In vitro measurement of drug efficiency index to aid early lead optimization

Journal of Pharmaceutical Sciences

Volumn 101, Issue 11, 2012, Pages 4155-4169

  Valko, Klara ^a,b   Chiarparin, Elisabetta ^c   Nunhuck, Shenaz ^a,b   Montanari, Dino ^d  

^a GLAXOSMITHKLINE   (United Kingdom)

^b ASTEX PHARMACEUTICALS   (United Kingdom)

^c Aptuit Inc   (United States)

^d H LUNDBECK A S   (Denmark)

Author keywords

ADME; Biomimetics; Drug like properties; HPLC (high performance pressure liquid chromatography); Log P; Phospholipids; Protein binding; Tissue partition

Indexed keywords

ABACAVIR; ACEBUTOLOL; ACRIVASTINE; ALFUZOSIN; ALOSETRON; AMFEBUTAMONE; AMITRIPTYLINE; AMLODIPINE BESYLATE; AMPRENAVIR; ANASTROZOLE; APREPITANT; ARIPIPRAZOLE; BENDROFLUMETHIAZIDE; BEZAFIBRATE; BICALUTAMIDE; BUSPIRONE; CAFFEINE; CANDESARTAN HEXETIL; CARBAMAZEPINE; CELECOXIB; CETIRIZINE; CILOSTAZOL; CITALOPRAM; CLOMIPRAMINE; CLONIDINE; DAPSONE; HUMAN SERUM ALBUMIN; PHOSPHOLIPID; SALBUTAMOL SULFATE; UNINDEXED DRUG;

ARTICLE; BIOMIMETICS; CORRELATION COEFFICIENT; DRUG ABSORPTION; DRUG BINDING; DRUG BIOAVAILABILITY; DRUG CLEARANCE; DRUG DISTRIBUTION; DRUG DOSE REGIMEN; DRUG EFFICACY; DRUG EFFICIENCY INDEX; DRUG ELIMINATION; DRUG EXCRETION; DRUG METABOLISM; DRUG POTENCY; DRUG PROTEIN BINDING; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; IN VITRO STUDY; MASS SPECTROMETRY; MEASUREMENT; PHARMACOLOGICAL PARAMETERS;

EID: 84866357133     PISSN: 00223549     EISSN: 15206017     Source Type: Journal    
DOI: 10.1002/jps.23305     Document Type: Article

References (23)

1. Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. 2001. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev 46:3-26.
2. Veber DF, Johnson SR, Cheng HY, Smith BR, Ward KW, Kopple KD. 2002. Molecular properties that influence the oral bioavailability of drug candidates. J Med Chem 45:2615-2623.
3. Van de Waterbeemd H, Smith DA, Beaumont K, Walker DK. 2001. Property-based design: Optimization of drug absorption and pharmacokinetics. J Med Chem 44:1313-1333.
4. Bade R, Chan H-F, Reynisson J. 2010. Characteristics of known drug space. Natural products, their derivatives and synthetic drugs. Eur J Med Chem 45:5646-5652.
5. Leeson PD, Empfield JR. 2010. Reducing the risk of drug attrition associated with physicochemical properties. Ann Rep Med Chem 45:393-407.
6. Hopkins AL, Groom CR. 2004. Ligand efficiency: A useful metric for lead selection. Drug Discov Today 9:430-431.
7. Rees DC, Congreve MC, Murray CW, Carr R. 2004. Fragment-based lead discovery. Nat Rev Drug Discov 3:660-672.
8. Abad-Zapatero C, Metz JT. 2005. Ligand efficiency indices as guidepost for drug discovery. Drug Discov Today 10:464-469.
9. Leeson PD, Springthorpe B. 2007. The influence of drug-like concepts on decision-making in medicinal chemistry. Nat Rev Drug Discov 6:881-890.
10. Braggio S, Montanari D, Rossi T, Ratti E. 2010. Drug efficiency: A new concept to guide lead optimization programs towards the selection of better clinical candidates. Exp Opin Drug Discov 5:609-618.
11. Stepensky D. 2011. Use of unbound volumes of drug distribution in pharmacokinetic calculations. Eur J Pharm Sci 42:91-98.
12. Montanari D, Chiarparin E, Gleeson MP, Braggio S, Longhi R, Valko K, Rossi T. 2011. Application of drug efficiency index in drug discovery: A strategy towards low therapeutic dose. Expert Opin Drug Discov 6:913-920.
13. Hughes JD, Blagg J, Price DA, Bailey S, DeCrescenzo GA, Devraj RV, Ellsworth E, Fobia YM, Gibbs ME, Gilles RW, Greene N, Huang E, Krieger-Burke T, Loesel J, Wager T, Whiteley L, Zhang Y. 2008. Physicochemical drug properties associated with in vivo toxicological outcomes. Bioorg Med Chem Lett 18:4872-4875.
14. Valkó K. 2004. Application of high-performance liquid chromatography based measurements of lipophilicity to model biological distribution. J Chromatogr A 1037:299-310.
15. Valkó KL, Nunhuck SB, Hill AP. 2011. Estimating unbound volume of distribution and tissue binding by in vitro HPLC-based human serum albumin and immobilized artificial membrane-binding measurements. J Pharm Sci 100:849-862.
16. Valkó K, Nunhuck S, Bevan C, Abraham MH, Reynolds DP. 2003. Fast gradient HPLC method to determine compounds binding to human serum albumin. Relationships with octanol/water and immobilized artificial membrane lipophilicity. J Pharm Sci 92:2236-2248.
17. Hollósy F, Valkó K, Hersey A, Nunhuck S, Kèri Gy, Bevan C. 2006. Estimation of volume of distribution in humans from high throughput HPLC-based measurements of human serum albumin binding and immobilized artificial membrane partitioning. J Med Chem 49:6958-6971.
18. Source of in vivo data pXC50 and drug efficiency data: Drugdex, Martindales, PDR, Index Nominium, PubMed, RXList databases.
19. Smith DA, Kerns EH. 2010. The effect of plasma protein binding on in vivo efficacy: Misconceptions in drug discovery. Nat Rev Drug Discov 9:929-939.
20. Lombardo R, Obach RS, Di Capua FM, Bakken GA, Lu J, Potter DM, Gao F, Miller MD, Zhang Y. 2006. Hybrid mixture discriminant analysis-random forest computational model for the prediction of volume of distribution of drugs in human. J Med Chem 49:2262-2267.
21. Tarcsay Á, Nyíri K, Keseru Gy. 2012. Impact of lipophilic efficiency on compound quality. J Med Chem 55:1252-1260.
22. Benet LZ, Galeazzi RL. 1979. Noncompartmental determination of the volume of distribution in steady-state. J Pharm Sci 68:1071-1074.
23. Benet LZ. 2010. Clearance (nèe Rowland) concepts: A downdate and an update. J Pharmacokinet Pharmacodyn 37:529-539.