415
Views
0
CrossRef citations to date
0
Altmetric
Review

Rational Application of Drug Promiscuity in Medicinal Chemistry

&
Pages 1835-1851 | Received 20 Jan 2018, Accepted 04 May 2018, Published online: 18 Jul 2018

References

  • Frank SD . Target-based drug discovery: is something wrong?Drug Discov. Today10 (2), 139 – 147 (2005).
  • Chartier M Morency LP Zylber MI Najmanovich RJ . Large-scale detection of drug off-targets: hypotheses for drug repurposing and understanding side-effects. BMC Pharmacol. Toxicol.18, 18 (2017).
  • Guo ZR . Drug promiscuity. Acta Pharm. Sin.46 (4), 361 – 369 (2011).
  • Howard HR Lowe JA Seeger TF et al. 3-benzisothiazolylpiperazine derivatives as potential atypical antipsychotic agents. J. Med. Chem.39 (1), 143 – 148 (1996).
  • Hu Y Bajorath J . High-resolution view of compound promiscuity [version 2; referees: 3 approved]. F1000Res.2, 144 (2013).
  • Jasial S Hu Y Bajorath J . Determing the degree of promiscuity of extensively assayed compounds. PLoS ONE11 (4), e0153873 (2016).
  • Zhou Z Vorperian VR Gong Q Zhang S January CT . Block of HERG potassium channels by the antihistamine astemizole and its metabolites desmethylastemizole and norastemizole. J. Cardiovasc. Electr.10 (6), 836 – 843 (1999).
  • Reichert JM . Trends in development and approval times for new therapeutics in the United States. Nat. Rev. Drug Discov.2 (9), 695 – 702 (2003).
  • Ashburn TT Thor KB . Drug repositioning: identifying and developing new uses for existing drugs. Nat. Rev. Drug Discov.3 (8), 673 – 683 (2004).
  • Ghofrani HA Osterloh IH Grimminger F . Sildenafil: from angina to erectile dysfunction to pulmonary hypertension and beyond. Nat. Rev. Drug Discov.5 (8), 689 – 702 (2006).
  • Fernandez A . Is there a case for selectively promiscuous anticancer drugs?Drug Discov. Today14 (1), 1 – 5 (2009).
  • Cumming JG Raymond V Finlay M Giordanetto F et al. Potential strategies for increasing drug-discovery productivity. Future Med. Chem.6 (5), 515 – 527 (2014).
  • Hopkins AL Mason JS Overington JP . Can we rationally design promiscuous drugs?Curr. Opin. Struc. Biol.16 (1), 127 – 136 (2006).
  • Tarcasy Á Keserű GM . Contributions of molecular properties to drug promiscuity. J. Med. Chem.56 (5), 1789 – 1795 (2013).
  • Anighoro A Bajorath J Rastelli G . Polypharmacology: challenges and opportunities in drug discovery. J. Med. Chem.57 (19), 7874 – 7887 (2014).
  • Morphy R Rankovic Z . Designed mutiple ligands. An emerging drug discovery paradigm. J. Med. Chem.48 (21), 6523 – 6543 (2005).
  • Korcsmáros T Szalay MS Böde C Kovács IA Csermely P . How to design muti-target drugs: target search options in cellular networks. Expert Opin. Drug Discov.2 (6), 799 – 808 (2007).
  • Ramsay RR Popovic-Nikolic MR Nikolic K Uliassi E Bolognesi ML . A perspective on multi-target drug discovery and design for complex diseases. Clin. Transl. Med.7, 3 (2018).
  • Tan Z Chaudhai R Zhang SX . Polypharmacology in drug development: a minireview of current technologies. ChemMedChem11 (12), 1211 – 1218 (2016).
  • Handler N Buschmann H . Drug Selectivity An Evolving Concept In Medicinal Chemistry.Wiley VCH Verlag GmbH & Co KGaA, Weinheim, Germany, 161 – 206 (2018).
  • Priest BT Erdemli G . Phenotypic screening in the 21st century. Front. Pharmacol.5, 264 (2014).
  • Warchal SJ Unciti-Broceta A Carragher NO . Next generation phenotypic screening. Future Med. Chem.8 (11), 1331 – 1347 (2016).
  • Escobar-Chavez JJ Dominguez-Delgado CL Rodriguez-Cruz IM . Targeting nicotine addiction: the possibility of a therapeutic vaccine. Drug Des. Dev. Ther.5, 211 – 224 (2011).
  • Hackling A Ghosh R Perachon S et al. N-(omega-(4-(2-methoxyphenyl)piperazin-1-yl)alkyl)carboxamides as dopamine D2 and D3 receptor ligands. J. Med. Chem.46 (18), 3883 – 3899 (2003).
  • Mor M Rivara S Lodola A et al. Cyclohexylcarbamic acid 3’- or 4’-substituted biphenyl-3-yl esters as fatty acid amide hydrolase inhibitors: synthesis, quantitative structure-activity relationships, and molecular modeling studies. J. Med. Chem.47 (21), 4998 – 5008 (2004).
  • De Simone A Ruda GF Albani C et al. Applying a multitarget rational drug design strategy: the first set of modulators with potent and balanced activity toward dopamine D3 receptor and fatty acid amide hydrolase. Chem. Commun.50 (38), 4904 – 4907 (2014).
  • Joyce JN Millan MJ . Dopamine D3 receptor antagonists as therapeutic agents. Drug Discov. Today10 (13), 917 – 925 (2005).
  • Peters JU Hert J Bissantz C et al. Can we discover pharmacological promiscuity early in the drug discovery process? Drug Discov. Today 17 (7–8), 325 – 335 (2012).
  • Elias O Kovacs Z Wagner G Nemethy Z Tarcsay A Greiner I . Charting the chemical space around the (iso)indoline scaffold, a comprehensive approach towards multitarget directed ligands. Bioorg. Med. Chem. Lett.26 (17), 4211 – 4215 (2016).
  • Yang EG Mustafa N Tan EC et al. Design and synthesis of janus kinase 2 (JAK2) and histone deacetlyase (HDAC) bispecific inhibitors based on pacritinib and evidence of dual pathway inhibition in hematological cell lines. J. Med. Chem.59 (18), 8233 – 8262 (2016).
  • Albrecht W Unger A Bauer SM Laufer SA . Discovery of N-{4-[5-(4-Fluorophenyl)-3-methyl-2-methylsulfanyl-3H-imidazol-4-yl]-pyridin-2-yl}-acetamide (CBS-3595), a dual p38α MAPK/PDE-4 inhibitor with activity against TNFα-related diseases. J. Med. Chem.60 (13), 5290 – 5305 (2017).
  • Morphy R Rankovic Z . Designing multiple ligands-medicinal chemistry strategies and challenges. Curr. Pharm. Design15 (6), 587 – 600 (2009).
  • Lairmore TC Dou S Howe JR et al. A 1.5-megabase yeast artificial chromosome contig from human chromosome 10q11.2 connecting three genetic loi (Ret, D10S94, and D10S102) closely linked to MEN2A locus. Proc. Natl Acad. Sci. USA90 (2), 492 – 496 (1993).
  • Dar AC Das TK Shokat KM Cagan RL . Chemical genetic discovery of targets and anti-targets for cancer polypharmacology. Nature486 (7401), 80 – 84 (2012).
  • Yu JH Ahn S Kim HJ et al. Polypharmacology of N6-(3-Iodobenzyl)adenosine-5′-N-methyluronamide (IB-MECA) and related A3 Adenosine receptor ligands: peroxisome proliferator activated receptor (PPAR) γ partial agonist and PPARδ antagonist activity suggests their antidiabetic potential. J. Med. Chem.60 (17), 7459 – 7475 (2017).
  • Baell JB Holloway GA . New substructure filters for removal of pan assay interference compounds (PAINS) from screening libraries and for their exclusion in bioassays. J. Med. Chem.53 (7), 2719 – 2740 (2010).
  • Gilberg E Jasial S Stumpfe D Dimova D Bajorath J . Highly promiscuous small molecules from biological screening assays include many pan-assay interference compounds but also candidates for polypharmacology. J. Med. Chem.59 (22), 10285 – 10290 (2016).
  • Klug DM Gelb MH Pollastri MP . Repurposing strategies for tropical disease drug discovery. Bioorg. Med. Chem. Lett.26 (11), 2569 – 2576 (2016).
  • Campillos M Kuhn M Gavin AC Jensen LJ Bork P . Drug target identification using side-effect similarity. Science321 (5886), 263 – 266 (2008).
  • Zhao Z Martin C Fan R Bourne PE Xie L . Drug repurposing to target Ebola virus replication and virulence using structural systems pharmacology. BMC Bioinformatics17, 90 (2016).
  • Ma DL Chan DS Leung CH . Drug repositioning by structure-based virtual screening. Chem. Soc. Rev.42 (5), 2130 – 2141 (2013).
  • Singh N Halliday AC Thomas JM et al. A safe lithium mimetic for bipolar disorder. Nat. Commun.4, 1332 – 1338 (2013).
  • Austin CP Brady LS Insel TR Collins FS . NIH Molecular Libraries Initiative. Science306 (5699), 1138 – 1139 (2004).
  • Chaw SY Majeed AA Dalley AJ Chan A Stein S Farah CS . Epithelial to mesenchymal transition (EMT) biomarkers--E-cadherin, beta-catenin, APC and Vimentin--in oral squamous cell carcinogenesis and transformation. Oral. Oncol.48 (10), 997 – 1006 (2012).
  • Qu Y Gharbi N Yuan X et al. Axitinib blocks Wnt/beta-catenin signaling and directs asymmetric cell division in cancer. Proc. Natl Acad. Sci. USA113 (33), 9339 – 9344 (2016).
  • Kishimoto T Akira S Taga T . Interleukin-6 and its receptor: a paradigm for cytokines. Science258 (5082), 593 – 597 (1992).
  • Li H Liu A Zhao Z et al. Fragment-based drug design and drug repositioning using multiple ligand simultaneous docking (MLSD), identifying celecoxib and template compounds as novel inhibitors of signal transducer and activator of transcription 3 (STAT3). J. Med. Chem.54 (15), 5592 – 5596 (2011).
  • Li H Xiao H Lin L et al. Drug design targeting protein-protein interactions (PPIs) using multiple ligand simultaneous docking (MLSD) and drug repositioning: discovery of raloxifene and bazedoxifene as novel inhibitors of IL-6/GP130 interface. J. Med. Chem.57 (3), 632 – 641 (2014).
  • Pollastri MP Campbell RK . Target repurposing for neglected disease. Future Med. Chem.3 (10), 1307 – 1315 (2011).
  • Parsons M Worthey EA Ward PA Mottram JC . Comparative analysis of the kinomes of three pathogenic trypanosomatids: Leishmania major, Trypanosoma brucei and Trypanosoma cruzi. BMC Genomics6, 127 (2005).
  • Tu XM Kumar P Li ZY Wang CC . Aurora kinase homologue is involved in regulating both mitosis and cytokinesis in Trypanosoma brucei. J. Biol. Chem.281 (14), 9677 – 9687 (2006).
  • Ochiana SO Pandarinath V Wang ZX et al. The human Aurora kinase inhibitor danusertib is a lead compound for anti-trypanosomal drug discovery via target repurposing. Eur. J. Med. Chem.62, 777 – 784 (2013).
  • Patel G Karver CE Behera R et al. Kinase scaffold repurposing for neglected disease drug discovery: discovery of an efficacious, lapatinib-derived lead compound for trypanosomiasis. J. Med. Chem.56 (10), 3820 – 3832 (2013).
  • Guo ZR . Strategy of molecular drug design: activity and druggability. Acta Pharm. Sin.45 (5), 539 – 547 (2010).
  • Bowes J Brown AJ Hamon J et al. Reducing safety-related drug attrition: the use of in vitro pharmacological profiling. Nat. Rev. Drug Discov.11 (12), 909 – 922 (2012).
  • Rothman RB Baumann MH Savage JE et al. Evidence for possible involvement of 5-HT(2B) receptors in the cardiac valvulopathy associated with fenfluramine and other serotonergic medications. Circulation102 (23), 2836 – 2841 (2000).
  • Dosa PI Ward T Walters MA Kim SW . Synthesis of novel analogs of cabergoline: improving cardiovascular safety by removing 5-HT2B receptor agonism. ACS Med. Chem. Lett.4 (2), 254 – 258 (2013).
  • Louvel J Carvalho JF Yu Z et al. Removal of human ether-a-go-go related gene (hERG) K+ channel affinity through rigidity: a case of clofilium analogues. J. Med. Chem.56 (23), 9427 – 9440 (2013).
  • Mei YC Yang BW . Application of amide bioisosteres in the optimization of lead compounds. Prog. Chem.28 (9), 1406 – 1416 (2016).
  • Nair AG Wong MK Shu Y et al. Discovery of CXCR3 antagonists substituted with heterocycles as amide surrogates: improved PK, hERG and metabolic profiles. Bioorg. Med. Chem. Lett.24 (4), 1085 – 1088 (2014).
  • von Kleist L Michaelis S Bartho K et al. Identification of potential off-target toxicity liabilities of catechol-o-methyltransferase inhibitors by differential competition capture compound mass spectrometry. J. Med. Chem.59 (10), 4664 – 4675 (2016).
  • Koster H Little DP Luan P et al. Capture compound mass spectrometry: a technology for the investigation of small molecule protein interactions. Assay Drug Dev. Technol.5 (3), 381 – 390 (2007).
  • Prati F Cavalli A Bolognesi ML . Navigating the chemical space of multi-target directed ligands: from hybrids to fragments in Alzheimer's disease. Molecules21 (4), 466 – 477 (2016).

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.