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Publications

LX4211

B Zambrowicz, J Freiman, P M Brown, K S Frazier, A Turnage, J Bronner, D Ruff, M Shadoan, P Banks, F Mseeh, D B Rawlins, N C Goodwin, R Mabon, B A Harrison, A Wilson, A Sands, D R Powell. LX4211, a Dual SGLT1/SGLT2 Inhibitor, Improved Glycemic Control in Patients With Type 2 Diabetes in a Randomized, Placebo-Controlled Trial. Clinical Pharmacology & Therapeutics (2012); advance online publication 27 June 2012.

N.C. Goodwin, R. Mabon, B.A. Harrison, M.K. Shadoan, Z.Y. Almstead, Y. Xie, J. Healy, L.M. Buhring, C.M. DaCosta, J. Bardenhagen, F. Mseeh, Q. Liu, A. Nouraldeen, A.G.E. Wilson, S.D. Kimball, D.R. Powell, and D.B. Rawlins, Novel l-Xylose Derivatives as Selective Sodium-Dependent Glucose Cotransporter 2 (SGLT2) Inhibitors for the Treatment of Type 2 Diabetes. Journal of Medicinal Chemistry, 2009. 52(20): p. 6201-6204.

Telotristat etiprate (LX1032)

C. Pappas, A. Turnage, K.S. Frazier, Q. Liu, and P. Brown, LX1032: A potential new therapy for carcinoid syndrome (CS). J Clin Oncol (Meeting Abstracts), 2009. 27(15S): p. e14555-.

Zuetenhorst JM, Taal BG.  Metastatic carcinoid tumors: a clinical review. Oncologist, 2005. 10(2):123-131.

Alfieri AB, L.X. Cubeddu. Treatment with Para-chlorophenylalanine Antagonises the Emetic Response and the Serotonin-releasing Actions of Cisplatin in Cancer Patients. British Journal of Cancer, 1995. 71(3):629-632

Engelman K, Lovenberg W and Sjoerdsma A. Inhibition of Serotonin Synthesis by Para-chlorophenylalanine in Patients with the Carcinoid Syndrome. New England Journal of Medicine, 1967. 277(21):1103-1108.

LX1033/LX1031

P. Brown, D.A. Drossman, A. Wood, G. Cline, K. Frazier, J. Jackson, J. Bronner, J. Freiman, B. Zambrowicz, A. Sands, M. Gershon, The Tryptophan Hydroxylase Inhibitor LX1031 Shows Clinical Benefit in Patients with Nonconstipating Irritable Bowel Syndrome, Gastroenterology, 2011. 

Gershon MD and Tack J. The serotonin signaling system: from basic understanding to drug development for functional GI disorders. Gastroenterology, 2007 132:397-414. 

Gershon MD. Nerves, reflexes, and the enteric nervous system: pathogenesis of the irritable bowel syndrome. J Clin Gastroenterol 2005. 39:S184-193.

De Ponti F. Pharmacology of serotonin: what a clinician should know. Gut 2004. 53:1520-1535.

Gershon MD. Serotonin and its implication for the management of irritable bowel syndrome. Rev Gastroenterol Disord 3 Suppl 2003. 2:S25-34.

Gingrich JA, Ansorge MS, Merker R, Weisstaub N and Zhou M. New lessons from knockout mice: The role of serotonin during development and its possible contribution to the origins of neuropsychiatric disorders. CNS Spectr 2003. 8(8);572-7.

Veenstra-VanderWeele J., Cook EH. Knockout Mouse Points to Second Form of Tryptophan Hydroxylase. Mol Interv 2003. 3(2):72-5, 50.

Walther DJ, Peter JU, Bashammakh S, Hortnagl H, Voits M, Fink H and Bader M. Synthesis of serotonin by a second tryptophan hydroxylase isoform. Science 2003. 299:76.

LX2931

Bagdanoff JT, Donoviel MS, Nouraldeen A, Carlsen M, Jessop TC, Tarver J, Aleem S, Dong L, Zhang H, Boteju L, Hazelwood J, Yan J, Bednarz M, Layek S, Owusu IB, Gopinathan S, Moran L, Lai Kramer J, Kimball SD, Yalamanchili P, Heydorn WE, Frazier KS, Brooks B, Brown P, Wilson A, Sonnenburg WK, Main A, Carson KG, Oravecz T, Augeri DJ. Inhibition of sphingosine 1-phosphate lyase for the treatment of rheumatoid arthritis: discovery of (E)-1-(4-((1R, 2S, 3R)-1,2,3,4-tetrahydroxybutyl)-1H-imidazol-2-yl)ethanone oxime (LX2931) and 1R, 2S, 3R)-1-(2-(isoxazol-3-yl)-lH-imidazol-4-yl)butane-1,2,3,4-tetraol (LX 2932). J Med Chem, 2010.

J.T. Bagdanoff, M.S. Donoviel, A. Nouraldeen, J. Tarver, Q. Fu, M. Carlsen, T.C. Jessop, H. Zhang, J. Hazelwood, H. Nguyen, S.D.P. Baugh, M. Gardyan, K.M. Terranova, J. Barbosa, J. Yan, M. Bednarz, S. Layek, L.F. Courtney, J. Taylor, A.M. Digeorge-Foushee, S. Gopinathan, D. Bruce, T. Smith, L. Moran, E. O'Neill, J. Kramer, Z. Lai, S.D. Kimball, Q. Liu, W. Sun, S. Yu, J. Swaffield, A. Wilson, A. Main, K.G. Carson, T. Oravecz, and D.J. Augeri, Inhibition of Sphingosine-1-Phosphate Lyase for the Treatment of Autoimmune Disorders. Journal of Medicinal Chemistry, 2009. 52(13): p. 3941-3953.

P. Vogel, M.S. Donoviel, R. Read, G.M. Hansen, J. Hazlewood, S.J. Anderson, W. Sun, J. Swaffield, and T. Oravecz, Incomplete inhibition of sphingosine 1-phosphate lyase modulates immune system function yet prevents early lethality and non-lymphoid lesions. PLoS ONE, 2009. 4(1): p. e4112.
 

Other Research Publications

Paes KT, Wang E, Henze K, Vogel P, Read R, Suwanichkul A, Kirkpatrick LL, Potter D, Newhouse MM, Rice DS.  Frizzled 4 is required for retinal angiogenesis and maintenance of the blood-retina barrier.  Invest Ophthalmol Vis Sci., 2011. 

Stadanlick JE, Zhang Z, Lee S, Hemann M, Biery M, Carleton MO, Zambetti GP, Anderson SJ, Oravecz T, Wiest DL.  Developmental Arrest of T Cells in Rpl22-Deficient Mice Is Dependent upon Multiple p53 Effectors.  The Journal of Immunology, 2011. 

Vogel P, Read R, Hansen G, Wingert J, Dacosta CM, Buhring LM, Shadoan M.  Pathology of congenital generalized lipodystrophy in agpat 2-/- mice.  Vet Pathol, 2011. 

Read R, Savelieva K, Baker K, Hansen G, Vogel P.  Histopahtological and neurological features of Atg4b knockout mice.  Vet Pathol, 2011. 

Revelli JP, Smith D, Allen J, Jeter-Jones S, Shadoan MK, Desai U, Scheider M, van Sligtenhorst I, Kirkpatrick L, Platt KA, Suwanichkul A, Savelieva K, Gerhardt B, Mitchell J, Syrewicz J, Zambrowicz B, Hamman BD, Vogel P, Powell DR. Profound obesity secondary to hyperphagia in mice lacking kinase suppressor of ras 2.  Obesity, 2011. 

Harris DP, Vogel P, Wims M, Moberg K, Humphries J, Jhaver KG, DaCosta CM, Shadoan MK, Xu N, Hansen GM, Balakrishnan S, Domin J, Powell DR, Oravecz T. Requirement for class II phophoinositide 3-kinase C2alpha in maintenance of glomerular structure and function. Mol Cell Biol, 2011.

Salojin KV, Cabrera RM, Sun W, Chang WC, Lin C, Duncan L, Platt KA, Read R, Vogel P, Liu Q, Finnell RH, Oravecz T.  A mouse model of hereditary folate malabsorption: deletion of the PCFT gene leads to systemic folate deficiency. Blood, 2011. 

Conover CA, Boldt HB, Bale LK, Clifton KB, Grell JA, Mader JR, Mason EH, Powell DR.  Pregnancy-Associated Plasma Protein-A2 (PAPP-A2): Tissue Expression and Biological Consequences of Gene Knockout in Mice. Endocrinology, 2011.

Cianchetta G, Stouch T, Yu W, Shi ZC, Tari LW, Swanson RV, Hunter MJ, Hoffman ID, Liu Q. Mechanism of Inhibition of Novel Tryptophan Hydroxylase Inhibitors Revealed by Co-Cyrstal Structures and Kinetic Analysis.  Current Chemical Genomics, 2010. 

Al-Shami A, Jhaver KG, Vogel P, Wilkins C, Humphries J, Davis JJ, Xu N, Potter DG, Gerhardt B, Mullinax R, Shirley CR, Anderson SJ, Oravecz T. Regulators of the Proteasome Pathway, Uch37 and Rpn 13, Play Distinct Roles in Mouse Development. PLoS One, 2010. 

P. Vogel, G. Hansen, G. Fontenot, and R. Read, Tubulin Tyrosine Ligase–Like 1 Deficiency Results in Chronic Rhinosinusitis and Abnormal Development of Spermatid Flagella in Mice. Vet Pathol, 2010.

A. Wilson, A. Nouraldeen, and S. Gopinathan, A new paradigm for improving oral absorption of drugs in discovery: role of physiochemical properties, different excipients and the pharmaceutical scientist. Future Medicinal Chemistry, 2010. 2(1): p. 1-5.

W. Zhang, K.V. Savelieva, A. Suwanichkul, D.L. Small, L. Kirkpatrick, N. Xu, T.H. Lanthorn, and G.L. Ye, Transmembrane and Ubiquitin-Like Domain Containing 1 (Tmub1) Regulates Locomotor Activity and Wakefulness in Mice and Interacts with CAMLG. PLoS One, 2010. 5(6): p. 1-10.

A. Al-Shami, C. Wilkins, J. Crisostomo, D. Seshasayee, F. Martin, N. Xu, A. Suwanichkul, S.J. Anderson, and T. Oravecz, The Adaptor Protein Sh2d3c Is Critical for Marginal Zone B Cell Development and Function. J Immunol, 2010.

I. Rajan, R. Read, D.L. Small, J. Perrard, and P. Vogel, An Alternative Splicing Variant in Clcn7-/- Mice Prevents Osteopetrosis but Not Neural and Retinal Degeneration. Vet Pathol, 2010.

X.Q. Yu, J. Kramer, L. Moran, E. O'Neill, A. Nouraldeen, T. Oravecz, and A.G. Wilson, Pharmacokinetic/pharmacodynamic modelling of 2-acetyl-4(5)-tetrahydroxybutyl imidazole-induced peripheral lymphocyte sequestration through increasing lymphoid sphingosine 1-phosphate. Xenobiotica, 2010. 40(5): p. 350-6.

K.H. Gabbay, K.M. Bohren, R. Morello, T. Bertin, J. Liu, and P. Vogel, Ascorbate Synthesis Pathway: Dual Role of Ascorbate in Bone Homeostasis. Biological Chemistry, 2010. 285(25): p. 19510-20.

X.C. Yu, M. Miranda, Z. Liu, S. Patel, N. Nguyen, K. Carson, Q. Liu, and J.C. Swaffield, Novel potent inhibitors of deoxycytidine kinase identified and compared by multiple assays. J Biomol Screen, 2010. 15(1): p. 72-9.

P. Vogel, R. Read, G.M. Hansen, L.C. Freay, B.P. Zambrowicz, and A.T. Sands, Situs inversus in Dpcd/Poll-/-, Nme7-/- , and Pkd1l1-/- mice. Vet Pathol, 2010. 47(1): p. 120-31.

S. Limura and W. Wu, Palladium-catalyzed borylation of L-tyrosine triflate derivative with pinacolborane: practical route to 4-borono-L-phenylalanine (L-BPA) derivatives. Tetrahedron Letters, 2010. 51(10): p. 1353-55.

K.B. Baker, S.P. Wray, R. Ritter, S. Mason, T.H. Lanthorn, and K.V. Savelieva, Male and female Fmr1 knockout mice on C57 albino background exhibit spatial learning and memory impairments. Genes Brain Behav, 2010.

J.A. Kramer, E. O'Neill, M.E. Phillips, D. Bruce, T. Smith, M.M. Albright, S. Bellum, S. Gopinathan, W.E. Heydorn, X. Liu, A. Nouraldeen, B.J. Payne, R. Read, P. Vogel, X.Q. Yu, and A.G. Wilson, Early toxicology signal generation in the mouse. Toxicol Pathol, 2010. 38(3): p. 452-71.

A. Wilson and X.Q. Yu, The role of pharmacokinetic and pharmacokinetic/pharmacodynamic modeling in drug discovery and development. Future Med. Chem., 2010. 2(6): p. 923-928.

J.E. Tarver, T.C. Jessop, M. Carlsen, D.J. Augeri, Q. Fu, J.P. Healy, A. Heim-Riether, A. Xu, J.A. Taylor, M. Shen, P.E. Keyes, S. David Kimball, X.C. Yu, M. Miranda, Q. Liu, J.C. Swaffield, A. Nouraldeen, A.G. Wilson, R. Finch, K. Jhaver, A.M. Foushee, S. Anderson, T. Oravecz, and K.G. Carson, 5-Fluorocytosine derivatives as inhibitors of deoxycytidine kinase. Bioorg Med Chem Lett, 2009.

T.C. Jessop, J.E. Tarver, M. Carlsen, A. Xu, J.P. Healy, A. Heim-Riether, Q. Fu, J.A. Taylor, D.J. Augeri, M. Shen, T.R. Stouch, R.V. Swanson, L.W. Tari, M. Hunter, I. Hoffman, P.E. Keyes, X.C. Yu, M. Miranda, Q. Liu, J.C. Swaffield, S. David Kimball, A. Nouraldeen, A.G. Wilson, A.M. Foushee, K. Jhaver, R. Finch, S. Anderson, T. Oravecz, and K.G. Carson, Lead optimization and structure-based design of potent and bioavailable deoxycytidine kinase inhibitors. Bioorg Med Chem Lett, 2009.

H. Jin, G. Cianchetta, A. Devasagayaraj, K. Gu, B. Marinelli, L. Samala, S. Scott, T. Stouch, A. Tunoori, Y. Wang, Y. Zang, C. Zhang, S. David Kimball, A.J. Main, Z.M. Ding, W. Sun, Q. Yang, X.Q. Yu, D.R. Powell, A. Wilson, Q. Liu, and Z.C. Shi, Substituted 3-(4-(1,3,5-triazin-2-yl)-phenyl)-2-aminopropanoic acids as novel tryptophan hydroxylase inhibitors. Bioorg Med Chem Lett, 2009. 19(17): p. 5229-32.

M. Boonen, P. Vogel, K.A. Platt, N. Dahms, and S. Kornfeld, Mice Lacking Mannose 6-Phosphate Uncovering Enzyme Activity Have a Milder Phenotype than Mice Deficient for N-Acetylglucosamine-1-Phosphotransferase Activity. Mol. Biol. Cell, 2009. 20(20): p. 4381-4389.

L.A. Hu, T. Zhou, J. Ahn, S. Wang, J. Zhou, Y. Hu, and Q. Liu, Human and mouse trace amine-associated receptor 1 have distinct pharmacology towards endogenous monoamines and imidazoline receptor ligands. Biochem J, 2009. 424(1): p. 39-45.

E.C. Lee, U. Desai, G. Gololobov, S. Hong, X. Feng, X.C. Yu, J. Gay, N. Wilganowski, C. Gao, L.L. Du, J. Chen, Y. Hu, S. Zhao, L. Kirkpatrick, M. Schneider, B.P. Zambrowicz, G. Landes, D.R. Powell, and W.K. Sonnenburg, Identification of a new functional domain in angiopoietin-like 3 (ANGPTL3) and angiopoietin-like 4 (ANGPTL4) involved in binding and inhibition of lipoprotein lipase (LPL). J Biol Chem, 2009. 284(20): p. 13735-45.

B.A. Harrison, N.A. Whitlock, M.V. Voronkov, Z.Y. Almstead, K.-j. Gu, R. Mabon, M. Gardyan, B.D. Hamman, J. Allen, S. Gopinathan, B. McKnight, M. Crist, Y. Zhang, Y. Liu, L.F. Courtney, B. Key, J. Zhou, N. Patel, P.W. Yates, Q. Liu, A.G.E. Wilson, S.D. Kimball, C.E. Crosson, D.S. Rice, and D.B. Rawlins, Novel Class of LIM-Kinase 2 Inhibitors for the Treatment of Ocular Hypertension and Associated Glaucoma. Journal of Medicinal Chemistry, 2009.

K.V. Savelieva, S. Zhao, V.M. Pogorelov, I. Rajan, Q. Yang, E. Cullinan, and T.H. Lanthorn, Genetic disruption of both tryptophan hydroxylase genes dramatically reduces serotonin and affects behavior in models sensitive to antidepressants. PLoS ONE, 2008. 3(10): p. e3301.

G.M. Hansen, D.C. Markesich, M.B. Burnett, Q. Zhu, K.M. Dionne, L.J. Richter, R.H. Finnell, A.T. Sands, B.P. Zambrowicz, and A. Abuin, Large-scale gene trapping in C57BL/6N mouse embryonic stem cells. Genome Res, 2008. 18(10): p. 1670-9.

R. Brommage, U. Desai, J.P. Revelli, D.B. Donoviel, G.K. Fontenot, C.M. Dacosta, D.D. Smith, L.L. Kirkpatrick, K.J. Coker, M.S. Donoviel, D.E. Eberhart, K.H. Holt, M.R. Kelly, W.J. Paradee, A.V. Philips, K.A. Platt, A. Suwanichkul, G.M. Hansen, A.T. Sands, B.P. Zambrowicz, and D.R. Powell, High-throughput screening of mouse knockout lines identifies true lean and obese phenotypes. Obesity (Silver Spring), 2008. 16(10): p. 2362-7.

Z.C. Shi, A. Devasagayaraj, K. Gu, H. Jin, B. Marinelli, L. Samala, S. Scott, T. Stouch, A. Tunoori, Y. Wang, Y. Zang, C. Zhang, S.D. Kimball, A.J. Main, W. Sun, Q. Yang, A. Nouraldeen, X.Q. Yu, E. Buxton, S. Patel, N. Nguyen, J. Swaffield, D.R. Powell, A. Wilson, and Q. Liu, Modulation of peripheral serotonin levels by novel tryptophan hydroxylase inhibitors for the potential treatment of functional gastrointestinal disorders. J Med Chem, 2008. 51(13): p. 3684-7.

Q. Liu, Q. Yang, W. Sun, P. Vogel, W. Heydorn, X.Q. Yu, Z. Hu, W. Yu, B. Jonas, R. Pineda, V. Calderon-Gay, M. Germann, E. O'Neill, R. Brommage, E. Cullinan, K. Platt, A. Wilson, D. Powell, A. Sands, B. Zambrowicz, and Z.C. Shi, Discovery and characterization of novel tryptophan hydroxylase inhibitors that selectively inhibit serotonin synthesis in the gastrointestinal tract. J Pharmacol Exp Ther, 2008. 325(1): p. 47-55.

B.P. Zambrowicz, C.A. Turner, and A.T. Sands, Predicting drug efficacy: knockouts model pipeline drugs of the pharmaceutical industry. Curr Opin Pharmacol, 2003. 3(5): p. 563-70.

B.P. Zambrowicz and A.T. Sands, Knockouts model the 100 best-selling drugs--will they model the next 100? Nat Rev Drug Discov, 2003. 2(1): p. 38-51.