Profile
International Journal of Clinical Pharmacology & Pharmacotherapy Volume 1 (2016), Article ID 1:IJCPP-118, 3 pages
https://doi.org/10.15344/2456-3501/2016/118
Short Communication
Intelligent Design of Brain-penetrant Compounds Based on Transporter- Conscious Drug Design

Toshihiko Tashima

Tashima Laboratories of Arts and Sciences, 1239-5 Toriyama-cho, Kohoku-ku, Yokohama, Kanagawa 222-0035, Japan
Dr. Toshihiko Tashima, Tashima Laboratories of Arts and Sciences, 1239-5 Toriyama-cho, Kohoku-ku, Yokohama, Kanagawa 222- 0035, Japan; E-mail: tashima_lab@yahoo.co.jp
22 July 2016; 21 September 2016; 23 September 2016
Tashima T (2016) Intelligent Design of Brain-penetrant Compounds Based on Transporter-Conscious Drug Design. Int J Clin Pharmacol Pharmacother 1: 118. doi: https://doi.org/10.15344/2456-3501/2016/118

References

  1. Stenehjem DD, Hartz AM, Bauer B, Anderson GW (2009) Novel and emerging strategies in drug delivery for overcoming the blood–brain barrier, Future Med Chem 1: 1623-1641 [CrossRef] [Google Scholar] [PubMed]
  2. Chen Y, Liu L (2012) Modern methods for delivery of drugs across the blood-brain barrier. Advanced Drug Delivery Reviews 64: 640-665 [CrossRef] [Google Scholar]
  3. International Transporter Consortium, Giacomini KM, Huang SM, Tweedie DJ, Benet LZ, Brouwer KL, et al. (2010) Membrane transporters in drug development. Nat Rev Drug Disc 9: 215-236 [CrossRef] [Google Scholar] [PubMed]
  4. Kimura Y, Morita S, Matsuo M, Ueda K (2007) Mechanism of multidrug recognition by MDR1/ABCB1. Cancer Sci 98: 1303-1308 [CrossRef] [Google Scholar] [PubMed]
  5. Tashima T (2015) Intriguing possibilities and beneficial aspects of transporter-conscious drug design. Bioorg Med Chem 23: 4119-4131 [CrossRef] [Google Scholar] [PubMed]
  6. Nakanishi T, Tamai I (2011) Solute carrier transporters as targets for drug delivery and pharmacological intervention for chemotherapy. J Pharm Sci 100: 3731 [CrossRef] [Google Scholar] [PubMed]
  7. Mehta DC, Short JL, Nicolazzo JA (2013) Memantine transport across the mouse blood-brain barrier is mediated by a cationic influx H+ antiporter. Mol Pharm 10: 4491-4498 [CrossRef] [Google Scholar] [PubMed]
  8. André P, Debray M, Scherrmann JM, Cisternino S (2009) Clonidine transport at the mouse blood-brain barrier by a new H+ antiporter that interacts with addictive drugs. J Cereb Blood Flow Metab 29: 1293-1304.9 [CrossRef] [Google Scholar] [PubMed]
  9. Shimomura K, Okura T, Kato S, Couraud PO, Schermann JM, et al. (2013) Functional expression of a proton-coupled organic cation (H+/OC) antiporter in human brain capillary endothelial cell line hCMEC/D3, a human bloodbrain barrier model. Fluids Barriers CNS 10: 8 [CrossRef] [Google Scholar] [PubMed]
  10. Redrobe JP, Rasmussen LK, Christoffersen CT, Bundgaard C, Jørgensen M (2015) Characterisation of Lu AF33241: A novel, brain-penetrant, dual inhibitor of phosphodiesterase (PDE) 2A and PDE10A.Eur J Pharm 761: 79-85 [CrossRef] [Google Scholar] [PubMed]
  11. Sasmal PK, Krishna C V, Adabala S, Roshaiah SS, Rawoof M, et al. (2015) Optimisation of in silico derived 2-aminobenzimidazole hits as unprecedented selective kappa opioid receptor agonists. Bioorg Med Chem Lett 25: 887-892 [CrossRef] [Google Scholar] [PubMed]
  12. Nirogi R, Mohammed AR, Shinde AK, Bogaraju N, Gagginapalli SR, et al. (2015) Discovery of novel spiro 1,3,4-thiadiazolines as potent, orally bioavailable and brain penetrant KSP inhibitors. Eur J Med Chem 103: 289-301 [CrossRef] [Google Scholar] [PubMed]
  13. Mansoor UF, Angeles AR, Dai C, Yang L, Vitharana D, et al. (2015) Discovery of novel spiro 1,3,4-thiadiazolines as potent, orally bioavailable and brain penetrant KSP inhibitors. Bioorg Med Chem 23: 2424-2434 [CrossRef] [Google Scholar] [PubMed]
  14. Patel S, Harris SF, Gibbons P, Deshmukh G, Gustafson A, et al. (2015) Scaffold-Hopping and Structure-Based Discovery of Potent, Selective, And Brain Penetrant N-(1H-Pyrazol-3-yl)pyridin-2-amine Inhibitors of Dual Leucine Zipper Kinase (DLK, MAP3K12). J Med Chem 58: 8182-8199 [CrossRef] [Google Scholar] [PubMed]
  15. Ariza M, Kolb HC, Moechars D, Rombouts F, Andrés JI (2015) J Med Chem 58: 4365-4382
  16. Wang X, Li J, Xu C, Li Y, Gong T, et al. (2014) Scopine as a Novel Brain- Targeting Moiety Enhances the Brain Uptake of Chlorambucil. Bioconjugate Chem 25: 2046-2054 [CrossRef] [Google Scholar] [PubMed]
  17. Li Y, Zhou Y, Qi B, Gong T, Sun X, et al. (2014) Brain-specific delivery of dopamine mediated by n,n-dimethyl amino group for the treatment of Parkinson's disease. Mol Pharm 11: 3174-3185 [CrossRef] [Google Scholar] [PubMed]