vitiligo, the dual activity of PF-06651600 toward JAK3 and the TEC kinase family may provide a beneficial inhibitory profile for therapeutic intervention.
ACS Chem Biol 2019 06 21
PMID:PF-06651600, a Dual JAK3/TEC Family Kinase Inhibitor. 3108 93