The importance of plasma protein binding in drug discovery

Bibliography

• TAYLOR D: Fewer new drugs from the pharmaceutical industry. Br. Med. J. (2003) 326:408-409.
   PubMed Web of Science ®Google Scholar
• LIN JH: Challenges in drug discovery: lead optimization and prediction of human pharmacokinetics. Biotechnology: Pharmaceutical Aspects (2004) 1:293-325.
   Google Scholar
• WONG H, GROSSMAN SJ, BAI SA et al.: The chimpanzee (pan troglodytes) as pharmacokinetic model for selection of drug candidates: model characterization and application. Drug Metab. Dispos. (2004) 32(12):1359-1369.
   PubMed Web of Science ®Google Scholar
• BALANI SK, MIWA GT, GAN L-S, WU J-T, LEE FW: Strategy of utilizing in vitro and in vivo ADME tools for lead optimization and drug candidate selection. Curr. Top. Med. Chem. (2005) 5:1033-1038.
   PubMed Web of Science ®Google Scholar
• VALKO K, REYNOLDS DP: High-throughput physicochemical and in vitro ADME screening. Am. J. Drug Deliv. (2005) 3:83-100.
   Google Scholar
• RECANATINI M, POLUZZI E, MASETTI M, CAVALLI A, PONTI FD: QT prolongation through HERG k+ channel blockade: current knowledge and strategies for the early prediction during drug development. Med. Res. Rev. (2005) 25(2):133-166.
   PubMed Web of Science ®Google Scholar
• KAPLOWITZ N: Idiosyncratic drug hepatotoxicity. Nat. Rev. Drug Discov. (2005) 4:489-499.
   PubMed Web of Science ®Google Scholar
• PETERS TS: Do preclinical testing strategies help predict human hepatotoxic potentials. Toxicol. Pathol. (2005) 33:146-154.
   PubMed Web of Science ®Google Scholar
• LIN JH: Tissue distribution and pharmacodynamics: a complicated relationship. Curr. Drug Metab. (2006) 7:39-65.
   PubMed Web of Science ®Google Scholar
• PAXTON JW: Alpha1-acid glycoprotein and binding of basic drugs. Methods Find. Exp. Clin. Pharmacol. (1983) 5(9):635-648.
   PubMed Web of Science ®Google Scholar
• OLSON RE, CHRIST DD: Plasma protein binding of drugs. Ann. Rep. Med. Chem. (1996) 31:327-336.
   Web of Science ®Google Scholar
• CHRIST DD, TRAINOR GL: Free drug! The critical importance of plasma protein binding in new drug discovery. Biotechnology: Pharmaceutical Aspects (2004) 1:327-336.
   Google Scholar
• WYNN GH, ZAPOR MJ, SMITH BH et al.: Antiretrovirals, part 1: overview, history, and focus on protease inhibitors. Psychosomatics (2004) 45(3):262-270.
   PubMed Web of Science ®Google Scholar
• BRYANT M, GETMAN D, SMIDT M et al.: SC-52151, a novel inhibitor of the human immunodeficiency virus protease. Antimicrob. Agents Chemother. (1995) 39(10):2229-2234.
   PubMed Web of Science ®Google Scholar
• FISCHL MA, RICHMAN DD, FLEXNER C et al.: Phase I/II study of the toxicity, pharmacokinetics, and activity of the HIV protease inhibitor SC-52151. J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. (1997) 15:28-34.
   PubMedGoogle Scholar
• KAGEYAMA S, ANDERSON BD, HOESTEREY BL et al.: Protein binding of human immunodeficiency virus protease inhibitor KNI-272 and alteration of its in vitro antiretroviral activity in the presence of high concentrations of proteins. Antimicrob. Agents Chemother. (1994) 38(5):1107-1111.
   PubMed Web of Science ®Google Scholar
• LIVINGSTON DJ, PAZHANISAMY S, PORTER DJT, PARTALEDIS JA, TUNG RD, PAINTER GR: Weak binding of VX-478 to human plasma proteins and implications for anti-human immunodeficiency virus therapy. J. Infect. Dis. (1995) 172:1238-1245.
   PubMed Web of Science ®Google Scholar
• BILELLO JA, DRUSANO GL: Relevance of plasma protein binding to antiviral activity and clinical efficacy of inhibitors of human immunodeficiency virus. J. Infect. Dis. (1996) 173:1524-1526.
   PubMed Web of Science ®Google Scholar
• BILELLO JA, BILELLO PA, STELLRECHT K et al.: Human serum α1 acid glycoprotein reduces uptake, intracellular concentration, and antiviral activity of A-80987, an inhibitor of the human immunodeficiency virus type 1 protease. Antimicrob. Agents Chemother. (1996) 40(6):1491-1497.
   PubMed Web of Science ®Google Scholar
• GOLDBERG MR, LO M-W, CHRIST DD et al.: Dup-532, an angiotensin II receptor antagonist: first administration and comparison with losartan. Clin. Pharmacol. Ther. (1997) 61(1):59-69.
   PubMed Web of Science ®Google Scholar
• MAILLARD MP, CENTENO C, FROSTELL-KARLSSON A, BRUNNER HR, BURNIER M: Does protein binding modulate the effect of angiotensin II receptor antagonists? J. Renin Angiotensin Aldosterone Syst. (2001) 2(S1):S54-S58.
   Web of Science ®Google Scholar
• BENET LZ, KROETZ DL, SHEINER LB: Pharmacokinetics: the dynamics of drug absorption, distribution, and elimination. In: Goodman and Gilman’s The Pharmacological Basis of Therapeutics, 9th (edn). Hardman JG, Limbird LE (Eds), McGraw-Hill, New York, USA (1996):10.
   Google Scholar
• QUINLAN GJ, MARTIN GS, EVANS TW: Albumin: biochemical properties and therapeutic potential. Hepatology (2005) 41(6):1211-1219.
   PubMed Web of Science ®Google Scholar
• ISRAILI ZH, DAYTON PG: Human alpha-1-glycoprotein and its interactions with drugs. Drug Metab. Rev. (2001) 33(2):161-235.
   PubMed Web of Science ®Google Scholar
• KREMER JMH, WILTING J, JANSSEN LHM: Drug binding to human alpha-1-acid glycoprotein in health and disease. Pharmacol. Rev. (1988) 40(1):1-47.
   PubMed Web of Science ®Google Scholar
• PACIFICI GM, VIANI A: Methods of determining plasma and tissue binding of drugs. Clin. Pharmacokinet. (1992) 23(6):449-468.
   PubMed Web of Science ®Google Scholar
• WAN H, REHNGREN M: High-throughput screening of protein binding by equilibrium dialysis combined with liquid chromatography and mass spectrometry. J. Chromatogr. A (2006) 1102(1-2):125-134.
   PubMed Web of Science ®Google Scholar
• SINGH SS, MEHTA J: Measurement of drug-protein binding by immobilized human serum albumin-HPLC and comparison with ultrafiltration. J. Chromatogr. B (2006) 834(1-2):108-116.
   PubMed Web of Science ®Google Scholar
• CIMITAN S, LINDGREN MT, BERTUCCI C, DANIELSON UH: Early absorption and distribution analysis of antitumor and anti-AIDS drugs: lipid membrane and plasma protein interactions. J. Med. Chem. (2005) 48(10):3536-3546.
   PubMed Web of Science ®Google Scholar
• KALTENBACH RF, TRAINOR G, GETMAN D et al.: DPC-681 and DPC-684: potent, selective inhibitors of human immunodeficiency virus protease active against clinically relevant mutant variants. Antimicrob. Agents Chemother. (2001) 45(11):3021-3028.
   PubMed Web of Science ®Google Scholar
• KALTENBACH RF, PATEL M, WALTERMIRE RE et al.: Synthesis, antiviral activity and pharmacokinetics of P1/P1′ substituted 3-aminoindazole cyclic urea HIV protease inhibitors. Bioorg. Med. Chem. Lett. (2003) 13:605-608.
   PubMed Web of Science ®Google Scholar
• COPELAND RA: Determination of serum protein binding affinity of inhibitors from analysis of concentration-response plots in biochemical activity assays. J. Pharm. Sci. (2000) 89:1000-1007.
   PubMed Web of Science ®Google Scholar
• RUSNAK DW, LAI A, LANSING TJ, RHODES N, GILMER TM, COPELAND RA: A simple method for predicting serum protein binding of compounds from IC50 shift analysis for in vitro assays. Bioorg. Med. Chem. Lett. (2004) 14(9):2309-2312.
   PubMed Web of Science ®Google Scholar
• CORBETT JW, KO SS, RODGERS JD et al.: Expanded-spectrum nonnucleoside reverse transcriptase inhibitors inhibit clinically relevant mutant variants of human immunodeficiency virus type 1. Antimicrob. Agents Chemother. (1999) 43(12):2893-2897.
   PubMed Web of Science ®Google Scholar
• ARMBRUSTER C, VORBACH H, STEINDL F, MENYAWI IE: Intracellular concentration of the HIV protease inhibitors indinavir and saquinavir in human endothelial cells. J. Antimicrob. Chemother. (2001) 47:487-490.
   PubMed Web of Science ®Google Scholar
• JONES K, HOGGARD PG, KHOO S, MAHER B, BACK DJ: Effect of alpha-1-acid glycoprotein on the intracellular accumulation of the HIV protease inhibitors saquinavir, ritonavir, and indinavir in vitro. Br. J. Clin. Pharmacol. (2001) 51:99-102.
   PubMed Web of Science ®Google Scholar
• KHOO SH, HOGGARD PG, WILLIAMS I et al.: Intracellular accumulation of human immunodeficiency virus protease inhibitors. Antimicrob. Agents Chemother. (2002) 46(10):3228-3235.
   PubMed Web of Science ®Google Scholar
• ALMOND LM, HOGGARD PG, EDIRISINGHE D, KHOO SH, BACK DJ: Intracellular and plasma pharmacokinetics of efavirenz in HIV-infected individuals. J. Antimicrob. Chemother. (2005) 56:738-744.
   PubMed Web of Science ®Google Scholar
• DROBITCH RK, SWENSSON CK: Therapeutic drug monitoring in saliva, an update. Clin. Pharmacokinet. (1992) 23(5):365-379.
   PubMed Web of Science ®Google Scholar
• KALVASS JC, MAURER TS: Influence of nonspecific brain and plasma binding on CNS exposure: Implications for rational drug discovery. Biopharm. Drug Dispos. (2002) 23:327-338.
   PubMed Web of Science ®Google Scholar
• MAURER TS, DEBARTOLO DB, TESS DA, SCOTT DO: Relationship between exposure and nonspecific binding of thirty-three central nervous system drugs in mice. Drug Dispos. Metab. (2005) 33(1):175-181.
   PubMed Web of Science ®Google Scholar
• SUMMERFIELD SG, STEVENS AJ, CUTLER L et al.: Improving the in vitro prediction of in vivo central nervous system penetration: Integrating permeability, P-glycoprotein efflux, and free fractions in blood and brain. J. Pharmacol. Exp. Ther. (2006) 316(3):1282-1290.
   PubMed Web of Science ®Google Scholar
• WILLIS CL, BRAZELL C, FOSTER AC: Plasma and CSF levels of dizocilpine (mk-801) required for neuroprotection in the quinolinate-injected rat striatum. Eur. J. Pharmacol. (1991) 196:285-290.
   PubMed Web of Science ®Google Scholar
• LI Y-W, HILL G, WONG H et al.: Receptor occupancy of nonpeptide corticotropin-releasing factor 1 antagonist DMP-696: correlation with drug exposure and anxiolytic activity. J. Pharmacol. Exp. Ther. (2003) 305(1):86-96.
   PubMed Web of Science ®Google Scholar
• KHAN S-NH, SHUAIB A: The technique of intracerebral microdialysis. Methods (2001) 23(1):3-9.
   PubMed Web of Science ®Google Scholar
• DE LANGE ECM, DE BOER BAG, BREIMER DD: Microdialysis for pharmacokinetic analysis of drug transport to the brain. Adv. Drug Deliv. Rev. (1999) 36:211-227.
   PubMed Web of Science ®Google Scholar
• SAWCHUK RJ, ELMQUIST WF: Microdialysis in the study of drug transporters in the CNS. Adv. Drug Deliv. Rev. (2000) 45:295-307.
   PubMed Web of Science ®Google Scholar
• EDWARDS JE, BROUWER KR, MCNAMARA PJ: GF-120918, a P-glycoprotein modulator, increases the concentration of unbound amprenavir in the central nervous system in rats. Antimicrob. Agents Chemother. (2002) 46(7):2284-2286.
   PubMed Web of Science ®Google Scholar
• YOO SD, HOLLADAY JH, FINCHER TK, BAUMANN H, DEWEY MJ: Altered disposition and antidepressant activity of imipramine in transgenic mice with elevated alpha-1-acid glycoprotein. J. Pharmacol. Exp. Ther. (1996) 276(3):918-922.
   PubMed Web of Science ®Google Scholar
• BOFFITO M, BACK DJ, BLASCHKE TF et al.: Protein binding in antiretroviral therapies. AIDS Res. Hum. Retroviruses (2003) 19(9):825-835.
   PubMed Web of Science ®Google Scholar
• GAMBACORTI-PASSERINI C, BARNI R, COUTRE PL et al.: Role of alpha1 acid glycoprotein in the in vivo resistance of human bcr–abl+ leukemic cells to the abl inhibitor STI-571. J. Natl. Cancer Inst. (2000) 92(20):1641-1650.
   PubMed Web of Science ®Google Scholar
• JORGENSEN HG, ELLIOTT ME, ALLAN EK, CARR CE, HOLYOAKE TL, SMITH KD: Alpha1-acid glycoprotein expressed in the plasma of chronic myeloid leukemia patients does not mediate significant in vitro resistance to STI-571. Blood (2002) 99(2):713-715.
   PubMed Web of Science ®Google Scholar
• GAMBACORTA-PASSERINI C, COUTRE PL, ZUCCHETI M, D’INCALCI M: Binding of imatinib by alpha1-acid glycoprotein. Blood (2002) 100(1):367-368.
   PubMed Web of Science ®Google Scholar
• JORGENSEN H, ELLIOTT M, PETERSON S, HOLYOAKE T, SMITH K: Further observations on the debated ability of AGP to bind imatinib. Blood (2002) 100(1):368-369.
   Web of Science ®Google Scholar
• GAMBACORTI-PASSERINI C, ZUCCHETTI M, RUSSO D et al.: Alpha1 acid glycoprotein binds to imatinib (STI-571) and substantially alters its pharmacokinetics in chronic myeloid leukemia patients. Clin. Cancer Res. (2003) 9:625-632.
   PubMed Web of Science ®Google Scholar
• LARGHERO J, LEGUAY T, MOURAH S et al.: Relationship between elveated levels of the alpha 1 acid glycoprotein in chronic myelogenous leukemia in blast crisis and pharmacological resistance to imatinib (Gleevec®) in vitro and in vivo. Biochem. Pharmacol. (2003) 66:1907-1913.
   PubMed Web of Science ®Google Scholar
• FUSE E, TANII H, KURATA N et al.: Unpredicted clinical pharmacology of UCN-01 caused by specific binding to human alpha1-acid glycoprotein. Cancer Res. (1998) 58:3248-3253.
   PubMed Web of Science ®Google Scholar
• FUSE E, KUWABARA T, SPARREBOOM A, SAUSVILLE EA, FIGG WD: Review of UCN-01 development: a lesson in the importance of clinical pharmacology. J. Clin. Pharmacol. (2005) 45:394-403.
   PubMed Web of Science ®Google Scholar
• SAUSVILLE EA, ARBUCK SG, MESSMANN R et al.: Phase I trial of 72-hour continuous infusion of UCN-01 in patients with refractory neoplasms. J. Clin. Oncol. (2001) 19(8):2319-2333.
   PubMed Web of Science ®Google Scholar
• BOFFITO M, SCIOLE K, RAITERI R et al.: Alpha1-acid glycoprotein levels in human immunodeficiency virus-infected subjects on antiretroviral regimens. Drug Metab. Dispos. (2002) 30(7):859-860.
   PubMed Web of Science ®Google Scholar
• WOOD M: Plasma protein binding and limitation of drug access to site of action. J. Anesth. (1991) 75(5):721-723.
   Google Scholar
• HERVE F, GOMAS E, DUCHE J-C, TILLEMENT J-P: Evidence for differences in the binding of drugs to the two main genetic variants of human α1-acid glycoprotein. Br. J. Clin. Pharmacol. (1993) 36:241-249.
   PubMed Web of Science ®Google Scholar
• HERVE F, CARON G, DUCHE J-C et al.: Ligand specificity of the genetic variants of human α1-acid glycoprotein: generation of a three-dimensional quantitative structure–activity relationship model for drug binding to the a variant. Mol. Pharmacol. (1998) 54:129-138.
   PubMed Web of Science ®Google Scholar
• POLAND DCW, KULIK W, DIJK WV, HALLEMEESCH MM, JAKOBS C, MEER KD: Distinct glycoforms of human alpha1-acid glycoprotein have comparable synthesis rates: a [13C]valine-labelling study in healthy humans. Glycoconj. J. (2004) 20:99-105.
   PubMed Web of Science ®Google Scholar
• HASHIMOTO S, ASAO T, TAKAHSHI J et al.: Alpha1-acid glycoprotein fucosylation as a marker of carcinoma progression. Cancer (2004) 101(12):2825-2836.
   PubMed Web of Science ®Google Scholar
• WONG AKL, HSIA JC: In vitro binding of propranolol and progesterone to native and desialylated human orosomucoid. Can. J. Biochem. Cell Biol. (1983) 61:1114-1116.
   PubMedGoogle Scholar
• WEBSTER R, LEISHMAN D, WALKER D: Towards a drug concentration effect relationship for qt prolongation and torsades de pointes. Curr. Opin. Drug Discov. Devel. (2002) 5(1):116-126.
   PubMed Web of Science ®Google Scholar
• HAAS DW, STONE J, CLOUGH LA et al.: Steady-state pharmacokinetics of indinavir in cerebrospinal fluid and plasma among adults with human immunodeficiency virus type 1 infection. Clin. Pharmacol. Ther. (2000) 68(4):367-374.
   PubMed Web of Science ®Google Scholar
• KIM RB, FROMM MF, WANDEL C, LEAKE B, WOOD AJJ, RODEN DM: The drug transporter P-glycoprotein limits oral absorption and brain entry of HIV-1 protease inhibitors. J. Clin. Investig. (1998) 101(2):389-294.
   Google Scholar
• GESTWICKI JE, CRABTREE GR, GRAEF IA: Harnessing chaperones to generate small-molecule inhibitors of amyloid beta aggregation. Science (2004) 306:865-869.
   PubMed Web of Science ®Google Scholar
• LIN JH, YAMAZAKI M: Clinical relevance of P-glycoprotein in drug therapy. Drug Metab. Rev. (2003) 35(4):417-454.
   PubMed Web of Science ®Google Scholar
• FISCHER V, EINOLF JJ, COHEN D: Efflux transporters and their clinical relevance. Mini Rev. Med. Chem. (2005) 5(2):183-195.
   PubMed Web of Science ®Google Scholar
• MONTFOORT JEV, HAGENBUCH B, GROOTHUIS GMM, KOEPSELL H, MEIER PJ, MEIJER DKF: Drug uptake systems in liver and kidney. Curr. Drug Metab. (2003) 4(3):185-211.
   PubMed Web of Science ®Google Scholar
• DANTZIG AH, HILLGREN KM, ALWIS DPD: Drug transporters and their role in tissue distribution. Ann. Rep. Med. Chem. (2004) 39:279-291.
   Web of Science ®Google Scholar
• NOZAWA T, MINAMI H, SUGIURA S, TSUJI A, TAMAI I: Role of organic anion transporter oatp1b1 (OATP-C) in hepatic uptake of irinotecan and its active metabolite, 7-hydroxycamptothecin: In vitro evidence and effect of single nucleotide polymorphisms. Drug Metab. Dispos. (2005) 33(3):434-439.
   PubMed Web of Science ®Google Scholar
• DEGUCHI Y, NOZAWA K, YAMADA S, YOKOYAMA Y, KIMURA R: Quantitative evaluation of brain distribution and blood–brain barrier efflux transport of probenecid in rats by microdialysis: possible involvement of the monocarboxylic acid transport system. J. Pharmacol. Exp. Ther. (1997) 280(2):551-560.
   PubMed Web of Science ®Google Scholar
• ESKILD W, KINDBERG GM, SMEDSROD B, BLOMHOFF R, NORUM KR, BERG T: Intracellular transport of formaldehyde-treated serum albumin in liver endothelial cells after uptake via scavenger receptors. Biochem. J. (1989) 258:511-520.
   PubMed Web of Science ®Google Scholar
• WEISIGER R, GOLLAN J, OCKNER R: Receptor for albumin on the liver cell surface may mediate uptake if fatty acids and other albumin-bound substances. Science (1981) 211(6):1048-1051.
   PubMed Web of Science ®Google Scholar
• RAJARAMAN G, ROBERTS MS, HUNG D, WANG GQ, BURCZYNSKI FJ: Membrane binding proteins are the major determinants for the hepatocellular transmembrane flux of long-chain fatty acids bound to albumin. Pharm. Res. (2005) 11:1793-1804.
   Google Scholar
• ANDREASSEN TK: The role of plasma-binding proteins in the cellular uptake of lipophilic vitamins and steroids. Horm. Metab. Res. (2006) 38:279-290.
   PubMed Web of Science ®Google Scholar
• DESAI N, TRIEU V, YAO Z et al.: Increased antitumor activity, intratumor paclitaxel concentrations, and endothelial cell transport of cremophor-free, albumin-bound paclitaxel, ABI-007, compared with cremophor-based paclitaxel. Clin. Cancer Res. (2006) 12(4):1317-1324.
   PubMed Web of Science ®Google Scholar
• TRAN A, REY E, PONS G et al.: Influence of stiripentol on cytochrome P450-mediated metabolic pathways in humans: in vitro and in vivo comparison and calculation of in vivo inhibition constants. Clin. Pharmacol. Ther. (1997) 62(5):490-504.
   PubMed Web of Science ®Google Scholar
• TANG C, LIN Y, RODRIGUES D, LIN JH: Effect of albumin on phenytoin and tolbutamide metabolism in human liver microsomes: an impact of more than protein binding. Drug Metab. Dispos. (2002) 30(6):648-654.
   PubMed Web of Science ®Google Scholar
• PIMPANEAU V, MIDOUX P, DURAND G, BAETSELIER PD, MONSIGNY M, ROCHE A-C: Endocytosis of α1-acid glycoprotein variants and of neoglycoproteins containing mannose derivatives by a mouse hybridoma cell line (2c11-12). Comparison with mouse peritoneal macrophages. Glycoconj. J. (1989) 6:561-574.
   PubMed Web of Science ®Google Scholar
• JONES DR, HALL SD, JACKSON EK, BRANCH RA, WILKINSON GR: Brain uptake of benzodiazepines: effects of lipophilicity and plasma protein binding. J. Pharmacol. Exp. Ther. (1988) 245(2):816-822.
   PubMed Web of Science ®Google Scholar
• TERASAKI T, PARDRIDGE WM, DENSON DD: Differential effect of plasma protein binding of bupivacaine on its in vivo transfer into the brain and salivary gland of rats. J. Pharmacol. Exp. Ther. (1986) 239(3):724-729.
   PubMed Web of Science ®Google Scholar
• MANDULA H, PAREPALLY JMR, FENG R, SMITH QR: Role of site-specific binding to plasma albumin in drug availability to brain. J. Pharmacol. Exp. Ther. (2006) 317(2):667-675.
   PubMed Web of Science ®Google Scholar
• LJUNG B, BAMBERG K, DAHLLOF B et al.: AZ-242, a novel PPARα/γ agonist with beneficial effects on insulin resistance and carbohydrate and lipid metabolism in ob/ob mice and obese Zucker rats. J. Lipid Res. (2002) 43:1855-1863.
   PubMed Web of Science ®Google Scholar
• ERICSSON H, HAMREN B, BERGSTRAND S et al.: Pharmacokinetics and metabolism of tesaglitazar, a novel dual-acting peroxisome proliferator-activated receptor alpha/gamma agonist, after a single oral and intravenous dose. Drug Metab. Dispos. (2004) 32(9):932-929.
   Google Scholar
• SCHAFER-KORTING K, KORTING HC, RITTLER W, OBERMULLER W: Influence of serum protein binding on the in vitro activity of antifungal agents. Infection (1995) 23(5):292-297.
   PubMed Web of Science ®Google Scholar
• COWART M, FAGHIH R, CURTIS MP et al.: 4-(2-[2-(2(R)-methylpyrrolidin- 1-yl)ethyl)]benzofuran-5-yl)benzonitrile and related 2-aminoethylbenzofuran H3 receptor antagonists potently enhance cognition and attention. J. Med. Chem. (2005) 48(1):38-55.
   PubMed Web of Science ®Google Scholar
• HERON NM, ANDERSON M, BLOWERS DP et al.: SAR and inhibitor complex structure determination of a novel class of potent and specific aurora kinase inhibitors. Bioorg. Med. Chem. Lett. (2006) 16:1320-1323.
   PubMed Web of Science ®Google Scholar
• KIM PR, IYENGAR R, SOUERS AJ et al.: Discovery and characterization of aminopiperidiencoumarin melanin concentrating hormone receptor 1 antagonists. J. Med. Chem. (2005) 48(19):5888-5891.
   PubMed Web of Science ®Google Scholar
• STAUFFER KJ, WILLIAMS PD, SELNICK HG et al.: 9-Hydroxyazafluorenes and their use in thrombin inhibitors. J. Med. Chem. (2005) 48(7):2282-2293.
   PubMed Web of Science ®Google Scholar
• QUAN ML, LAM PYS, HAN Q et al.: Discovery of 1-(3′-Aminobenzisoxazol-5′ -yl)-3-trifluoromethyl-n-[2-fluoro-4-[(2′- dimethylaminomethyl)imidazol-1-yl] phenyl]-1H-pyrazol-5-carboxyamide hydrochloride (razaxaban), a highly potent, selective, and orally bioavailable Factor Xa inhibitor. J. Med. Chem. (2005) 48(6):1729-1744.
   PubMed Web of Science ®Google Scholar
• PEVARELLO P, BRASCA MG, ORSINI P et al.: 3-Aminopyrazole inhibitors of cdk2/cyclin A as antitumor agents. 2. Lead optimization. J. Med. Chem. (2005) 48(8):2944-2956.
   PubMed Web of Science ®Google Scholar
• PEVARELLO P, BRASCA MG, AMICI R et al.: 3-Aminopyrazole inhibitors of cdk2/cyclin A as antitumor agents. 1. Lead finding. J. Med. Chem. (2004) 48(13):3367-3380.
   Google Scholar
• JUNG FH, PASQUET G, BREMPT CL-VD et al.: Discovery of novel and potent thiazoloquinazolines as selective aurora A and B kinase inhibitors. J. Med. Chem. (2006) 49(3):955-970.
   PubMed Web of Science ®Google Scholar
• MCKERRECHER D, ALLEN JV, CAULKETT PWR et al.: Design of a potent, soluble glucokinase activator with excellent in vivo efficacy. Bioorg. Med. Chem. Lett. (2006) 16:2705-2709.
   PubMed Web of Science ®Google Scholar
• ZHI C, LONG Z, MANIKOWSKI A et al.: Synthesis and antibacterial activity of 3-substituted-6-(3-ethyl-4-methylanilino)uracils. J. Med. Chem. (2005) 48(22):7063-7074.
   PubMed Web of Science ®Google Scholar
• PEI Z, LI X, LONGNECKER K et al.: Discovery, structure–activity relationship, and pharmacological evaluation of (5-substituted-pyrrolidinyl-2-carbonyl)-2- cyanopyrrolidines as potent dipeptidyl peptidase IV inhibitors. J. Med. Chem. (2006) 49(12):3520-3535.
   PubMed Web of Science ®Google Scholar
• EDMUNDSON SC, MASTRACCHIO A, MATHVINK RJ et al.: (2S,3S)-3-Amino-4-(3,3-difluoropyrrolidin-1-yl)-N,N-dimethyl-4-oxo-2-(4-[1,2,4] triazolo[1,5-a]-pyridin-6-ylphenyl) butanamide: a selective alpha-amino amide dipeptidyl peptidase IV inhibitor for the treatment of Type 2 diabetes. J. Med. Chem. (2006) 49(12):3614-3627.
   PubMed Web of Science ®Google Scholar
• ELLIOTT RL, OLIVER RM, HAMMOND M et al.: In vitro and in vivo characterization of 3-{2-[6-(2-tert-butoxyethoxy)pyridin-3-yl]-1H-imidazo-4-yl}benzonitrile hydrochloride salt, a potent and selective NPY5 receptor antagonist. J. Med. Chem. (2003) 46:670-673.
   PubMed Web of Science ®Google Scholar
• KRATOCHWIL NA, HUBER W, MULLER F, KANSY M, GERBER PR: Predicting plasma protein binding of drugs: a new approach. Biochem. Pharmacol. (2002) 64:1355-1374.
   PubMed Web of Science ®Google Scholar
• YAMAZAKI K, KANAOKA A: Computational prediction of the plasma protein binding percent of diverse pharmaceutical compounds. J. Pharm. Sci. (2004) 93(6):1480-1494.
   PubMed Web of Science ®Google Scholar
• ERMONDI G, LORENTI M, CARON G: Contribution of ionization and lipophilicity to drug binding to albumin: a preliminary step toward biodistribution prediction. J. Med. Chem. (2004) 47(16):3949-3961.
   PubMed Web of Science ®Google Scholar
• AURELI L, CRUCIANI G, CESTA MC, ANACARDIO R, SIMONE LD, MORICONI A: Predicting human serum albumin affinity of interleukin-8 (CXCL8) inhibitors by 3D-QSPR approach. J. Med. Chem. (2005) 48(7):2469-2479.
   PubMed Web of Science ®Google Scholar
• LIU J, YANG L, LI Y, PAN D, HOPFINGER AJ: Prediction of plasma protein binding of drugs using Kier-Hall valence connectivity indices and 4D-fingerprint molecular similarity analyses. J. Comput. Aided Mol. Des. (2005) 19:567-583.
   PubMed Web of Science ®Google Scholar
• GUNTURI SG, NARAYANAN R, KHANDELWAL A: In silico ADME modeling 2: computational models to predict human serum albumin binding affinity using ant colony systems. Bioorg. Med. Chem. (2006) 14:4118-4129.
   PubMed Web of Science ®Google Scholar
• LIU J, YANG L, LI Y, PAN D, HOPFINGER AJ: Constructing plasma protein binding model based on a combination of cluster analysis and 4D-fingerprint molecular similarity analyses. Bioorg. Med. Chem. (2006) 14:611-621.
   PubMed Web of Science ®Google Scholar
• MAO H, HAJDUK PJ, CRAIG R, BELL R, BORRE T, FESIK SW: Rational design of diflunisal analogues with reduced affinity for human serum albumin. J. Am. Chem. Soc. (2001) 123(43):10429-10435.
   PubMed Web of Science ®Google Scholar