Research Topics
| Naj A SharifSummaryAffiliation: Alcon Research Country: USA Publications
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Detail Information
Publications
3-Oxa-15-cyclohexyl prostaglandin DP receptor agonists as topical antiglaucoma agentsMark R Hellberg
Department of Medicinal Chemistry, Alcon Research, Ltd, Pharmaceutical Products Research, 6201 South Freeway, Fort Worth, TX 76134, USA
Bioorg Med Chem 10:2031-49. 2002..In this manner, 136 g of AL-6598 was synthesized under GMP conditions for evaluation in phase I clinical trials...
Serotonin-2 receptor agonists as novel ocular hypotensive agents and their cellular and molecular mechanisms of actionNajam A Sharif
Pharmaceutical Products Research, Alcon Research Ltd, 6201 South Freeway, Fort Worth, TX 76248, USA
Curr Drug Targets 11:978-93. 2010..Thus, functional 5HT(2A) receptors are present in human ocular cells involved in IOP reduction and this correlates with the ability of 5HT(2A) agonists to lower IOP in Cynomolgus monkeys, a surrogate for human subjects...
Ocular hypotensive FP prostaglandin (PG) analogs: PG receptor subtype binding affinities and selectivities, and agonist potencies at FP and other PG receptors in cultured cellsN A Sharif
Molecular Pharmacology Unit, Alcon Research, Ltd, Fort Worth, TX 76134 2099, USA
J Ocul Pharmacol Ther 19:501-15. 2003....
Pharmacological characterization and identification of EP3 prostanoid receptor binding sites in hamster uterus homogenatesN A Sharif
Molecular Pharmacology Unit, Alcon Research Ltd, South Freeway, Fort Worth, TX 76134 2099, USA
J Pharm Pharmacol 56:197-203. 2004..002), vs cloned rat EP(3) receptor (r = 0.9, P < 0.0004), and vs EP(3) receptor-mediated functional responses (r = 0.72, P < 0.02) substantiated the conclusion that the hamster uterus contains EP(3) receptor binding sites...
Binding affinities of ocular hypotensive beta-blockers levobetaxolol, levobunolol, and timolol at endogenous guinea pig beta-adrenoceptorsN A Sharif
Molecular Pharmacology, Alcon Research, Ltd, Fort Worth, TX 76134, USA
J Ocul Pharmacol Ther 20:93-9. 2004..These data indicated that while levobetaxolol and betaxolol possessed a 193-233-fold selectivity for beta(1)-receptors, levobunolol exhibited a 140-fold beta(2)-receptor selectivity and (l)-timolol was essentially nonselective...
Cloned human 5-HT1A receptor pharmacology determined using agonist binding and measurement of cAMP accumulationNajam A Sharif
Molecular Pharmacology Unit, Pharmaceutical Products Research, Alcon Research, Ltd, Fort Worth, TX 76134 2099, USA
J Pharm Pharmacol 56:1267-74. 2004..58, P <0.05). The present study provides a detailed pharmacological characterization of the ch-5-HT1A receptor using binding and functional assays...
Molecular pharmacology of the DP/EP2 class prostaglandin AL-6598 and quantitative autoradiographic visualization of DP and EP2 receptor sites in human eyesNaj A Sharif
Molecular Pharmacology Unit, Alcon Research, Ltd, Fort Worth, TX 76134 2099, USA
J Ocul Pharmacol Ther 20:489-508. 2004..The IOP-lowering activities of these compounds may involve both the inflow and outflow mechanisms, as DP and EP2 receptors were visualized in human ocular tissues involved in such aqueous humor dynamics...
Ocular hypotensive DP-class prostaglandin receptor affinities determined by quantitative autoradiography on human eye sectionsNajam A Sharif
Molecular Pharmacology Unit, Alcon Research, Ltd, Fort Worth, TX 76134 2099, USA
J Ocul Pharmacol Ther 21:121-32. 2005..The pharmacological attributes of [3H]BWA868C-labeled receptor sites studied using in situ quantitative autoradiography matched those previously documented for several other DP-receptor-containing cells and tissues...
Serotonin receptor subtype mRNA expression in human ocular tissues, determined by RT-PCRNajam A Sharif
Ophthalmology Discovery Research, Alcon Research, Ltd, Fort Worth, TX 76134, USA
Mol Vis 12:1040-7. 2006..To determine the relative density and tissue localization of mRNAs for serotonin (5-hydroxytryptamine; 5HT) receptor subtypes in human ocular tissues and correlate with their possible functions in the eye...
Preclinical pharmacology of AL-12182, a new ocular hypotensive 11-oxa prostaglandin analogNajam A Sharif
Ophthalmology Discovery Research, Alcon Research, Ltd, Fort Worth, TX 76137, USA
J Ocul Pharmacol Ther 22:291-309. 2006....
Serotonin-2 (5-HT2) receptor-mediated signal transduction in human ciliary muscle cells: role in ocular hypotensionNajam A Sharif
Ophthalmology Discovery Research, Alcon Research, Ltd, Fort Worth, TX 76134 2099, USA
J Ocul Pharmacol Ther 22:389-401. 2006....
AL-34662: a potent, selective, and efficacious ocular hypotensive serotonin-2 receptor agonistNajam A Sharif
Ophthalmology Discovery Research, Alcon Research, Ltd, Fort Worth, TX 76134, USA
J Ocul Pharmacol Ther 23:1-13. 2007..A variety of well-documented in vitro and in vivo procedures were utilized to study the pharmacological attributes of AL-34662...
Intracellular signaling in human iridial fibroblasts and iridial melanocytes in response to prostaglandins, endothelin, isoproterenol, and other pharmacological agentsNajam A Sharif
Pharmaceutical Research, Alcon Research, Ltd, Fort Worth, Texas 76134, USA
Curr Eye Res 36:310-20. 2011....
Cat iris sphincter smooth-muscle contraction: comparison of FP-class prostaglandin analog agonist activitiesNajam A Sharif
Ophthalmology Discovery Research, Alcon Research Ltd, Fort Worth, TX 76134, USA
J Ocul Pharmacol Ther 24:152-63. 2008..84). These data confirm the presence of functional FP-receptors in the cat iris sphincter, which are exquisitely well coupled and which respond to a variety of FP-class PG analogs with differing potencies...
Synthetic FP-prostaglandin-induced contraction of rat uterus smooth muscle in vitroNajam A Sharif
Alcon Research, Ltd, Fort Worth, TX 76134 2099, USA
Prostaglandins Leukot Essent Fatty Acids 78:199-207. 2008....
Cabergoline: Pharmacology, ocular hypotensive studies in multiple species, and aqueous humor dynamic modulation in the Cynomolgus monkey eyesNajam A Sharif
Discovery Ophthalmology Research, Alcon Research Ltd, Fort Worth, TX, USA
Exp Eye Res 88:386-97. 2009....
Human conjunctival epithelial cell responses to platelet-activating factor (PAF): signal transduction and release of proinflammatory cytokinesNajam A Sharif
Pharmaceutical Products Research, Core Pharmacology and Imaging, Alcon Research Ltd, Fort Worth, TX 76134, USA
Mol Vis 15:1153-61. 2009....
Platelet-activating factor-induced intracellular signaling and release of cytokines and prostaglandin E2 in immortalized human corneal epithelial cellsNajam A Sharif
Pharmaceutical Products Research, Alcon Research, Ltd, Fort Worth, Texas 76134, USA
J Ocul Pharmacol Ther 26:21-9. 2010....
Human trabecular meshwork cells express functional serotonin-2A (5HT2A) receptors: role in IOP reductionNajam A Sharif
Ophthalmology Discovery Research, Alcon Research, Ltd, Fort Worth, Texas 76134, USA
Invest Ophthalmol Vis Sci 47:4001-10. 2006..To correlate in vitro findings with intraocular pressure (IOP) changes in conscious ocular hypertensive cynomolgus monkeys...
Cloned human EP1 prostanoid receptor pharmacology characterized using radioligand binding techniquesNajam A Sharif
Molecular Pharmacology Unit, Alcon Research, Ltd, Fort Worth, Texas 76134, USA
J Pharm Pharmacol 54:539-47. 2002..g. ZK118182 (K = 73.4 +/- 8.6 nM) and ZK110841 (K = 166 +/- 20 nM)). All FP (e.g. travoprost acid, fluprostenol), IP (iloprost) and TP (SQ29548) receptor-specific ligands exhibited low affinity (Ki > or = 1 microM)...
Pharmacological and molecular biological (RT-PCR) characterization of functional TP prostanoid receptors in immortalized human non-pigmented ciliary epithelial cellsN A Sharif
Molecular Pharmacology Unit, Alcon Research Ltd, Fort Worth, Texas 76134 2099, USA
J Ocul Pharmacol Ther 18:141-62. 2002..The TPalpha receptors on NPE cells may be responsible for inhibiting aqueous humor production and may help explain the intraocular pressure-lowering effects of certain TP agonists...
Agonist activity of bimatoprost, travoprost, latanoprost, unoprostone isopropyl ester and other prostaglandin analogs at the cloned human ciliary body FP prostaglandin receptorN A Sharif
Molecular Pharmacology Unit, Alcon Research, Ltd, Fort Worth, Texas 76134 2099, USA
J Ocul Pharmacol Ther 18:313-24. 2002..0 - 2.1 microM; n = 3). These studies have demonstrated, for the first time, agonist activities of the currently known and marketed ocular hypotensive prostaglandin analogs at the cloned human ciliary body FP prostaglandin receptor...
Bimatoprost and its free acid are prostaglandin FP receptor agonistsN A Sharif
Molecular Pharmacology Unit, Alcon Research, Ltd, 6201 South Freeway, Fort Worth, TX 76134, USA
Eur J Pharmacol 432:211-3. 2001..Furthermore, AL-8810 ((5Z, 13E)-(9S,11S,15R)-9,15-dihydroxy-11-fluoro-15-(2-indanyl)-16,17,18,19,20-pentanor-5,13-prostadienoic acid), an FP receptor antagonist, blocked the bimatoprost-induced [Ca(2+)](i) mobilization...
Levobetaxolol (Betaxon) and other beta-adrenergic antagonists: preclinical pharmacology, IOP-lowering activity and sites of action in human eyesN A Sharif
Molecular Pharmacology Unit, Pharmaceutical Products Research, Alcon Research, Ltd, Fort Worth, TX 76134 2099, USA
J Ocul Pharmacol Ther 17:305-17. 2001..In conclusion, levobetaxolol is a potent, high affinity and beta1-selective IOP-lowering beta-adrenoceptor antagonist...
AL-3138 antagonizes FP prostanoid receptor-mediated inositol phosphates generation: comparison with some purported FP antagonistsN A Sharif
Molecular Pharmacology Unit, Alcon Research Ltd, Fort Worth, TX 76134, USA
J Pharm Pharmacol 52:1529-39. 2000....
Bimatoprost (Lumigan((R))) is an agonist at the cloned human ocular FP prostaglandin receptor: real-time FLIPR-based intracellular Ca(2+) mobilization studiesN A Sharif
Molecular Pharmacology Unit R2 19, Alcon Research Limited, 6201 South Freeway, 76134, Fort Worth, TX, USA
Prostaglandins Leukot Essent Fatty Acids 68:27-33. 2003..Therefore, the prodrug bimatoprost and its hydrolytic product, bimatoprost free acid, bind to and activate the human ocular FP prostaglandin receptor to mobilize [Ca(2+)](i), thus behaving as FP receptor agonists...
Affinities, selectivities, potencies, and intrinsic activities of natural and synthetic prostanoids using endogenous receptors: focus on DP class prostanoidsN A Sharif
Molecular Pharmacology Unit, Alcon Research, Ltd, Fort Worth, Texas 76134 2099, USA
J Pharmacol Exp Ther 293:321-8. 2000..9-8.2, n = 5-9). The pharmacological properties of some natural and numerous DP class synthetic prostanoids have been determined using endogenous receptors...
Pharmacology and autoradiography of human DP prostanoid receptors using [(3)H]-BWA868C, a DP receptor-selective antagonist radioligandN A Sharif
Molecular Pharmacology Unit, Alcon Research Ltd, 6201 South Freeway, Fort Worth, Texas, TX 76134, USA
Br J Pharmacol 131:1025-38. 2000..3)H]-BWA868C may prove useful for future homogenate-based and autoradiographic studies on the DP receptor...
Identification and characterization of the ocular hypotensive efficacy of travoprost, a potent and selective FP prostaglandin receptor agonist, and AL-6598, a DP prostaglandin receptor agonistMark R Hellberg
Department of Medicinal Chemistry, Alcon Research Ltd, 6201 South Freeway, Fort Worth, TX 76134, USA
Surv Ophthalmol 47:S13-33. 2002..The acute and, apparently, conjunctival hyperemia associated with topical ocular AL-6598 can be attenuated while maintaining intraocular pressure-lowering efficacy by formulating with brimonidine...
Human ciliary muscle cell responses to FP-class prostaglandin analogs: phosphoinositide hydrolysis, intracellular Ca2+ mobilization and MAP kinase activationNaj A Sharif
Molecular Pharmacology Unit, Alcon Research, Ltd, Fort Worth, TX 76134 2099, USA
J Ocul Pharmacol Ther 19:437-55. 2003....
Human trabecular meshwork cell responses induced by bimatoprost, travoprost, unoprostone, and other FP prostaglandin receptor agonist analoguesNajam A Sharif
Molecular Pharmacology Unit, Glaucoma Research, Alcon Research, Ltd, Fort Worth, Texas, USA
Invest Ophthalmol Vis Sci 44:715-21. 2003..Bimatoprost, travoprost, latanoprost, unoprostone isopropyl ester, and their respective free acids were shown to be FP agonists in the h-TM cells...
Pharmacological characterization of a serotonin receptor (5-HT7) stimulating cAMP production in human corneal epithelial cellsJulie Y Crider
Molecular Pharmacology Unit, Alcon Research, Ltd, Fort Worth, Texas 76134-2099, USA
Invest Ophthalmol Vis Sci 44:4837-44. 2003....
Aqueous humor concentrations of bimatoprost free acid, bimatoprost and travoprost free acid in cataract surgical patients administered multiple topical ocular doses of LUMIGAN or TRAVATANRobert Faulkner
Alcon Research, Ltd, Fort Worth, TX 76134, USA
J Ocul Pharmacol Ther 26:147-56. 2010....
AL-12182, a novel 11-oxa prostaglandin analog with topical ocular hypotensive activity in the monkeyRobert D Selliah
Alcon Research, Ltd, Pharmaceutical Products Research, 6201 South Freeway, MS R2-39 Fort Worth, TX 76134, USA
Bioorg Med Chem Lett 14:4525-8. 2004..AL-12182 was synthesized on multigram scale starting with D-sorbitol...
Pharmacological properties and discriminative stimulus effects of a novel and selective 5-HT2 receptor agonist AL-38022A [(S)-2-(8,9-dihydro-7H-pyrano[2,3-g]indazol-1-yl)-1-methylethylamine]Jesse A May
Ophthalmology Discovery Research, Alcon Research, Ltd, 6201 South Freeway, Fort Worth, Texas 76134, United States
Pharmacol Biochem Behav 91:307-14. 2009..The pharmacological profile of AL-38022A suggests that it could be a useful tool in defining 5-HT2 receptor signaling and receptor characterization where 5-HT may function as a neurotransmitter...
Discovery of 13-oxa prostaglandin analogs as antiglaucoma agents: synthesis and biological activityZixia Feng
Medicinal Chemistry, Ophthalmic Products Research, Alcon Research Ltd, 6201 South Freeway, Mail code R2 39, Fort Worth, TX 76134, USA
Bioorg Med Chem 17:576-84. 2009..8 microg). AL-16049 also produced no signs of ocular irritation or discomfort in the cat at the doses evaluated...
Adenylyl cyclase activity mediated by beta-adrenoceptors in immortalized human trabecular meshwork and non-pigmented ciliary epithelial cellsJulie Y Crider
Molecular Pharmacology Unit, Alcon Research, Ltd, Fort Worth, Texas 76134 2099, USA
J Ocul Pharmacol Ther 18:221-30. 2002..These detailed pharmacological studies using a variety of agonists and antagonists further supported the presence of beta2-adrenergic receptors in immortalized human NPE and TM cells...
A novel and selective 5-HT2 receptor agonist with ocular hypotensive activity: (S)-(+)-1-(2-aminopropyl)-8,9-dihydropyrano[3,2-e]indoleJesse A May
Medicinal Chemistry Department, Ophthalmic Products Research, Alcon Research, Ltd, 6201 South Freeway, Fort Worth, Texas 76134, USA
J Med Chem 46:4188-95. 2003..1 mmHg, -37%). Thus, 11 is a potent full agonist with selectivity for the 5-HT2 receptor and is anticipated to serve as a useful tool in exploring the role of the 5-HT2 receptor and its effector system in controlling intraocular pressure...
Evaluation of the ocular hypotensive response of serotonin 5-HT1A and 5-HT2 receptor ligands in conscious ocular hypertensive cynomolgus monkeysJesse A May
Ophthalmic Products Research, Alcon Research, Ltd, 6201 South Freeway, Ft Worth, TX 76134, USA
J Pharmacol Exp Ther 306:301-9. 2003....
Real-time intracellular Ca2+ mobilization by travoprost acid, bimatoprost, unoprostone, and other analogs via endogenous mouse, rat, and cloned human FP prostaglandin receptorsCurtis R Kelly
Molecular Pharmacology Unit, Pharmaceutical Products Research, Alcon Research, Ltd, Fort Worth, Texas 76134, USA
J Pharmacol Exp Ther 304:238-45. 2003....
1-((S)-2-aminopropyl)-1H-indazol-6-ol: a potent peripherally acting 5-HT2 receptor agonist with ocular hypotensive activityJesse A May
Ophthalmology Discovery Research, Alcon Research, Ltd, 6201 South Freeway, Fort Worth, Texas 76134, USA
J Med Chem 49:318-28. 2006..Compound 9 appears to be an excellent 5-HT(2) receptor agonist for conducting further studies directed toward a clinical proof-of-concept study for this class of ocular hypotensive agents...
Pharmacological evidence for a functional serotonin-2B receptor in a human uterine smooth muscle cell lineCurtis R Kelly
Molecular Pharmacology R2 43, Alcon Research, Ltd, 6201 South Freeway, Fort Worth, TX 76134, USA
J Pharmacol Exp Ther 317:1254-61. 2006..4 nM) in the HUSMC PI turnover assays. Taken together, these studies strongly suggest the presence of a functionally active 5-HT2B receptor subtype in HUSMCs. The physiological role of this receptor in these cells remains to be defined...
Novel benzodifuran analogs as potent 5-HT2A receptor agonists with ocular hypotensive activityZixia Feng
Alcon Research, Ltd, Research Chemistry, 6201 South Freeway, Fort Worth, TX 76134, USA
Bioorg Med Chem Lett 17:2998-3002. 2007..Topical ocular administration of 5, 18, and 25 effectively reduced intra-ocular pressure in the hypertensive cynomolgus monkey eye in the range of 25-37%...
Changes in ocular aquaporin expression following optic nerve crushAdnan Dibas
Department of Pharmacology and Neuroscience, University of North Texas Health Science Center at Fort Worth, Fort Worth, TX, USA
Mol Vis 16:330-40. 2010..This study was designed to analyze changes in the expression of AQP4 (water selective channel) and AQP9 (water and lactate channel) following ONC in the rat...
NPR-B natriuretic peptide receptors in human corneal epithelium: mRNA, immunohistochemistochemical, protein, and biochemical pharmacology studiesParvaneh Katoli
Pharmaceutical Research, Alcon Research, Ltd, Fort Worth, TX 76134, USA
Mol Vis 16:1241-52. 2010....
Pharmacology of serotonin receptors modulating electrically-induced [3h]-norepinephrine release from isolated mammalian iris-ciliary bodiesLydia C Harris
Department of Pharmacy Sciences, School of Pharmacy and Allied Health Professions, Creighton University, Omaha, NE 68178, USA
J Ocul Pharmacol Ther 18:339-48. 2002..We conclude that the excitatory prejunctional 5-HT heteroreceptors present in bovine iris-ciliary bodies belong to the 5-HT3 receptor subtype...
Beta-oxygenated analogues of the 5-HT2A serotonin receptor agonist 1-(4-bromo-2,5-dimethoxyphenyl)-2-aminopropaneRichard A Glennon
Department of Medicinal Chemistry, Box 980540, School of Pharmacy, Virginia Commonwealth University, Richmond, Virginia 23298, USA
J Med Chem 47:6034-41. 2004..e., topical), and concentrations necessary to reduce intraocular pressure, compounds such as 6d should demonstrate minimal central effects at potentially useful therapeutic doses and offer useful leads for further development...
Glucose-deprivation-induced [3H]D-aspartate release from isolated bovine and human retinaeSunny E Ohia
Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX 77204, USA
J Ocul Pharmacol Ther 19:599-609. 2003..This process appears to be receptor-mediated and dependent on extracellular Ca2+ and is similar to previous reports pertaining to brain tissues...
