Recent advances in the prediction of blood-brain partitioning from molecular structure

Journal of Pharmaceutical Sciences

Volumn 92, Issue 2, 2003, Pages 360-370

  Lobell, Mario ^a,c   Molnár, László ^b   Keserü, György M ^b  

^a British Biotech Pharmaceuticals Ltd   (United Kingdom)

^b GEDEON RICHTER LTD   (Hungary)

^c OSI Pharmaceuticals   (United Kingdom)

Author keywords

ACD log D Suite; Blood brain barrier penetration; Blood brain partitioning; Cerius2; CNS drugs; In silico; Log BB prediction

Indexed keywords

CENTRAL NERVOUS SYSTEM AGENTS;

ARTICLE; BLOOD BRAIN BARRIER; COMPUTER PROGRAM; DIAGNOSTIC ACCURACY; DRUG DETERMINATION; DRUG PENETRATION; DRUG STRUCTURE; PARTITION COEFFICIENT; PREDICTION;

EID: 0037309942     PISSN: 00223549     EISSN: None     Source Type: Journal    
DOI: 10.1002/jps.10282     Document Type: Article

References (31)

1. Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. 1997. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv 23:3-25.
2. Clark DE. 2001. Prediction of intestinal absorption and blood-brain barrier penetration by computational methods. Comb Chem High Throughput Screen 4:477-496.
3. Young RC, Mitchell RC, Brown TH, Ganellin CR, Griffiths R, Jones M, Rana KK, Saunders D, Smith IR, Sore NE, Wilks TJ. 1988. Development of a new physicochemical model for brain penetration and its application to the design of centrally acting H2 receptor histamine antagonist. J Med Chem 31: 656-671.
4. Hansch C, Bjorkroth JP, Leo A. 1987. Hydrophobicity and central nervous system agents: On the principle of minimal hydrophobicity in drug design. J Pharm Sci 76:663-687.
5. Norinder U, Sjoberg P, Ostenberg T. 1998. Theoretical calculation and prediction of brain-blood partitioning of organic solutes using Molsurf parameterization and PLS statistics. J Pharm Sci 87: 952-959.
6. Abraham MH, Chadha HS, Mitchel RC. 1994. Hydrogen bonding. 33. Factors that influence the distribution of solutes between blood and brain. J Pharm Sci 83:1257-1268.
7. Abraham MH, Chadha HS, Mitchel RC. 1995. Hydrogen bonding. 36. Determination of blood brain distribution using octanol-water partition coefficients. Drug Des Discuss 13:123-131.
8. Ajay, Bemis GW, Murcko MA. 1999. Designing Libraries with CNS Activity. J Med Chem 42:4942-4951.
9. Keserü GM, Molnár L. 2000. A neural network based virtual high throughput screening test for the prediction of CNS activity. Comb Chem HTS 3:535-540.
10. Palm K, Stenberg P, Luthman K, Artursson P. 1997. Polar molecular surface properties predict the intestinal absorption of drugs in human. Pharm Res 14:568-571.
11. Lombardo F, Blake JF, Curatolo WJ. 1996. Computation of brain-blood partitioning of organic solutes via free energy calculation. J Med Chem 39:4750-4755.
12. Keserü GM, Molnár L. 2001. High-throughput prediction of blood-brain partitioning: A thermodynamic approach. J Chem Inf Comput Sci 41:120-128.
13. Pardridge WM. 1998. CNS drug design based on principles of blood-brain barrier transport. J Neurochem 70:1781-1792.
14. Abraham MH, Chadha HS, Mitchel RC. 1995. Hydrogen bonding. 36. Determination of blood brain distribution using octanol-water partition coefficients. Drug Des Discuss 13:123-131.
15. Luco JM. 1999. Prediction of the brain-blood distribution of a large set of drugs from structurally derived descriptors using partial least-squares (PLS) modeling. J Chem Inf Comput Sci 39:396-404.
16. Kelder J, Grootenhuis PDJ, Bayada DM, Delbressine LPC, Ploemen JP. 1999. Polar molecular surface as a dominating determinant for oral absorption and brain penetration of drugs. Pharm Res 16:1514-1519.
17. Salminen T, Pulli A, Taskinen J. 1997. Relationship between immobilised artificial membrane chromatographic retention and the brain penetration of structurally diverse drugs. J Pharm Biomed Anal 15:469-477.
18. Clark DE. 1999. Rapid calculation of polar molecular surface area and its application to the prediction of transport phenomena. 2. Prediction of blood-brain barrier penetration. J Pharm Sci 88: 815-821.
19. Crivori P, Cruciani G, Carrupt P-A, Testa B. 2000. Predicting blood-brain barrier permeation from three-dimensional molecular structure. J Med Chem 43:2204-2216.
20. Platts JA, Abraham MH, Zhao YH, Hersey A, Ijaz L, Butina D. 2001. Correlation and prediction of a large blood-brain distribution data set - an LFER study. Eur J Med Chem 36:719-730.
21. The C2-ADME information sheet available from the Accelrys website (www.accelrys.com).
22. Egan WJ, Merz KM Jr, Baldwin JJ. 2000. Prediction of drug absorption using multivariate statistics. J Med Chem 43:3867-3877.
23. Egan WJ, Lauri G. 2001. Prediction of molecular polar surface area and bioabsorption. International Patent Application WO 01/79841 A1.
24. Clark DE. 1999. Rapid calculation of polar surface area and its application to the prediction of transport phenomena. 1. Prediction of intestinal absorption. J Pharm Sci 88:807-814.
25. Fehér M, Sourial E, Schmidt JM. 2000. A simple model for the prediction of blood-brain partitioning. Int J Pharm 201:239-247.
26. Cruciani G, Pastor M, Guba W. 2000. VolSurf: A new tool for the pharmacokinetic optimization of lead compounds. Int J Pharm 11 Suppl:S29-S39.
27. van de Waterbeemd H, Camenisch G, Folkers G, Chretien JR, Raevsky OA. 1998. Estimation of blood-brain barrier crossing of drugs using molecular size and shape, and H-bonding descriptors. J Drug Target 6:151-165.
28. Fischer H, Gottschlich R, Seelig A. 1998. Blood-brain barrier permeation: Molecular parameters governing passive diffusion. J Membr Biol 165: 201-211.
29. Rohrbaugh RH, Jurs PC. 1987. Descriptions of molecular shape applied in studies of structure/activity and structure/property relationships. Anal Chim Acta 199:99-109.
30. Hopfinger AJ. 1973. Conformational properties of macromolecules. New York: Academic Press.
31. Hopfinger AJ. 1980. In: Walters DB, editor. Safe handling of chemical carcinogens, mutagens, teratogens and highly toxic substances. Ann Arbor, MI: Ann Arbor Press, p. 385.