Pharmacological characterization of dopamine, norepinephrine and serotonin release in the rat prefrontal cortex by neuronal nicotinic acetylcholine receptor agonistsTadimeti S Rao
Merck Research Laboratories, 3535 General Atomics Court, San Diego, CA 92121, USA
Brain Res 990:203-8. 2003
..The differences between nicotinic agonist induced catecholamine and serotonin release suggest involvement of distinct nAChRs...
Identification of KD5170: a novel mercaptoketone-based histone deacetylase inhibitorJoseph E Payne
Department of Chemistry, Kalypsys, Inc, 10420 Wateridge Circle, San Diego, CA 92121, USA
Bioorg Med Chem Lett 18:6093-6. 2008
..KD5170 exhibits robust and sustained histone H3 hyperacetylation in HCT-116 xenograft tumors following single oral or i.v. dose and inhibition of tumor growth following chronic dosing...
- Pharmacological characterization of (S)-(2)-5-ethynyl-3-(1-methyl-2-pyrrolidinyl)pyridine HCl (SIB-1508Y, Altinicline), a novel nicotinic acetylcholine receptor agonist
Tadimeti S Rao
Merck Research Laboratories, 3535 General Atomics Court, San Diego, CA 92121, USA
Brain Res 1234:16-24. 2008
..In summary, the abilities of SIB-1508Y to release multiple neurotransmitters in distinct brain regions may contribute to its behavioral profile...
- In vivo pharmacological characterization of (+/-)-4-[2-(1-methyl-2-pyrrolidinyl)ethyl]thiophenol hydrochloride (SIB-1553A), a novel cholinergic ligand: microdialysis studies
Tadimeti S Rao
Merck Research Laboratories, 3535 General Atomics Court, San Diego, CA 92121, USA
Brain Res 986:71-81. 2003
..Due to the proposed role of cholinergic pathways in learning and memory, the neurochemical profile of SIB-1553A suggests a potential for it to treat cognitive dysfunction...
- Discovery of dual inducible/neuronal nitric oxide synthase (iNOS/nNOS) inhibitor development candidate 4-((2-cyclobutyl-1H-imidazo[4,5-b]pyrazin-1-yl)methyl)-7,8-difluoroquinolin-2(1H)-one (KD7332) part 2: identification of a novel, potent, and selective
Joseph E Payne
Department of Chemistry, Kalypsys, Inc, 10420 Wateridge Circle, San Diego, California 92121, USA
J Med Chem 53:7739-55. 2010
..Further 42 did not affect motor coordination up to doses of 1000 mg/kg, demonstrating a wide therapeutic margin...
- Discovery of inducible nitric oxide synthase (iNOS) inhibitor development candidate KD7332, part 1: Identification of a novel, potent, and selective series of quinolinone iNOS dimerization inhibitors that are orally active in rodent pain models
Celine Bonnefous
Department of Chemistry, Kalypsys Inc, 10420 Wateridge Circle, San Diego, CA 92121, USA
J Med Chem 52:3047-62. 2009
..Following oral dosing, compounds 12 and 42 gave a statistical reduction in pain behaviors in the mouse formalin model, while 12 also statistically reduced neuropathic pain behaviors in the chronic constriction injury (Bennett) model...
- Sphingosine 1-phosphate receptor agonists attenuate relapsing-remitting experimental autoimmune encephalitis in SJL mice
Michael Webb
Molecular Neuroscience Laboratory, Merck Research Laboratories, 3535 General Atomics Court, San Diego, CA 92121, USA
J Neuroimmunol 153:108-21. 2004
..EAE produced by adoptively transferring lymph node cells from immunized mice to naïve hosts is similarly ameliorated by FTY-P. Treatment with FTY-P is accompanied by a dose-responsive peripheral lymphopoenia...
- Pharmacological characterization of KLYP961, a dual inhibitor of inducible and neuronal nitric-oxide synthases
Kent T Symons
Department of Biology, Kalypsys Inc, San Diego, California, USA
J Pharmacol Exp Ther 336:468-78. 2011
..o.) and a greater potency than gabapentin. In summary, KLYP961 represents an ideal tool with which to probe the physiological role of NO derived from iNOS and nNOS in human pain and inflammatory states...
- Growth factor pre-treatment differentially regulates phosphoinositide turnover downstream of lysophospholipid receptor and metabotropic glutamate receptors in cultured rat cerebrocortical astrocytes
Tadimeti S Rao
Merck Research Laboratories San Diego, 3535 General Atomics Court, Bldg 1, San Diego, CA 92121, USA
Int J Dev Neurosci 22:131-5. 2004
....
- Pharmacological characterization of SIB-1663, a conformationally rigid analog of nicotine
Tadimeti S Rao
Merck Research Laboratories, 3535 General Atomics Court, San Diego, CA 92121, USA
Brain Res 1003:42-53. 2004
..These data indicate that SIB-1663, a conformationally restricted analog of NIC, with distinct nAChR subtype selectivity from NIC exhibits contrasting pharmacology with some of its in vivo actions involving nAChRs...
- Identification and SAR of selective inducible nitric oxide synthase (iNOS) dimerization inhibitors
Timothy C Gahman
Department of Medicinal Chemistry, Kalypsys Inc, 10420 Wateridge Circle, San Diego, CA 92121, USA
Bioorg Med Chem Lett 21:6888-94. 2011
....
- In vitro pharmacological characterization of (+/-)-4-[2-(1-methyl-2-pyrrolidinyl)ethyl]thio]phenol hydrochloride (SIB-1553A), a nicotinic acetylcholine receptor ligand
Tadimeti S Rao
Merck Research Laboratories, 3535 General Atomics Court, San Diego, CA 92121, USA
Brain Res 981:85-98. 2003
..SIB-1553A did not inhibit rat brain cholinesterase for up to 1 mM. Multiple receptor affinities and release of several neurotransmitters may underlie the cognitive-enhancing effects of SIB-1553A documented in rodent and primate models...
- KLYP956 is a non-imidazole-based orally active inhibitor of nitric-oxide synthase dimerization
Kent T Symons
Department of Biology, Kalypsys Inc, San Diego, CA, USA
Mol Pharmacol 76:153-62. 2009
..KLYP956 thus represents the first nonimidazole-based inhibitor of iNOS and nNOS dimerization and provides a novel pharmaceutical alternative to previously described substrate competitive inhibitors...
- Lysolecithin induces demyelination in vitro in a cerebellar slice culture system
Eric Birgbauer
Department of Neurobiology, Merck Research Laboratories, San Diego, California, USA
J Neurosci Res 78:157-66. 2004
..Lysolecithin thus induces demyelination in an in vitro organotypic cerebellar slice culture system, providing a model system for studying myelination, demyelination, and remyelination in vitro...
- Microglial activation state and lysophospholipid acid receptor expression
Chui-Se Tham
Molecular Neuroscience Laboratory, Merck Research Laboratories, 3535 General Atomics Court, San Diego, CA 92121, USA
Int J Dev Neurosci 21:431-43. 2003
..The levels of mRNA of LPA1 and S1P receptors was reduced by overnight exposure to S1P, while the same treatment significantly up-regulated the level of LPA3 mRNA...
- KD5170, a novel mercaptoketone-based histone deacetylase inhibitor that exhibits broad spectrum antitumor activity in vitro and in vivo
Christian A Hassig
Kalypsys, Inc, 10420 Wateridge Circle, San Diego, CA 92121, USA
Mol Cancer Ther 7:1054-65. 2008
..The biological and pharmaceutical profile of KD5170 supports its continued preclinical and clinical development as a broad spectrum anticancer agent...
