Chemicals

PS48 activates phosphoinositide-dependent protein kinase 1 (PDK1) by binding exclusively to PIF-binding pocket rather than the ATP binding site.References1) A. Stroba et al. “3 5-Diphenylpent-2-enoic Acids as Allosteric Activators of the Protein Kinase PDK1: Structure-Activity Relationships and Thermodynamic Characterization of Binding as Paradigms for PIF-Binding Pocket-Targeting Compounds” J. Med. Chem 2009 52 (15) 4683-46932) L.D. Spate et al. “PS48 can replace bovine serum albumin in pig embryo culture medium and improve in vitro embryo development by phosphorylating AKT” Molecular Reproduction & Development 2015 DOI: 10.1002/mrd.22474.

Hyaluronidases (HAse) are a group of enzymes that degrade Hyaluronan (HA) a linear polysaccharide comprised of a repeating disaccharide of N-acetylglucosamine and D-glucuronic acid. HA is involved in many biological processes including structural support cell migration and tissue turnover. Hyaluronidases are involved in several pathological processes such as bacterial pathogenesis the spreading of toxins/venoms and cancer progression making hyaluronidases a potential pharmacological target. 6-O-Palmitoyl-L-ascorbic acid (Vcpal) is a micromolar HAse inhibitor of both bacterial and mammalian hyaluronidases and it is particularly selective for the Streptococcus agalactiae enzyme.References1) A. Botzki et al. L-Ascorbic Acid 6-Hexadecanoate a Potent Hyaluronidase Inhibitor: X-ray structure and molecular modeling of enzyme-inhibitor complexes. J. Biol. Chem. 2004 279 45990-45997. 2) Spickenreither M. et al. Novel 6-O-acylated vitamin C derivatives as hyaluronidase inhibitors with

HA130 is a boronic acid based inhibitor of the lysoPLD activity of autotaxin (ATX). HA130 is a potent (IC50 = 28 nM) reversible inhibitor which interacts with the oxygen in active site residue T210. HA130 is selective against ATX and does not show any activity against NPP1 alkaline phosphatase phosphodiesterase at concentrations up to 10 microM. In addition proteosomal chymotryptic caspase and typtic activities were not affected. It also showed minimal toxicity against A2058 HEK293T and HepG2 cell lines (TD50 = 105 83 & 2056 µM respectively). Plasma ATX activity was inhibited and circulating LPA levels decreased when administered to mice.References Powered by Bioz See more details on Bioz1) H.M.H.G. Albers et al. “Boronic acid-based inhibitor of autotaxin reveals rapid turnover of LPA in the circulation” Proc. Natl. Acad. Sci. USA 2010 107 7257-7262.2) H.M.H.G. Albers et al. “Discovery and Optimization of Boronic Acid Based Inhibitors of Autotaxin” J.Med. Ch

PF-8380 is a potent autotaxin (ATX) inhibitor (IC50 2.8 nM/101 nM purified enzyme/whole blood). Excessive activity of ATX is associated with numerous inflammatory conditions cancers and other disease. Lysophosphatidic acid (LPA) produced by ATX stimulates cell proliferation through G-protein coupled receptorsLPA1-4. PF-8380 is orally bioavailable and effectively inhibits ATX in vivo reducing LPA levels in serum and at the site of inflammation in a rat arthritis model. Can delivered orally with the "Oral Formulation Vehicle".References Powered by Bioz See more details on BiozGierse J. et al (2010) "A Novel Autotaxin Inhibitor Reduces Lysophosphatidic Acid Levels in Plasma and the Site of Inflammation"> Journal of Pharmacology and Experimental Therapeutics 334(1):310.

This buffer is intended to create aqueous suspensions of organic soluble compounds for oral administration in nonhuman research subjects. The vehicle is formulated with a cellulose compound not metabolized by laboratory rodents.

FTY720 is a structural analog of sphingosine as well as a substrate for sphingosine kinase. The phosphorylated FTY720 acts as a potent agonist at four of the sphingosine-1-phosphate (S1P) receptors (S1P1 S1P3 S1P4 and S1P5). It is a novel immune modulator that prolongs allograft transplant survival in numerous models by inhibiting lymphocyte emigration from lymphoid organs. Animal studies suggest that FTY720 can effectively treat several autoimmune diseases and it has been approved for treating relapsing-remitting multiple sclerosis under the brand name Gilenya® (Fingolimod).Publications Powered by Bioz See more details on Bioz

FTY720P is the bioactive form of the novel immunosuppressive drug fingolimod (FTY720). FTY720 is converted to FTY720P by sphingosine kinase and the (S)-isomer acts as an agonist to four S1P receptors (S1P1 3 4 5) with IC50s of 2.1 5.9 23 and 2.2 nM respectively. The R isomer binds with 5-10 fold lower affinity. FTY720P improves the survival of neonatal rat oligodendrocytes regulates oligodendrocyte progenitor cells differentiation promotes astrocyte migration via extracellular signal-regulated kinase (ERK) signaling. Recently published results indicate involvement of FTY720P in complete viral clearance of persistent infection caused by clone 13 of lymphotic choriomeningitis virus (LCMV).Publications Powered by Bioz See more details on Bioz1. Bucki R. et al. (2010). "Plasma gelsolin modulates cellular response to sphingosine 1-phosphate." Am J Physiol Cell Physiol 299(6): C1516-1523.2. Gu Y. et al. (2011). "Epithelial cell extrusion requires the sphingosine-1-phosphate receptor

To date six types of receptors LPA1-6 have been identified and are responsible for most of the biological activities of LPA. Recent studies on gene targeting in mice and family diseases of these receptors revealed that LPA is involved in various patho-physiological states. LPA antagonists have attracted considerable attention and numerous small molcules having LPA antagonistic activity have been reported. Ki16425 is an antagonist of LPA1 and LPA3 receptors with moderate activity against LPA2.References: Powered by Bioz See more details on Bioz1. Hideo Ohta et al “Ki16425 a Subtype-Selective Antagonist for EDG-Family Lysophosphatidic Acid Receptors” Molecular Pharmacology 2003 166(4) 994-10052. Jing Zhao et al “Lysophosphatidic Acid Receptor 1 antagonist Ki16425 Blunts Abdominal and Systemic Inflammation in a Mouse Model of Peritoneal Sepsis” Translational Research 2015 166(1) 80–88

9-tert-Butyl Doxycycline (9TB) is a Tet On/Off system agonist capable of activating and acting as an inducer for the tetracycline-transactivator (tTA) and reverse tTA (rtTA) and tTA-responsive promoters (Ptets) herein known as the Tet switch. The compound is able to activate the Tet switch with approximately 10-fold greater efficacy especially in lipophilic environments such as the brain and lung and other similar biocompartments. 9TB is freely soluble in water and can be administered IV IP and in the drinking water of experimental animals allowing for ready dosing. 9TB also has found use in studying hypoxia-regulated gene expression on cell survival using the tetracycline-inducible (tet-on) system where exposure to the inducing ligand doxycycline (dox) inhibited caspase-3 cleavage in mitochondria in Publications Powered by Bioz See more details on Bioz1) Zhu P. et al. “Silencing and Un-silencing of Tetracycline-Controlled Genes in Neurons” PLoS ONE. 2007; 2(6): e533.2)