Honors & Awards

  • MIPS Retreat Poster Prize, Molecular Imaging Program at Stanford, Stanford University School of Medicine (2015)
  • Commercialisation Training Scheme Scholarship, The University of Sydney (2010-2011)
  • John A. Lamberton Award, The University of Sydney (2007-2008)
  • Vice-Chancellor's Award for Support of the Student Experience, The University of Sydney (2007)
  • University Postgraduate Award in Medicinal Chemistry, The University of Sydney (2006-2010)
  • Agnes Campbell Award for Excellence in Organic Synthesis, The University of Sydney (2006, 2007, 2008, 2009)

Boards, Advisory Committees, Professional Organizations

  • Advisory Board Member, Stanford University School of Medicine Career Center (2016 - Present)
  • Editorial Advisory Board Member, Drug Testing and Analysis (Wiley) (2016 - Present)
  • Member, American Chemical Society (2014 - Present)
  • Member, MIPS Retreat Organizing Committee (2014 - 2014)
  • Member, Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists (2010 - Present)
  • Member, Royal Australian Chemical Institute (2005 - Present)

Professional Education

  • Bachelor of Science, University Of Sydney (2006)
  • Doctor of Philosophy, University Of Sydney (2011)

Stanford Advisors


  • Sam Banister, Mark Coster, Michael Kassiou. "Australia Patent AU2007905694 Method Of Treating Brain Disorders", The University of Sydney, Oct 17, 2007

All Publications

  • The Recent Development of alpha(7) Nicotinic Acetylcholine Receptor (nAChR) Ligands as Therapeutic Candidates for the Treatment of Central Nervous System (CNS) Diseases CURRENT PHARMACEUTICAL DESIGN Beinat, C., Banister, S. D., Herrera, M., Kassiou, M. 2016; 22 (14): 2134-2151


    Homomeric α7 nicotinic acetylcholine receptors (nAChRs) are implicated in the regulation of cognitive processes such as memory and attention and have potential as therapeutic targets for the treatment of the cognitive deficits associated with schizophrenia. Though numerous α7 nAChR agonists have been developed, and several have progressed to clinical trials, these are derived from few common chemotypes. Consequently, many of these α7 nAChR clinical candidates share unfavorable side-effect profile. SEN12333 represents a novel chemotype for the development of α7 nAChR agonists, and exploration of this scaffold has produced structurally diverse ligands with promising pharmacological properties. This review will summarize structure-affinity and -activity relationships surrounding analogs of SEN12333.

    View details for DOI 10.2174/1381612822666160127114125

    View details for Web of Science ID 000375146900016

    View details for PubMedID 26818858

  • Comparative Evaluation of Three TSPO PET Radiotracers in a LPS-Induced Model of Mild Neuroinflammation in Rats Molecular Imaging and Biology Sridharan, S., Lepelletier, F., Trigg, W., Banister, S., Reekie, T., Kassiou, M., Gerhard, A., Hinz, R., Boutin, H. 2016
  • Derivatives of the pyrazolo[1,5-a]pyrimidine acetamide DPA-713 as translocator protein (TSPO) ligands and pro-apoptotic agents in human glioblastoma European Journal of Pharmaceutical Sciences Werry, E. L., King, V. A., Barron, M. L., Banister, S. D., Sokias, R., Kassiou, M. 2016
  • Ether analogues of DPA-714 with subnanomolar affinity for the translocator protein (TSPO) EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY Banister, S. D., Beinat, C., Wilkinson, S. M., Shen, B., Bartoli, C., Selleri, S., Da Pozzo, E., Martini, C., Chin, F. T., Kassiou, M. 2015; 93: 392-400


    Sixteen new phenyl alkyl ether derivatives (12, 14-28) of the 5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-ylacetamide (DPA) class were synthesized and evaluated in a competition binding assay against [(3)H]PK11195 using 18 kDa translocator protein (TSPO) derived from rat kidney mitochondrial fractions. All analogues showed superior binding affinities for TSPO compared to DPA-713 (5) and DPA-714 (6). Picomolar affinities were observed for this class of TSPO ligands in this assay for the first time, with phenethyl ether 28 showing the greatest affinity (Ki = 0.13 nM). Additionally, all analogues increased pregnenolone biosynthesis (134-331% above baseline) in a rat C6 glioma cell steroidogenesis assay.

    View details for DOI 10.1016/j.ejmech.2015.02.004

    View details for Web of Science ID 000351646100040

  • Could 18F-DPA-714 PET imaging be interesting to use in the early post-stroke period? EJNMMI Research Ribeiro, M., Vercouillie, J., Debiais, S., Cottier, J., Bonnaud, I., Camus, V., Banister, S., Kassiou, M., Arlicot, N., Guilloteau, D. 2014; 4
  • [(18) F]DPA-714: Direct Comparison with [C-11]PK11195 in a Model of Cerebral Ischemia in Rats PLOS ONE Boutin, H., Prenant, C., Maroy, R., Galea, J., Greenhalgh, A. D., Smigova, A., Cawthorne, C., Julyan, P., Wilkinson, S. M., Banister, S. D., Brown, G., Herholz, K., Kassiou, M., Rothwell, N. J. 2013; 8 (2)


    Neuroinflammation is involved in several brain disorders and can be monitored through expression of the translocator protein 18 kDa (TSPO) on activated microglia. In recent years, several new PET radioligands for TSPO have been evaluated in disease models. [(18)F]DPA-714 is a TSPO radiotracer with great promise; however results vary between different experimental models of neuroinflammation. To further examine the potential of [(18)F]DPA-714, it was compared directly to [(11)C]PK11195 in experimental cerebral ischaemia in rats.Under anaesthesia, the middle cerebral artery of adult rats was occluded for 60 min using the filament model. Rats were allowed recovery for 5 to 7 days before one hour dynamic PET scans with [(11)C]PK11195 and/or [(18)F]DPA-714 under anaesthesia.Uptake of [(11)C]PK11195 vs [(18)F]DPA-714 in the ischemic lesion was similar (core/contralateral ratio: 2.84±0.67 vs 2.28±0.34 respectively), but severity of the brain ischemia and hence ligand uptake in the lesion appeared to vary greatly between animals scanned with [(11)C]PK11195 or with [(18)F]DPA-714. To solve this issue of inter-individual variability, we performed a direct comparison of [(11)C]PK11195 and [(18)F]DPA-714 by scanning the same animals sequentially with both tracers within 24 h. In this direct comparison, the core/contralateral ratio (3.35±1.21 vs 4.66±2.50 for [(11)C]PK11195 vs [(18)F]DPA-714 respectively) showed a significantly better signal-to-noise ratio (1.6 (1.3-1.9, 95%CI) fold by linear regression) for [(18)F]DPA-714.In a clinically relevant model of neuroinflammation, uptake for both radiotracers appeared to be similar at first, but a high variability was observed in our model. Therefore, to truly compare tracers in such models, we performed scans with both tracers in the same animals. By doing so, our result demonstrated that [(18)F]DPA-714 displayed a higher signal-to-noise ratio than [(11)C]PK11195. Our results suggest that, with the longer half-life of [(18)F] which facilitates distribution of the tracer across PET centre, [(18)F]DPA-714 is a good alternative for TSPO imaging.

    View details for DOI 10.1371/journal.pone.0056441

    View details for Web of Science ID 000315970300162

    View details for PubMedID 23418569

  • A practical, multigram synthesis of the 2-(2-(4-alkoxyphenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-yl)acetamide (DPA) class of high affinity translocator protein (TSPO) ligands TETRAHEDRON LETTERS Banister, S. D., Wilkinson, S. M., Hanani, R., Reynolds, A. J., Hibbs, D. E., Kassiou, M. 2012; 53 (29): 3780-3783
  • The 2-alkyl-2H-indazole regioisomers of synthetic cannabinoids AB-CHMINACA, AB-FUBINACA, AB-PINACA, and 5F-AB-PINACA are possible manufacturing impurities with cannabimimetic activities FORENSIC TOXICOLOGY Longworth, M., Banister, S. D., Mack, J. B., Glass, M., Connor, M., Kassiou, M. 2016; 34 (2): 286-303
  • A systematic exploration of the effects of flexibility and basicity on sigma (σ) receptor binding in a series of substituted diamines Organic & Biomolecular Chemistry Conroy, T., Manohar, M., Gong, Y., Wilkinson, S., Webster, M., Lieberman, B., Banister, S., Reekie, T., Mach, R. H., Rendina, L., Kassiou, M. 2016

    View details for DOI 10.1039/C6OB00615A

  • The pharmacology of valinate and tert-leucinate synthetic cannabinoids 5F-AMBICA, 5F-AMB, 5F-ADB, AMB-FUBINACA, MDMB-FUBINACA, MDMB-CHMICA, and their analogues ACS CHEMICAL NEUROSCIENCE Banister, S. D., Longworth, M., Kevin, R., Sachdev, S., Santiago, M., Stuart, J., Mack, J. B., Glass, M., McGregor, I. S., Connor, M., Kassiou, M. 2016
  • Pharmacology of Indole and Indazole Synthetic Cannabinoid Designer Drugs AB-FUBINACA, ADB-FUBINACA, AB-PINACA, ADB-PINACA, 5F-AB-PINACA, 5F-ADB-PINACA, ADBICA, and 5F-ADBICA ACS CHEMICAL NEUROSCIENCE Banister, S. D., Moir, M., Stuart, J., Kevin, R. C., Wood, K. E., Longworth, M., Wilkinson, S. M., Beinat, C., Buchanan, A. S., Glass, M., Connor, M., McGregor, I. S., Kassiou, M. 2015; 6 (9): 1546-1559


    Synthetic cannabinoid (SC) designer drugs based on indole and indazole scaffolds and featuring l-valinamide or l-tert-leucinamide side chains are encountered with increasing frequency by forensic researchers and law enforcement agencies and are associated with serious adverse health effects. However, many of these novel SCs are unprecedented in the scientific literature at the time of their discovery, and little is known of their pharmacology. Here, we report the synthesis and pharmacological characterization of AB-FUBINACA, ADB-FUBINACA, AB-PINACA, ADB-PINACA, 5F-AB-PINACA, 5F-ADB-PINACA, ADBICA, 5F-ADBICA, and several analogues. All synthesized SCs acted as high potency agonists of CB1 (EC50 = 0.24-21 nM) and CB2 (EC50 = 0.88-15 nM) receptors in a fluorometric assay of membrane potential, with 5F-ADB-PINACA showing the greatest potency at CB1 receptors. The cannabimimetic activities of AB-FUBINACA and AB-PINACA in vivo were evaluated in rats using biotelemetry. AB-FUBINACA and AB-PINACA dose-dependently induced hypothermia and bradycardia at doses of 0.3-3 mg/kg, and hypothermia was reversed by pretreatment with a CB1 (but not CB2) antagonist, indicating that these SCs are cannabimimetic in vivo, consistent with anecdotal reports of psychoactivity in humans.

    View details for DOI 10.1021/acschemneuro.5b00112

    View details for Web of Science ID 000361505100006

    View details for PubMedID 26134475

  • Effects of Bioisosteric Fluorine in Synthetic Cannabinoid Designer Drugs JWH-018, AM-2201, UR-144, XLR-11, PB-22, 5F-PB-22, APICA, and STS-135 ACS CHEMICAL NEUROSCIENCE Banister, S. D., Stuart, J., Kevin, R. C., Edington, A., Longworth, M., Wilkinson, S. M., Beinat, C., Buchanan, A. S., Hibbs, D. E., Glass, M., Connor, M., McGregor, I. S., Kassiou, M. 2015; 6 (8): 1445-1458
  • Structure-activity relationships of synthetic cannabinoid designer drug RCS-4 and its regioisomers and C4 homologues FORENSIC TOXICOLOGY Banister, S. D., Stuart, J., Conroy, T., Longworth, M., Manohar, M., Beinat, C., Wilkinson, S. M., Kevin, R. C., Hibbs, D. E., Glass, M., Connor, M., McGregor, I. S., Kassiou, M. 2015; 33 (2): 355-366
  • The Therapeutic Potential of alpha(7) Nicotinic Acetylcholine Receptor (alpha(7) nAChR) Agonists for the Treatment of the Cognitive Deficits Associated with Schizophrenia CNS DRUGS Beinat, C., Banister, S. D., Herrera, M., Law, V., Kassiou, M. 2015; 29 (7): 529-542


    Homomeric α7 nicotinic acetylcholine receptors (α7 nAChRs) have implications in the regulation of cognitive processes such as memory and attention, and have shown promise as a therapeutic target for the treatment of the cognitive deficits associated with schizophrenia. Multiple α7 nAChR agonists have entered human trials; however, unfavorable side effects and pharmacokinetic issues have hindered the development of a clinical α7 nAChR agonist. Currently, EVP-6124 is in phase III clinical trials, and several other α7 nAChR agonists (GTS-21 and AQW051) are in earlier stages of development. This review will summarize the recent advances and failures of α7 nAChR agonists in clinical trials for the treatment of the aforementioned pathology.

    View details for DOI 10.1007/s40263-015-0260-0

    View details for Web of Science ID 000360567900002

  • Structure-activity relationship studies of SEN12333 analogues: Determination of the optimal requirements for binding affinities at alpha 7 nAChRs through incorporation of known structural motifs EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY Beinat, C., Reekie, T., Banister, S. D., O'Brien-Brown, J., Xie, T., Olson, T. T., Xiao, Y., Harvey, A., O'Connor, S., Coles, C., Grishin, A., Kolesik, P., Tsanaktsidis, J., Kassiou, M. 2015; 95: 277-301


    Alpha7 nicotinic acetylcholine receptors (nAChRs) have implications in the regulation of cognitive processes such as memory and attention and have been identified as a promising therapeutic target for the treatment of the cognitive deficits associated with schizophrenia and Alzheimer's disease (AD). Structure affinity relationship studies of the previously described α7 agonist SEN12333 (8), have resulted in the identification of compound 45, a potent and selective agonist of the α7 nAChR with enhanced affinity and improved physicochemical properties over the parent compound (SEN12333, 8).

    View details for DOI 10.1016/j.ejmech.2015.03.025

    View details for Web of Science ID 000354139900025

    View details for PubMedID 25827398

  • Recent Advances in the Development of Sigma-1 Receptor Ligands Australian Journal of Chemistry Manohar, M., Banister, S. D., Beinat, C., O'Brien-Brown, J., Kassiou, M. 2015; 68 (4): 600-609

    View details for DOI 10.1071/CH14590

  • Bioisosteric Fluorine in the Clandestine Design of Synthetic Cannabinoids Australian Journal of Chemistry Wilkinson, S. M., Banister, S. D., Kassiou, M. 2015; 68 (1): 4-8

    View details for DOI 10.1071/CH14198

  • Altered proteostasis in aging and heat shock response in C. elegans revealed by analysis of the global and de novo synthesized proteome. Cellular and molecular life sciences : CMLS Liang, V., Ullrich, M., Lam, H., Chew, Y. L., Banister, S., Song, X., Zaw, T., Kassiou, M., Götz, J., Nicholas, H. R. 2014


    Protein misfolding and aggregation as a consequence of impaired protein homeostasis (proteostasis) not only characterizes numerous age-related diseases but also the aging process itself. Functionally related to the aging process are, among others, ribosomal proteins, suggesting an intimate link between proteostasis and aging. We determined by iTRAQ quantitative proteomic analysis in C. elegans how the proteome changes with age and in response to heat shock. Levels of ribosomal proteins and mitochondrial chaperones were decreased in aged animals, supporting the notion that proteostasis is altered during aging. Mitochondrial enzymes of the tricarboxylic acid cycle and the electron transport chain were also reduced, consistent with an age-associated energy impairment. Moreover, we observed an age-associated decline in the heat shock response. In order to determine how protein synthesis is altered in aging and in response to heat shock, we complemented our global analysis by determining the de novo proteome. For that, we established a novel method that enables both the visualization and identification of de novo synthesized proteins, by incorporating the non-canonical methionine analogue, azidohomoalanine (AHA), into the nascent polypeptides, followed by reacting the azide group of AHA by 'click chemistry' with an alkyne-labeled tag. Our analysis of AHA-tagged peptides demonstrated that the decreased abundance of, for example, ribosomal proteins in aged animals is not solely due to degradation but also reflects a relative decrease in their synthesis. Interestingly, although the net rate of protein synthesis is reduced in aged animals, our analyses indicate that the synthesis of certain proteins such as the vitellogenins increases with age.

    View details for DOI 10.1007/s00018-014-1558-7

    View details for PubMedID 24458371

  • Bio-orthogonal labeling as a tool to visualize and identify newly synthesized proteins in Caenorhabditis elegans Nature Protocols Ullrich, M., Liang, V., Chew, Y., Banister, S., Song, X., Zaw, T., Lam, H., Berber, S., Kassiou, M., Nicholas, H. R., Götz, J. 2014; 9: 2237–2255

    View details for DOI 10.1038/nprot.2014.150

  • Effect of maternal immune activation on the kynurenine pathway in preadolescent rat offspring and on MK-801-induced hyperlocomotion in adulthood: Amelioration by COX-2 inhibition Brain, Behavior, and Immunity Zavitsanou, K., Lim, C. K., Purves-Tyson, T., Karl, T., Kassiou, M., Banister, S. D., Guillemin, G. J., Shannon Weickert, C. 2014; 41: 173-181
  • Structure-activity relationships of N-substituted 4-(trifluoromethoxy)benzamidines with affinity for GluN2B-containing NMDA receptors. Bioorganic & medicinal chemistry letters Beinat, C., Banister, S. D., Hoban, J., Tsanaktsidis, J., Metaxas, A., Windhorst, A. D., Kassiou, M. 2014; 24 (3): 828-30


    GluN2B subtype-selective NMDA antagonists represent promising therapeutic targets for the symptomatic treatment of multiple CNS pathologies. A series of N-benzyl substituted benzamidines were synthesised and the benzyl ring was further replaced with various polycyclic moieties. Compounds were evaluated for activity at GluN2B containing NMDA receptors where analogues 9, 12, 16 and 18 were the most potent of the series, replacement of the benzyl ring with polycycles resulted in a complete loss of activity.

    View details for DOI 10.1016/j.bmcl.2013.12.087

    View details for PubMedID 24412068

  • N-substituted 8-aminopentacyclo[,6).0(3,10).0(5,9)]undecanes as sigma receptor ligands with potential neuroprotective effects BIOORGANIC & MEDICINAL CHEMISTRY Banister, S. D., Manoli, M., Barron, M. L., Werry, E. L., Kassiou, M. 2013; 21 (19): 6038-6052


    Several libraries of similarly N-substituted 8-aminopentacyclo[,6).0(3,10).0(5,9)]undecanes (9), N-methyl-8-aminopentacyclo[,6).0(3,10).0(5,9)]undecanes (14), and N-methyl-11-aminopentacyclo[,6).0(3,10).0(5,9)]undecan-8-ones (13) were synthesised and screened against a panel of CNS targets in order to develop structure-affinity relationships for cage-modified trishomocubane σ receptor ligands based on the N-substituted 4-azahexacyclo[,6).0(3,10).0(5,9).0(8,11)]dodecan-3-ol (8) scaffold. In general, compared to the corresponding 4-azahexacyclo[,6).0(3,10).0(5,9).0(8,11)]dodecan-3-ols, compounds of type 9 were potent σ receptor ligands with low levels of subtype selectivity, while the corresponding N-methyl-8-aminopentacyclo[,6).0(3,10).0(5,9)]undecanes showed reduced affinity but greater selectivity for σ2 receptors. The N-methyl-11-aminopentacyclo[,6).0(3,10).0(5,9)]undecan-8-ones demonstrated the poorest σ receptor affinities, suggesting that 4-azahexacyclo[,6).0(3,10).0(5,9).0(8,11)]dodecan-3-ols interact with σ receptors in the bridged hemiaminal form rather than as the non-transannular, aminoketone tautomers. Several compounds of type 8, 9, and 14 were assessed for their ability to inhibit nitric oxide release in vitro, and demonstrated comparable or greater efficacy than 4-phenyl-1-(4-phenylbutyl)piperidine (PPBP), an established neuroprotective σ ligand with NOS inhibitory activity.

    View details for DOI 10.1016/j.bmc.2013.07.045

    View details for Web of Science ID 000324046600012

    View details for PubMedID 23981939

  • A practical synthesis of (1S,4S)-2,5-diazabicyclo[2.2.1]heptane TETRAHEDRON LETTERS Beinat, C., Banister, S. D., McErlean, C. S., Kassiou, M. 2013; 54 (39): 5345-5347
  • The synthesis and pharmacological evaluation of adamantane-derived indoles: cannabimimetic drugs of abuse. ACS chemical neuroscience Banister, S. D., Wilkinson, S. M., Longworth, M., Stuart, J., Apetz, N., English, K., Brooker, L., Goebel, C., Hibbs, D. E., Glass, M., Connor, M., McGregor, I. S., Kassiou, M. 2013; 4 (7): 1081-1092


    Two novel adamantane derivatives, adamantan-1-yl(1-pentyl-1H-indol-3-yl)methanone (AB-001) and N-(adamtan-1-yl)-1-pentyl-1H-indole-3-carboxamide (SDB-001), were recently identified as cannabimimetic indoles of abuse. Conflicting anecdotal reports of the psychoactivity of AB-001 in humans, and a complete dearth of information about the bioactivity of SDB-001, prompted the preparation of AB-001, SDB-001, and several analogues intended to explore preliminary structure-activity relationships within this class. This study sought to elucidate which structural features of AB-001, SDB-001, and their analogues govern the cannabimimetic potency of these chemotypes in vitro and in vivo. All compounds showed similar full agonist profiles at CB1 (EC50 = 16-43 nM) and CB2 (EC50 = 29-216 nM) receptors in vitro using a FLIPR membrane potential assay, with the exception of SDB-002, which demonstrated partial agonist activity at CB2 receptors. The activity of AB-001, AB-002, and SDB-001 in rats was compared to that of Δ(9)-tetrahydrocannabinol (Δ(9)-THC) and cannabimimetic indole JWH-018 using biotelemetry. SDB-001 dose-dependently induced hypothermia and reduced heart rate (maximal dose 10 mg/kg) with potency comparable to that of Δ(9)-tetrahydrocannabinol (Δ(9)-THC, maximal dose 10 mg/kg), and lower than that of JWH-018 (maximal dose 3 mg/kg). Additionally, the changes in body temperature and heart rate affected by SDB-001 are of longer duration than those of Δ(9)-THC or JWH-018, suggesting a different pharmacokinetic profile. In contrast, AB-001, and its homologue, AB-002, did not produce significant hypothermic and bradycardic effects, even at relatively higher doses (up to 30 mg/kg), indicating greatly reduced potency compared to Δ(9)-THC, JWH-018, and SDB-001.

    View details for DOI 10.1021/cn400035r

    View details for PubMedID 23551277

  • The development of radiotracers for imaging sigma (sigma) receptors in the central nervous system (CNS) using positron emission tomography (PET) JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS Banister, S. D., Manoli, M., Kassiou, M. 2013; 56 (3-4): 215-224


    Sigma (σ) receptors are unique mammalian proteins, distributed in the central nervous system and elsewhere, which are increasingly implicated in the pathophysiology of virtually all major central nervous system disorders. The heterogeneous but wide distribution of σ1 in the brain has prompted the development of selective radiotracers for imaging these sites using positron emission tomography (PET). To date, some 50 carbon-11-labelled and fluorine-18-labelled candidate PET radioligands targeting σ receptors have been reported. The historical development of selective σ1 receptor ligands as potential PET imaging agents, as well as the radiochemistry and application of the most recently developed examples, is described herein.

    View details for DOI 10.1002/jlcr.3010

    View details for Web of Science ID 000318174300019

    View details for PubMedID 24285328

  • A sigma(1) receptor pharmacophore derived from a series of N-substituted 4-azahexacyclo[,6).0(3,10).0(5,9).0(8,11)]dodecan-3-ols (AHDs) BIOORGANIC & MEDICINAL CHEMISTRY LETTERS Banister, S. D., Manoli, M., Doddareddy, M. R., Hibbs, D. E., Kassiou, M. 2012; 22 (19): 6053-6058


    A library of N-substituted 4-azahexacyclo[,6).0(3,10).0(5,9).0(8,11)]dodecan-3-ols (AHDs) was synthesized and subjected to competition binding assays at σ(1) and σ(2) receptors, as well as off-target screening of representative members at 44 other common central nervous system (CNS) receptors, transporters, and ion channels. Excluding 3 low affinity analogs, 31 ligands demonstrated nanomolar K(i) values for either σ receptor subtype. Several selective σ(1) and σ(2) ligands were discovered, with selectivities of up to 29.6 times for σ(1) and 52.4 times for σ(2), as well as several high affinity, subtype non-selective ligands. The diversity of structures and σ(1) affinities of the ligands allowed the generation of a σ(1) receptor pharmacophore that will enable the rational design of increasingly selective and potent σ(1) ligands for probing σ(1) receptor function.

    View details for DOI 10.1016/j.bmcl.2012.08.046

    View details for Web of Science ID 000309105200003

    View details for PubMedID 22959245

  • Exploration of ring size in a series of cyclic vicinal diamines with sigma(1) receptor affinity BIOORGANIC & MEDICINAL CHEMISTRY LETTERS Moussa, I. A., Banister, S. D., Manoli, M., Doddareddy, M. R., Cui, J., Mach, R. H., Kassiou, M. 2012; 22 (17): 5493-5497


    Imidazolidine and 1,4-diazepane analogs of N-(2-benzofuranyl)methyl-N'-(4-alkoxybenzyl)piperazines were prepared to explore the effect of ring contraction and expansion on σ receptor affinity and subtype selectivity within a series of cyclic diamines. In vitro receptor binding assays revealed that all cyclic vicinal diamines possessed affinity and selectivity for σ(1) receptors. The imidazolidines possessed nanomolar σ(1) affinities (K(i)=6.45-53.5 nM), and relatively low levels of subtype selectivity (σ(2)/σ(1)=58-237). However, the piperazines and diazepanes achieved picomolar σ(1) interactions, with K(i) ranges of 0.05-10.28 and 0.10-0.194 nM, respectively. Moreover, the piperazines and diazepanes showed excellent discrimination over the σ(2) receptor, with σ(1) selectivities of 143-16140 and 220-11542, respectively.

    View details for DOI 10.1016/j.bmcl.2012.07.026

    View details for Web of Science ID 000308046400027

    View details for PubMedID 22850210

  • 7-Azabicyclo[2.2.1]heptane as a scaffold for the development of selective sigma-2 (sigma(2)) receptor ligands BIOORGANIC & MEDICINAL CHEMISTRY LETTERS Banister, S. D., Rendina, L. M., Kassiou, M. 2012; 22 (12): 4059-4063


    A series of N-substituted 7-azabicyclo[2.2.1]heptanes (12-17 and 22-25) and similarly substituted pyrrolidines (32-36 and 41-44) were synthesized as sterically-reduced, achiral analogs of adamantane- and trishomocubane-derived σ ligands. In vitro competition binding assays against σ receptors revealed that arylalkyl N-substituents conferred selectivity for the σ(2) subtype, while alicyclic or polycarbocyclic substituents imparted high affinity for both subtypes. The σ(2) binding and subtype selectivities of N-arylalkyl-7-azanorbornanes was generally greater than the analogously-substituted pyrrolidines, indicating that steric bulk and conformational restriction around the nitrogen atom are likely important for subtype discrimination.

    View details for DOI 10.1016/j.bmcl.2012.04.077

    View details for Web of Science ID 000304484600041

    View details for PubMedID 22607684

  • Consequences of linker length alteration of the alpha 7 nicotinic acetylcholine receptor (nAChR) agonist, SEN12333 BIOORGANIC & MEDICINAL CHEMISTRY LETTERS Beinat, C., Banister, S. D., van Prehn, S., Doddareddy, M. R., Hibbs, D., Sako, M., Chebib, M., Thao Tran, T., Al-Muhtasib, N., Xiao, Y., Kassiou, M. 2012; 22 (7): 2380-2384


    A series of ligands based on SEN12333, containing either contracted or elongated alkyl chains, were synthesized and evaluated in molecular docking studies against a homology model of the α7 nicotinic acetylcholine receptor (nAChR) subtype. The predicted binding of all ligands was highly similar, with the exception of the analog containing a 5 methylene unit spacer. However, in vitro competition binding assays revealed that the ligands possessed dissimilar binding affinities, with a K(i) range of more than an order of magnitude (K(i)=0.50 to >10 μM), and only SEN12333 itself exhibited functional activity at the α7 nAChR.

    View details for DOI 10.1016/j.bmcl.2012.02.052

    View details for Web of Science ID 000301846100002

    View details for PubMedID 22410083

  • The Therapeutic Potential of Sigma (sigma) Receptors for the Treatment of Central Nervous System Diseases: Evaluation of the Evidence CURRENT PHARMACEUTICAL DESIGN Banister, S. D., Kassiou, M. 2012; 18 (7): 884-901


    Since their proposal in 1976, sigma (σ) receptors have been increasingly implicated in the pathophysiology of virtually all major central nervous system (CNS) disorders, including anxiety, depression, schizophrenia, and drug addiction. Due to their involvement in motor function and higher cognitive function,σ receptors have also been implicated in movement disorders (such as Parkinson's disease) and memory deficits (including Alzheimer's disease). In most cases the precise mechanism(s) linking σ receptors to CNS disease are unknown or yet to be fully elucidated. However, many σ ligands have shown promise in pharmacological studies and animal models of the aforementioned diseases, and some have entered clinical trials. This review will assess the validity of receptors as a target for various CNS diseases based on evidence from animal models of human diseases, preclinical studies in humans, and full clinical trials.

    View details for Web of Science ID 000304444500004

    View details for PubMedID 22288410

  • Synthesis and in vivo evaluation of [F-18]N-(2-benzofuranylmethyl)-N '-[4-(2-fluoroethoxy)benzyl]piperazine, a novel sigma(1) receptor PET imaging agent BIOORGANIC & MEDICINAL CHEMISTRY LETTERS Moussa, I. A., Banister, S. D., Giboureau, N., Meikle, S. R., Kassiou, M. 2011; 21 (22): 6820-6823


    N-(2-Benzofuranylmethyl)-N'-[4-(2-fluoroethoxy)benzyl]piperazine (6, σ(1)K(i)=2.6 nM) was radiolabeled with fluorine-18 to provide a potential σ(1) receptor radioligand for use in positron emission tomography (PET). Radiofluorination of the appropriate tosylate precursor furnished [(18)F]6 with a specific activity of 45 GBq/μmol, in an average radiochemical yield of 18% and greater than 98% radiochemical purity. MicroPET imaging in Papio hamadryas baboon brain revealed [(18)F]6 uptake consistent with σ receptor distribution, and specificity for σ receptors was demonstrated in a haloperidol pre-treated animal. [(18)F]6 possesses suitable properties for PET imaging of σ(1) receptors, and further investigation of this σ(1) receptor tracer is warranted.

    View details for DOI 10.1016/j.bmcl.2011.09.028

    View details for Web of Science ID 000296423700037

    View details for PubMedID 21962578

  • Effects of linker elongation in a series of N-(2-benzofuranylmethyl)-N '-(methoxyphenylalkyl) piperazine sigma(1) receptor ligands BIOORGANIC & MEDICINAL CHEMISTRY LETTERS Moussa, I. A., Banister, S. D., Akladios, F. N., Chua, S. W., Kassiou, M. 2011; 21 (19): 5707-5710


    In our continued exploration of disubstituted piperazine derivatives as sigma (σ) receptor ligands with central nervous system (CNS) activity, a series of N-(2-benzofuranylmethyl)-N'-(methoxyphenylalkyl)piperazines (16-21 and 26-31) were synthesized, anticipating that these ligands would better suit the structural requirements of the current σ(1) pharmacophore. Affinities of these ligands for σ(1) and σ(2) receptors were investigated by means of radioligand binding assays, with the identification of N-(2-benzofuranylmethyl)-N'-[3-(4-methoxyphenyl)propyl]piperazine (29, K(i)=3.1 nM, σ(2)/σ(1)=45) as a selective σ(1) ligand. The σ(1) affinities and subtype selectivities of piperazines 16-21 and 26-31 were generally comparable to the corresponding benzylic analogs. Additionally, the affinities of 16-21 and 26-31 for the 5-HT(2B) receptor were much lower than the relatively nonselective methoxybenzylic analogs 2-4, indicating that elongation of the alkyl tether generally improved selectivity for σ(1) receptors.

    View details for DOI 10.1016/j.bmcl.2011.08.029

    View details for Web of Science ID 000294714400008

    View details for PubMedID 21871797

  • N-Arylalkyl-2-azaadamantanes as cage-expanded polycarbocyclic sigma (sigma) receptor ligands BIOORGANIC & MEDICINAL CHEMISTRY LETTERS Banister, S. D., Yoo, D. T., Chua, S. W., Cui, J., Mach, R. H., Kassiou, M. 2011; 21 (18): 5289-5292


    A series of racemic N-arylalkyl-2-azaadamantan-1-ols (9-15) and the corresponding deoxygenated, achiral N-arylalkyl-2-azaadamantanes (23-29) were synthesized and screened in competition binding assays against a panel of CNS targets. Adamantyl hemiaminals 9-15 displayed generally low affinity for both σ(1) (K(i) values= 294-1950 nM) and σ(2) receptors (K(i) values=201-1020 nM), and negligible affinity for 42 other CNS proteins. Deoxygenation of 9-15 to give the corresponding achiral azaadamantanes 23-29 greatly improved affinity for σ(1) (K(i) values=8.3-239 nM) and σ(2) receptors (K(i) values=34-312 nM).

    View details for DOI 10.1016/j.bmcl.2011.07.028

    View details for Web of Science ID 000294051800033

    View details for PubMedID 21788137

  • Molecular hybridization of 4-azahexacyclo[,6).0(3,10).0(5,9).0(8,11)] dodecane-3-ol with sigma (sigma) receptor ligands modulates off-target activity and subtype selectivity BIOORGANIC & MEDICINAL CHEMISTRY LETTERS Banister, S. D., Moussa, I. A., Jorgensen, W. T., Chua, S. W., Kassiou, M. 2011; 21 (12): 3622-3626


    A series of N-substituted 4-azahexacyclo[,6).0(3,10).0(5,9).0(8,11)]dodecan-3-ols incorporating the respective arylalkyl subunits from several known sigma (σ) receptor ligands were synthesized and evaluated for their affinity against σ receptors and dopamine receptors. The hybrid trishomocubane-derived ligands (4-6) showed good selectivity for σ(1) and σ(2) receptors over multiple dopamine receptors. The molecular hybrid obtained from haloperidol and 4-azahexacyclo[,6).0(3,10).0(5,9).0(8,11)]dodecan-3-ol (4, σ(1)K(i)=27 nM, σ(2)K(i)=55 nM) showed reduced affinity for D(1)-D(5) dopamine receptors when compared to haloperidol itself. The compound with the greatest σ(1) affinity in the series, benzamide 4 (σ(1)K(i)=7.6 nM, σ(2)K(i)=225 nM) showed a complete reversal of the subtype selectivity displayed by the highly σ(2) selective parent benzamide, RHM-2 (3, σ(1)K(i)=10412 nM, σ(2)K(i)=13.3 nM).

    View details for DOI 10.1016/j.bmcl.2011.04.098

    View details for Web of Science ID 000291145900024

    View details for PubMedID 21555222

  • Trishomocubane as a scaffold for the development of selective dopamine transporter (DAT) ligands BIOORGANIC & MEDICINAL CHEMISTRY LETTERS Banister, S. D., Moussa, I. A., Beinat, C., Reynolds, A. J., Schiavini, P., Jorgensen, W. T., Kassiou, M. 2011; 21 (1): 38-41


    In our continued exploration of trishomocubane derivatives with central nervous system (CNS) activity, N-arylalkyl-8-aminopentacyclo[,6).0(3,10).0(5,9)]undecanes (10-13) displaying affinity for the sigma (σ) receptor were also found, in several cases, to interact with the dopamine transporter (DAT). Compound 12 was identified as the first trishomocubane-derived high affinity DAT ligand (K(i) = 1.2 nM), with greater than 8300-fold selectivity over the monoamine transporters NET and SERT, and only low to moderate affinity for σ(1) and σ(2) receptors.

    View details for DOI 10.1016/j.bmcl.2010.11.075

    View details for Web of Science ID 000285544400002

    View details for PubMedID 21146989

  • Insights into Structure-Activity Relationships and CNS Therapeutic Applications of NR2B Selective Antagonists CURRENT MEDICINAL CHEMISTRY Beinat, C., BANISTER, S., Moussa, I., Reynolds, A. J., McErlean, C. S., Kassiou, M. 2010; 17 (34): 4166-4190


    Excessive stimulation of NMDA receptors is involved in various CNS pathologies such as Parkinson's disease, acute and chronic pain and cerebral ischaemia. The use of NMDA antagonists as therapeutic agents has been restricted as a result of unwanted side effects including hallucinations and loss of co-ordination. NR2B subtype selective antagonists have previously shown a therapeutic effect without causing the side effects of broad spectrum NMDA antagonists. Considerable research has since been devoted to the development of orally bioavailable, selective NR2B antagonists and their applications in various neurological diseases. The improved therapeutic index of these compounds is expected to be the result of the subtype selectivity and cellular location of the NR2B receptors within the CNS. This review describes recent advances in the development of NR2B antagonists as well as their therapeutic applications.

    View details for Web of Science ID 000284716400004

    View details for PubMedID 20939817

  • 11-{[2-(3-Fluorophenyl)ethyl](methyl)amino}pentacyclo[,6).0(3,10).0(5,9)]undecan-8-one ACTA CRYSTALLOGRAPHICA SECTION E-STRUCTURE REPORTS ONLINE Banister, S. D., Clegg, J. K., Hanani, R., Kassiou, M. 2010; 66: O2693-U1662


    In the title compound, C(20)H(22)FNO, the distances close to the carbonyl and amine are: N-O = 3.232 (4) Å and N-C = 2.666 (5) Å. The crystal packing is unremarkable.

    View details for DOI 10.1107/S1600536810038523

    View details for Web of Science ID 000282558000156

    View details for PubMedID 21587661

  • Design, Synthesis, and Structure-Affinity Relationships of Regioisomeric N-Benzyl Alkyl Ether Piperazine Derivatives as sigma-1 Receptor Ligands JOURNAL OF MEDICINAL CHEMISTRY Moussa, I. A., Banister, S. D., Beinat, C., Giboureau, N., Reynolds, A. J., Kassiou, M. 2010; 53 (16): 6228-6239


    A series of N-(benzofuran-2-ylmethyl)-N'-benzylpiperazines bearing alkyl or fluoroalkyl aryl ethers were synthesized and evaluated at various central nervous system receptors. Examination of in vitro sigma1 {[3H]+-pentazocine} and sigma2 ([3H]DTG) receptor binding profiles of piperazines 11-13 and 25-36 revealed several highly potent and sigma1 selective ligands, notably, N-(benzofuran-2-ylmethyl)-N'-(4'-methoxybenzyl)piperazine (13, Ki=2.7 nM, sigma2/sigma1=38) and N-(benzofuran-2-ylmethyl)-N'-(4'-(2''-fluoroethoxy)benzyl)piperazine (30, Ki=2.6 nM, sigma2/sigma1=187). Structural features for optimal sigma1 receptor affinity and selectivity over the sigma2 receptor were identified. On the basis of its favorable log D value, 13 was selected as a candidate for the development of a sigma1 receptor positron emission tomography radiotracer. [11C]13 showed high uptake in the brain and other sigma receptor-rich organs of a Papio hamadryas baboon. The in vivo evaluation of [11C]13 indicates that this radiotracer is a suitable candidate for imaging the sigma1 receptor in neurodegenerative processes.

    View details for DOI 10.1021/jm100639f

    View details for Web of Science ID 000280962700028

    View details for PubMedID 20662542

  • Oxo-bridged isomers of aza-trishomocubane sigma (sigma) receptor ligands: Synthesis, in vitro binding, and molecular modeling BIOORGANIC & MEDICINAL CHEMISTRY LETTERS Banister, S. D., Moussa, I. A., Jordan, M. J., Coster, M. J., Kassiou, M. 2010; 20 (1): 145-148


    Isomeric oxo-bridged analogs of aza-trishomocubane sigma (sigma) receptor ligands were synthesized and shown to display a reduced affinity for the sigma receptor. In the case of phenethyl derivative 4, there was a concomitant introduction of high-affinity for the alpha(2C) adrenergic receptor, and moderate affinity for the dopamine transporter. Molecular modeling was undertaken to rationalize these results.

    View details for DOI 10.1016/j.bmcl.2009.11.019

    View details for Web of Science ID 000272935600029

    View details for PubMedID 19954972

  • Fluorine-18 chemistry for PET: A concise introduction Current Radiopharmaceuticals Banister, S., Roeda, D., Dollé, F., Kassiou, M. 2010; 3 (2): 68-80
  • Trishomocubanes: Novel sigma ligands modulate cocaine-induced behavioural effects EUROPEAN JOURNAL OF PHARMACOLOGY Liu, X., Banister, S. D., Christie, M. J., Banati, R., Meikle, S., Coster, M. J., Kassiou, M. 2007; 555 (1): 37-42


    Trishomocubane analogues TC1 (N-(3'-fluorophenyl)ethyl-4-azahexacyclo [,6).0(3,10).0(5,9).0(8,11)]dodecan-3-ol) and TC4 (N-(3'-fluorophenyl)methyl-4-azahexacyclo [,6).0(3,10).0(5,9).0(8,11)]dodecan-3-ol) were evaluated for their modulatory effects on locomotor activity as well as interactions with cocaine-induced responses. TC1 and TC4 have high affinity and moderate to high selectivity for sigma(1) (Ki=10 nM, sigma1/sigma2=0.03) and sigma2 (Ki=20 nM, sigma1/sigma2=7.6) receptor subtypes respectively. Both compounds have negligible affinity for the dopamine (DAT), serotonin (SERT), and norepinephrine (NET) transporters. In behavioural studies, TC1 produced a dose-related inhibition in spontaneous locomotor activity measured in a Digiscan apparatus. TC1 attenuated the stimulatory locomotor effect of 20 mg/kg cocaine with a half-maximal depressant activity (ID50) of 38.6 mg/kg. TC1 (dose range of 25 to 100 mg/kg) also partially substituted for the effect of cocaine (10 mg/kg) in a discriminative stimulus task, involving the trained discrimination between cocaine and saline using a two-lever choice method. Following a dose of 50 mg/kg TC1, a maximum of 31% substitution was reached. The response rate was reduced to 56% of vehicle control following a TC1 dose of 100 mg/kg. These behavioural effects suggest that TC1 can act as an antagonist via the sigma1 receptor. In contrast to TC1, TC4 produced a stimulant effect in locomotor activity with the ED50 estimated at 0.94 mg/kg. In addition, TC4 failed to inhibit cocaine-induced stimulation; neither did it substitute for the discriminative stimulus effects of cocaine. TC4 thus appears to interact predominantly with the sigma2 receptor subtype (sigma1/sigma2=7.6) which may result in dopamine stimulation independent of the effects of cocaine. The differential effect of TC1 and TC4 warrants further study of the mechanism of these actions. Present data also suggests a potential role for trishomocubane analogues in developing medication or research tools for cocaine addiction.

    View details for DOI 10.1016/j.ejphar.2006.10.020

    View details for Web of Science ID 000244008500006

    View details for PubMedID 17113074

  • (1R,2S,3R,6S,7R,8S)-Tricyclo[,7)]-undeca-4,9-diene-3,6-diol ACTA CRYSTALLOGRAPHICA SECTION E-STRUCTURE REPORTS ONLINE Banister, S. D., Clegg, J. K., Coster, M. J., Jolliffe, K. A., Kassiou, M. 2007; 63: O92-O93