Professor Potter studied chemistry as an Open Exhibitioner at Oxford University, graduating with first class honours and winning the Part II Thesis prize in Organic Chemistry. He completed his DPhil at Oxford in Bioorganic/Biological Chemistry as a Graduate Scholar and later Junior Research Fellow, working on the stereochemistry of enzyme-catalysed phosphoryl transfer reactions, developing the now textbook [16O,17O,18O] oxygen chiral phosphate ester approach that he applied to kinase, phosphatase and mutase enzyme mechanisms. After postdocs at Oxford and at the Max-Planck-Institute for Experimentelle Medizin in Goettingen, Germany, as Royal Society European Exchange Fellow and later Wissenschaftlicher Mitarbeiter der Max-Planck Gesellschaft, he became Lecturer in Biological Chemistry at Leicester University and won a Lister Institute of Preventive Medicine Fellowship. In 1990 he moved to the chair of Medicinal Chemistry at the University of Bath, as Lister Institute Research Professor where he holds the Established Chair in the Department of Pharmacy & Pharmacology, as Head of the Medicinal Chemistry Section.
Fields of research activity are at the interface between Chemistry & Biology and Chemistry & Medicine ie Medicinal & Biological Chemistry, Chemical Biology, Mechanistic Enzymology, Signal Transduction Chemistry, Anticancer Drug Design & Discovery and Translational & Molecular Medicine. [See Cover Gallery] Particular interests are in the chemistry of cellular signalling, using carbohydrate, nucleotide and cyclitol chemistry to explore the chemical biology and pharmacology of second messengers that mobilise intracellular calcium, such as myo-inositol 1,4,5-trisphosphate (IP3) and the nucleotides cyclic ADP ribose (cADPR) and nicotinic acid adenine dinucleotide phosphate (NAADP). The research group is highly international [See Group Photo Gallery] and has developed numerous synthetic structurally-modified ligands in all classes that have found widespread uses as chemical biological tools, some with proven activity in disease models. In Medicinal Chemistry, the group has pioneered inter alia, a novel pharmacophore in anti-cancer drug design and, unusually within an academic setting, has brought several compounds from novel therapeutic concept to multiple Phase I and II human clinical trials (19 to date), with other drug candidates in pre-clinical development. Evidence of efficacy has been notably in oncology directed against the novel target steroid sulfatase and in women’s health. Non-steroidal cancer drugs designed at Bath are currently in Phase II clinical trials in metastatic breast cancer, endometrial cancer & prostate cancer and the steroid derivative PGL2001 is currently in Phase II trials for endometriosis.
He co-founded the university spin out company Sterix Ltd where he was Director of Medicinal Chemistry and subsequently Chief Scientific Officer and that was acquired by major pharma; he is a Fellow of the Royal Society of Chemistry, the Society of Biology, the Institute of Directors and the Royal Society of Arts and has published over 500 research articles [see eg http://www.researcherid.com/rid/A-1845-2012]with ca 400 formally granted patents to date worldwide from many diverse families, including 45 USPs, 25 EPs and 10 JPs. He was elected to Membership of the Lister Institute of Preventive Medicine in 1995. He served on the BBSRC Intracellular Signalling Programme Committee (1992–1996) and the EPSRC Synthetic and Biological Chemistry College (1995–1997) and is a member of the Wellcome Trust Peer Review College (2012-2015). He is a member of the Biochemical Society, the American Association for Cancer Research and the American Chemical Society and was a committee member of the Society for Medicines Research (2002-2006). He was a member of the HEFCE Pharmacy/ Pharmacology Panel for the RAE2001 and RAE2008 exercises and the Research Excellence Framework (REF) Expert Group Panel 2009 and was a member of the Molecules, Genes & Cells Funding Panel of the Wellcome Trust (2006-2011). He is on the editorial boards of the ACS Journal of Medicinal Chemistry (2009-2015), AACR Molecular Cancer Therapeutics (2009-2015), Messenger (2012-) and Future Medicinal Chemistry (2008-), and is a member of the International Advisory Board of ChemMedChem (2014-2017). He has served on the boards of the Biochemical Journal, Carbohydrate Research, Current Organic Synthesis, Drug Design & Discovery and is currently Associate Editor of the Journal of Steroid Biochemistry & Molecular Biology (2009-15) and Editor of the Biochemical Journal's BJChemBio (2009-2016). He received a DSc from Oxford in 1993 and is Visiting Professor of Medicinal Chemistry at Oxford University. He was named in the “H-index ranking of living chemists” listing (current h-index 58).
Professor Potter was the recipient of the Royal Society of Chemistry UCB-Celltech Industrially Sponsored Award and Medal for Chemical Biology for 2007, the Royal Society of Chemistry George and Christine Sosnovsky Award & Medal for Cancer Medicinal Chemistry for 2007/8 with an RSC Endowed Lectureship, the Royal Society of Chemistry Biological & Medicinal Chemistry Sector’s Malcolm Campbell Memorial Prize & Medal for 2009, the GlaxoSmithKline International Achievement Award for 2009 and the Royal Society of Chemistry Interdisciplinary Prize & Medal for 2010 with an RSC Endowed Lectureship. He won the category “Investigator of the Year” at the 2012 European Life Science Awards. He was awarded the RSC-BCMS Endowed Lectureship in Medicinal Chemistry for 2015/16. He was elected to Fellowship of the Academy of Medical Sciences in 2008 and in 2009 to Membership of the Academia Europaea.
X-ray crystal structures of synthetic ligands from the group determined in complex with their target proteins:
Research is centred around four main areas of Chemical Biology and
Synthetic Medicinal and Biological Chemistry:
Inositol phosphate-mediated cellular signalling:
Cyclic ADP-ribose - a new second messenger:
The cyclic nucleotide cyclic adenosine 5'-diphosphate ribose, formed via enzyme-mediated cyclisation of NAD+ is a recently identified Ca2+-releasing second messenger, that works independently of inositol 1,4,5-trisphosphate. A combination of techniques from total synthesis to chemo-enzymatic methods is being used to synthesize novel mimics, agonists, antagonists and ADP-ribosyl cyclase inhibitors related to this new signalling pathway for chemical biological intervention in multiple systems, but especially in T cells, working in collaboration with colleagues at the University of Hamburg and Oxford University. Recent work has defined SAR parameters for an invertebrate cADPR receptor and also focused upon a total synthesis of a stable active macrocyclic template. [see cover design] Selected ligands are co-crystallised with suitable binding proteins such as ADP-ribosyl cyclases and CD38 for X-ray crystallography, structure-based design and elucidation of enzyme mechanisms; examples shown are a CD38-cIDPR complex and a complex of Aplysia californica ADP-ribosyl cyclase with 2-fluoro-NAD+. Recent work demonstrates the continuing unusual effects of targeted chemical modification in an active but stable template that we have pioneered, including replacement of the pyrophosphate moiety with retention of biological activity. The use of our stable cIDPR template facilitates structure-based design using ligands co-crystallised with CD38 ectoenzyme for improvement of activity.
ADP-ribose, a new second messenger & TRPM2:
Adenosine 5'-diphosphoribose controls opening of the ligand-gated cation channel TRPM2, expressed mainly in the immune system and in the brain, by binding to the cytoplasmic C-terminal NudT9H domain. Small molecules are being designed, working also in collaboration with colleagues at Hamburg University, to interfere with the ADPR-TRPM2 interaction, that will elucidate structure-activity relationships and may be of potential therapeutic application. The first structure-activity relationship for the TRPM2 ion channel has recently been developed, with nucleotide agonists and antagonists designed
This project is supported by a Wellcome Trust Project Grant.
NAADP - a new second messenger:
The NAD+ derivative, nicotinic acid adenine dinucleotide phosphate (NAADP) is a Ca2+-releasing second messenger that works independently of inositol 1,4,5-triphosphate and cADPR. NAADP represents a newly identified messenger in T cells involved in antigen receptor-mediated calcium signalling.
A combination of techniques from total synthesis to chemo-enzymatic methods is being used to design and synthesize novel mimics, antagonists and chemical biological tools to probe this new signalling pathway, with colleagues at Hamburg and Oxford. We have shown in recent work that calcium signalling controlled by nicotinic acid adenine dinucleotide phosphate is relevant for the pathogenic potential of autoimmune effector T cells. Specific inhibition of the NAADP signalling pathway is emerging as a way to specifically and effectively modulate T-cell activation and has particular potential in the therapy of autoimmune diseases such as multiple sclerosis and the first small molecules can be designed to illuminate such potential.
Anticancer drug design, discovery & translational medicine:
Steroid Sulfatase Inhibitors:
Many tumours are 17β-estradiol-dependent and hydrolysis of the conjugate estrone 3-O-sulfate by STS is a source of tumour estrogen, especially in situ. We designed the first highly potent active-site-directed time- and concentration-dependent irreversible inhibitors of STS. Enzyme sulfamoylation and inactivation occurs most likely via a liberated highly electrophilic sulfonylamine species. Recent work has consolidated the SAR of this new drug class. Our early agent has reached multiple phase II clinical trials for a hormone replacement therapy indication. The virtual absence of hepatic estrogenicity and the production of clotting factors may reduce the risk of adverse events normally associated with HRT. Estrogen sulfamates are a new type of estrogen which not only inhibit STS, but are sequestered by carbonic anhydrase (CAII) in erythrocytes and transit the liver without undergoing first-pass inactivation. They possess many attractive properties for drug design, being orally active with excellent bioavailability and pharmacokinetics and bound as their anion by CAII in red blood cells. We have solved the X-ray crystal structures of numerous sulfamate drug : CAII complexes at Bath.
The STS inhibitor PGL2001, designed at Bath, has the potential to be the first of a new class of drug for benign gynaecological conditions and has entered Phase II clinical trial against endometriosis since 2012. Our non-steroidal drug STX64 [6-oxo-6,7,8,9,10,11-hexahydrocyclo-hepta[c] benzopyran-3-yl sulfamate], formally named Irosustat, a potent tricylic sulfamate derivative, was selected by CRUK for a “first-in-class” clinical trial of a STS inhibitor in women with advanced breast cancer and showed evidence of stable disease. Phase II trials in patients are now complete in endometrial and breast cancer, and further US trials have taken place in men in androgen-dependent prostate cancer. The drug class also has potential in ovarian cancer and in other hormone dependent pathologies. Irosustat is currently in two breast cancer clinical trials, supported by CRUK.
Aromatase inhibitors in current clinical use block the biosynthesis of steroidal estrogens by inhibiting aromatisation of the A-ring of androgenic precursors. We recently defined a novel class of picomolar-potent aromatase inhibitor based upon a biphenyl template linked to a triazole moiety. Using the topical idea of polypharmacology, blockade of aromatase and sulfatase enzymes should provide a more effective endocrine therapy. We proposed the concept of a dual aromatase-sulfatase inhibitor (DASI) in one molecule and introduced our aryl sulfamate pharmacophore into three clinically established aromatase inhibitors. Advanced dual inhibitors have great potential, being exquisitely potent with dual IC50s of eg 130pM and 18pM. The movie below shows examples of typical very potent DASIs and the docking of a highly potent biphenyl-based dual inhibitor, designed at Bath, into the active site of human CAII, based upon our X-ray crystal structure of the inhibitor-CAII complex.
A steroidal antitumour/antiangiogenesis microtubule disruptor of clinical
potential, using our new pharmacophore for dual structural augmentation and
protection against metabolic conjugation, is in formal preclinical
development for oncology. STX 140, suitable for targeting taxane
resistant tumours, is active against multi-drug and taxane-resistant
tumours and those expressing the drug efflux pump P-glycoprotein. It surprisingly binds to carbonic anhydrase via
the non-aryl sulfamate and we discovered by protein
crystallography a second STX140 binding site on the enzyme. The pharmacophoric
elements of STX140 are being translated into highly potent chimeric non-steroidal microtubule disruptors
with very attractive pharmaceutical properties and activities
and this template has considerable potential more widely as a steroidomimetic template that
is being actively pursued, for example in a recent dihydroisoquinoline
A steroidal antitumour/antiangiogenesis microtubule disruptor of clinical potential, using our new pharmacophore for dual structural augmentation and protection against metabolic conjugation, is in formal preclinical development for oncology. STX 140, suitable for targeting taxane resistant tumours, is active against multi-drug and taxane-resistant tumours and those expressing the drug efflux pump P-glycoprotein. It surprisingly binds to carbonic anhydrase via the non-aryl sulfamate and we discovered by protein crystallography a second STX140 binding site on the enzyme. The pharmacophoric elements of STX140 are being translated into highly potent chimeric non-steroidal microtubule disruptors with very attractive pharmaceutical properties and activities and this template has considerable potential more widely as a steroidomimetic template that is being actively pursued, for example in a recent dihydroisoquinoline series.
Dehydrogenase Inhibition: 17β-Hydroxysteroid dehydrogenases types 1&3(17β-HSDs) catalyse the interconversion between the oxidised and reduced forms of androgens and estrogens at the 17-position, are expressed in malignant cells and possess unexploited therapeutic potential as targets for anticancer drug design. Potent and selective low nanomolar inhibitory druglike candidates are being synthesised and evaluated using both enzymes and via protein crystallography. Small molecule synthetic drug candidates directed at both 17β-HSD types 1 & 3 have successfully been demonstrated to exhibit in vivo activity in tumour models.
Efforts directed at novel approaches to diabetes and metabolic syndrome are being pursued by inhibition of the target enzyme 11β-hydroxysteroid dehydrogenase. Low nanomolar active inhibitors have been designed, synthesized and evaluated in whole cell assays using human 11β-HSD transfected HEK293 cells and by protein crystallography. Typical potent examples are shown below:
Research in these areas has been supported by CRUK and through industry.
Novel antagonists at the nicotinic acetylcholine receptor:
Research (with Dr I S Blagbrough) is centred around the exploitation of a very potent natural product alkaloid lead compound, methyllycaconitine, the value of which was apparent in Roman times, for the design and synthesis of novel small molecule antagonists at the nicotinic acetylcholine receptor. The project employs a range of synthetic techniques to prepare novel polycycles, which are evaluated for nicotinic antagonist potency in the Department of Biology and Biochemistry (with Professor S J Wonnacott). Potent small molecule mimics have been designed that have potential for use in neurodegenerative diseases and as safer insecticides.
In vivo and in vitro properties of STX2484: a non-steroidal anticancer compound active in taxane-resistant cells
C Stengel, S P Newman, S K Chander, F L Jourdan M P Leese, E Ferrandis, S Regis-Lydi, B V L Potter, M J Reed, A Purohit, and P A Foster Brit J Cancer (2014) 111, 300-308.
Optimisation of Tetrahydroisoquinoline based Chimeric Microtubule Disruptors
W Dohle, F L Jourdan, C J Chapman, M P Leese, E Hamel, E Ferrandis and B V L Potter ChemMedChem (2014) 9, 1783 – 1793.
H Wang, H Y Godage, A M Riley, J D Weaver, S B Shears and B V L Potter Chemistry & Biology (2014) 21, 689–699.
A M Riley, S Windhorst, Hong-Yin Lin and B V L Potter ChemBioChem (2014) 15, 57–67.
Tetrahydroisoquinoline based steroid-mimetic and chimeric microtubule disruptors
M P Leese, F Jourdan, M R Major, W Dohle, R Bai, E Hamel, Eric Ferrandis, A Fiore P Kaspryzk, and B V L Potter ChemMedChem (2014) 9, 85-108. [VIP Article with front cover design].
M P Thomas and B V L Potter FEBS J (2014) 281, 14-33.
J M Swarbrick, R Graeff, C Garnham, M P Thomas, A Galione and B V L Potter Chem Comm (2014) 50, 2458-2461.
Synthesis, antitubulin and anti-proliferative SAR of C3/C1 substituted N-benzyl-7-methoxy-6-O-sulfamoyl-1,2,3,4-tetrahydroisoquinolines
W Dohle, M P Leese, F Jourdan, M R Major, R Bai, E Hamel, Eric Ferrandis, A Fiore, S P Newman, A Purohit and B V L Potter ChemMedChem (2014) 9, 350 – 370.
N Kudukkil Pulloor, S Nair, A D Kostic, P Bist, J D Weaver, A M Riley, R Tyagi, P D Uchil, John D York, S H Snyder, A García-Sastre, B V L Potter, R Lin, S B Shears, R J Xavier and M N Krishnan PLOS Pathog (2014) 10, e1003981, 1-16.
M P Leese F Jourdan, M R Major, W Dohle, MP Thomas, E Hamel, E Ferrandis, M Mahon, S P Newman, A Purohit and B V L Potter ChemMedChem (2014) 9, 798 – 812 [VIP Article].
C Moreau, T Kirchberger, JM Swarbrick, S J Bartlett, Y Timur, R Fliegert, T Yorgan A Bauche, A Harneit, A H Guse and B V L Potter J Med Chem (2013) 56, 10079-102.
288(22), 16017-16030 [JBC Paper of the Week].
M P Thomas and B V L Potter J Steroid Biochem Mol Biol (2013) 137, 27-49.
L W L Woo, P M Wood, C Bubert, M P Thomas, A Purohit, and B V L Potter ChemMedChem (2013) 8, 779 – 799.
STX2171, a 17b-hydroxysteroid dehydrogenase Type 3 (17b-HSD3) inhibitor, is efficacious in vivo in a novel hormone-dependent prostate cancer model
J M Day, PA Foster, H J Tutill, F. Schmidlin, J D Hargrave, N Vicker, B V L Potter, M J Reed and A Purohit Endocrine-Related Cancer (2013) 20, 563-64.
N Veiga, Torres, I Macho, K Gómez, H Y Godage, A M Riley, B V L Potter, G González and Kremer Dalton Trans (2013) 42, 6021-6032.
S ALi Khan, A M Rossi, A M Riley, B V L Potter and C W Taylor Biochem J (2013) 451, 177-184.
H Y Godage, A M Riley, T J Woodman. M P Thomas, M F Mahon & B V L Potter J Org Chem (2013) 78, 2275−2288 [Featured Article].
H Saleem, S C Tovey, A M.Riley, B V L Potter and C WTaylor PLOS ONE (2013) 8, e58027 1-12.
H Saleem, S C Tovey, T Rahman, A M Riley, B V L Potter and C W Taylor PLOS ONE (2013) 8, e54877, 1-14.
A M Riley, H Wang, J D Weaver, S B Shears and B V L Potter Chem Comm (2012) 48, 11261-11368 [with journal front cover feature]
Adamantyl carboxamides and acetamides as potent 11β-hydroxysteroid dehydrogenase type 1 inhibitors
X Su, H A Halem, M P Thomas, C Moutrille, M D Culler, N Vicker and B V L Potter Bioorg Med Chem (2012) 20,6394-6402.
T Grint, A M Riley, S J Mills, B V L Potter and S T Safrany Messenger (2012) 1, 160-166.
S J Mills, T Luyten, C Erneux, J B Parys and B V L Potter Messenger (2012) 1, 167-181.
Synthesis and evaluation of thiadiazole derivatives as selective 11β-hydroxysteroid dehydrogenase type 1 inhibitors
F Pradaux-Caggiano, X Su, N Vicker, M P Thomas, D Smithen, H A Halem, M D Culler and B V L Potter MedChemComm (2012) 3, 1117-1124.
B L Turner, A W Cheeseman, H Y Godage, A M. Riley and B V L Potter ACS Environmental Sci Tech (2012) 46, 4994-5002.
See also: Response to ‘Comment on “Determination of neo- and d-chiro-inositol hexakisphosphate in soils by solution 31P NMR spectroscopy”’
B L Turner, A W Cheesman, H Y Godage, A M. Riley, B VL Potter Environmental Sci Tech (2012) 46, 11480-11481
S J Mills, C Persson, G Cozier, M P Thomas, L Trésaugues, C Erneux, A M Riley, P Nordlund and B V L Potter ACS Chem Biol (2012) 7, 822−828.
Synthesis and evaluation of A-ring modified analogues of estrone-3-O-sulfamate as potent steroid sulfatase inhibitors.
L W L Woo, B Leblond, A Purohit and B V L Potter Bioorg Med Chem (2012) 20, 2506–2519.
C Moreau, T Kirchberger, M P Thomas, K Weber, A H Guse and B V L Potter J Med Chem (2012) 55, 1478-1489.
J M Swarbrick and B V L Potter J Org Chem (2012) 77, 4191-4197 [Featured Article, with journal front cover design].
K M Sureshan, A M Riley, S C Tovey, C W Taylor and B V L Potter J Med Chem (2012) 55, 1706-1720.
M P Leese, W Dohle, F Jourdan, M Kimberley, R Bai, E Hamel, E Ferrandis and B V L Potter ACS MedChemLett (2012) 3, 5-9.
L W L Woo, D Ganeshapillai,M P Thomas,O B Sutcliffe, B Malini, M F Mahon, A Purohit and B V L Potter ChemMedChem (2011) 6, 2109-2034
Adamantyl ethanone pyridyl derivatives:
potent and selective inhibitors of human cellular 11β-hydroxysteroid
dehydrogenase type 1.
relationships of C-17-substituted estratriene-3-O-sulfamates as anticancer
Aromatase and Dual Aromatase-Steroid
Sulfatase Inhibitors from the Letrozole and Vorozole Templates.
Discovery of adamantyl
heterocyclic ketones as potent human cellular 11β-hydroxysteroid
dehydrogenase type 1 inhbitors.
of cyclic adenosine 5'-diphosphate ribose analogues: a C2' endo/syn “southern” ribose conformation underlies activity at
the sea urchin cADPR receptor.
Development of Steroid Sulfatase Inhibitors.
L W L Woo, A Purohit and B V L Potter, Mol Cell Endocrinol (2011) 340, 175-185.
Crystal Structures of 11β-Hydroxysteroid
Dehydrogenase Type 1 and Their Use in Drug Discovery.
Steroid Sulfatase: A
Pivotal Player in Estrogen Synthesis and
Selective Determinants of IP3
and Adenophostin A Interactions with Type 1
Bicyclic derivatives of the potent Dual Aromatase-Steroid
Sulfatase Inhibitor 2-bromo-4-(((4-cyanophenyl)(4H-1,2,4-triazol-4-yl)amino)methyl)phenyl
sulfamate: Synthesis, SAR, Crystal Structure, in
vitro and in vivo Activities.
mediated Ca2+ signaling in effector
cells regulates autoimmunity of the nervous system.
of adamantyl ethanone
derivatives as potent 11β-hydroxysteroid
dehydrogenase type 1 inhibitors.
Structures of four human carbonic anhydrase
II/inhibitor complexes reveal a second binding site for steroidal and
Binding of IP3
and Adenophostin A to the N-terminal Region of the
IP3 Receptor: Thermodynamic Analysis Using Fluorescence
Polarization with a Novel IP3 Receptor Ligand.
Chimeric Microtubule Disruptors.
and Anti-proliferative SAR of Analogues of
Highly potent first examples of dual
aromatase-steroid sulfatase inhibitors based on a biphenyl template.
A novel inhibitor of the PI3K/Akt pathway based on the structure of inositol 1,3,4,5,6 pentakisphosphate.
Class III beta-tubulin expression and in
vitro resistance to microtubule targeting agents.
Basis for Enzymatic Evolution from a Dedicated ADP-ribosyl
cyclase to a Multiple Functional NAD Hydrolase.
The behaviour of inositol 1,3,4,5,6-pentakisphosphate in the presence of the major
biological metal cations.
Determination of the absolute configuration
of aromatase and dual aromatase-sulfatase inhibitors by vibrational and
electronic circular dichroism spectral analysis.
partial agonists reveal key steps in IP3 receptor activation.
8-Bromo-cyclic inosine diphosphoribose: towards a selective cyclic ADP-ribose
mediated Ca2+ signaling via type 1
ryanodine receptor in T cells revealed by a synthetic NAADP antagonist.
The development of steroid sulfatase inhibitors
for hormone-dependent cancer therapy.
Discovery of Adamantyl
Amides as Novel Selective Inhibitors of Human 11β-Hydroxysteroid
Dehydrogenase Type 1.
The Design of Novel 17β-Hydroxysteroid
Dehydrogenase Type 3 Inhibitors.
Development of hormone-dependent prostate
cancer models for the evaluation of inhibitors of 17β-hydroxysteroid
dehydrogenase Type 3.
BCRP expression does not result in
resistance to STX140 in vivo, despite the increased expression of BCRP in
A2780 cells in vitro after long-term STX140 exposure.
2-Methoxyoestradiol-3,17-O,O-bis-sulphamate and 2-deoxy-D-glucose in combination: a potential treatment for breast and prostate cancer. S L C Tagg, P A Foster, M P Leese, B V L Potter, M J Reed, A Purohit and S P Newman, Brit J Cancer (2008) 99, 1842-1848.
Effects of C-17 Heterocyclic substituents
on the anticancer activity of 2-ethylestra 1,3,5(10)-triene-3-O-sulfamates:
Synthesis, in vitro evaluation and computational modelling.
Synthesis of aromatase inhibitors and dual
aromatase-sulfatase inhibitors by linking an arylsulfamate
motif to 4-(4H-1,2,4-triazol-4-ylamino)benzonitrile:
SAR, crystal structures, in vitro and in vivo activities.
The in vivo properties of STX243: a potent
A new therapeutic strategy against
hormone-dependent breast cancer: The preclinical development of a dual
aromatase and sulfatase inhibitor.
The use of steroid sulfatase inhibitors as
a novel therapeutic strategy against hormone dependent endometrial cancer.
Steroid sulfatase inhibitors and endometrial cancer.
Efficacy of three potent steroid sulfatase
inhibitors: Pre-clinical investigations for their use in the treatment of
hormone-dependent breast cancer.
2-MeOE2bisMATE and 2-EtE2bisMATE induce
cell cycle arrest and apoptosis in breast cancer xenografts as shown by a
novel ex vivo technique.
Design and synthesis of 4”,6”-unsaturated
cyclic ADP-carbocyclic ribose, a Ca2+-mobilizing agent selectively active in
inhibitors as a target for the topical treatment of skin disorders.
Benzene Polyphosphates as tools for cell signaling: interaction with the PH domain of protein
kinase Ba and inhibition of inositol 1,4,5-trisphosphate
Chiral Aromatase and Dual Aromatase-Steroid
Sulfatase Inhibitors from the Letrozole Template:
Synthesis, Absolute Configuration and In Vitro Activity.
Anti-cancer steroid sulfatase inhibitors:
synthesis, in vitro and in vivo activities, molecular modelling and protein
crystallography of a potent fluorinated second-generation agent.
Inhibition of steroid sulphatase
activity in endometriotic implants by 667COUMATE: a
potential new therapy.
STX140 is efficacious in vitro and in vivo
in taxane resistant breast carcinoma cells.
Direct Evidence for ArO-S
Bond Cleavage upon Inactivation of Pseudomonas aeruginosa Arylsulfatase by
Base-Modified Analogs of Adenophostin
A as High-Affinity Agonists of the D-myo-Inositol
Trisphosphate Receptor: In Vitro Evaluation and Molecular Modeling.
Chemoenzymatic synthesis of 7-deaza cyclic adenosine
5'-diphosphate ribose analogues, membrane permeant modulators of
intracellular calcium release.
17ß-Hydroxysteroid dehydrogenase type 1 and
not type 12 is a target for endocrine therapy of hormone-dependent breast
Cyclic Adenosine 5'-Diphosphate Ribose Derivatives: Importance of a 2'
Hydroxyl Motif for the Antagonistic Activity of 8-Substituted cADPR Derivatives.
Structure-Activity Relationships of C-17 Cyanated Estratrienes as
Inhibitors of 11ß-Hydroxysteroid
Dehydrogenase Type 1.
Novel Non-steroidal Aromatase Inhibitors
Based On a Biphenyl Scaffold: synthesis, in vitro SAR and molecular
Novel Inhibitors of 17ß Hydroxysteroid
Dehydrogenase Type 1: Templates for Design.
The therapeutic potential of a series of
orally bioavailable anti-angiogenic microtubule disruptors as therapy for
hormone-independent prostate and breast cancers.
Dual aromatase-sulfatase inhibitors based
on the anastrozole template: synthesis, in vitro
SAR, molecular modelling and in vivo activity.
Catalysis associated conformational changes
revealed by human CD38 complexed with a non-hydrolyzable
2-alkyestra-1,3,5(10)-trien-3-ol derivatives: synthesis, in vitro and in vivo
Dual aromatase-steroid sulfatase
inositol phospholipid headgroup surrogate
crystallised in the PH domain of protein kinase Ba.
dinucleotide unmasks the NAD+ glycohydrolase activity of Aplysia
Californica adenosine 5'-diphosphate-ribosyl cyclase.
novel inositol polyphosphate surrogate, inhibits the activity of two inositide 5-phosphatases and modulates Ca2+
responses in rat hepatocytes.
Rapid and efficient routes to
phosphatidylinositol 3,4,5-trisphosphates via myo-inositol
bis-sulfamates, multi-targeted anti-tumor agents: Synthesis, in vitro SAR, protein
crystallography and in vivo activity.
3-Hydroxybenzene 1,2,4-trisphosphate, a
novel second messenger mimic and unusual substrate for type-I myo-inositol 1,4,5-trisphosphate 5-phosphatase: Synthesis
Cellular effects and metabolic stability of
N1-cyclic inosine diphosphoribose and its
A Systematic study of C-glucoside
trisphosphates as myo-inositol trisphosphate
receptor ligands. Synthesis of -C-glucoside trisphosphates based on the
conformational restriction strategy.
Design and synthesis of
5'-deoxy-5'-phenyladenophostin A, a highly potent IP3 receptor ligand.
Focused libraries of 16 substituted estrone derivatives and modified E-ring steroids:
Inhibitors of 17 -hydroxysteroid dehydrogenase type
Guanophostin A: Synthesis and evaluation of a high affinity
agonist of the D-myo-inositol 1,4,5 trisphosphate
Regioselective hydrolysis of myo-inositol
1,3,5-orthobenzoate via a 1,2-Bridged 2-phenyl-1',3'-dioxolan-2'-ylium ion
provides a rapid route to the anticancer agent Ins(1,3,4,5,6)P5.
Structural determinants for N1/N7
cyclization of nicotinamide hypoxanthine 5'-dinucleotide (NHD+) derivatives
by ADP-ribosyl cyclase from Aplysia
Californica: Ca2+-mobilizing activity of
8-substituted cyclic inosine 5'-diphosphoribose analogues in T-lymphocytes.
Cell-permeant small-molecule modulators of
NAADP-mediated Ca2+ release.
Rapid microwave-assisted reductive amination of ketones with anilines.
as an analogue of myo-inositol
1,3,4,5,6-pentakisphosphate: chemical synthesis, physicochemistry
and biological applications.
In vivo efficacy of STX213, a second
generation steroid sulfatase inhibitor for hormone-dependent breast cancer
Phase I study of STX64 (667 Coumate) in breast cancer patients: the first study of a
steroid sulphatase inhibitor.
On the contribution of stereochemistry to
ITPK1 specificity: Ins(1,4,5,6)P4 is not a physiologic substrate.
of myo-inositol 1,3,5-orthobenzoate gives rapid
access to precursors for second messenger analogues.
Modification of estrone
at the 6, 16, 17 positions: Novel potent inhibitors of 17 -hydroxysteroid dehydrogenase type 1.
Unusual entry to the novel
8-halo-N1-ribosyl hypoxanthine system by degradation of a cyclic adenosine-5'-diphosphate
Steroid sulfatase: Molecular biology,
regulation and inhibition
Crystal structure of human carbonic
anhydrase II at 1.95 Å resolution in complex with 667-coumate, a novel
Adenophostin A and analogues modified at the adenine moiety:
synthesis, conformational analysis and biological activity.
First crystal structures of human carbonic
anhydrase II in complex with dual aromatase-steroid sulfatase inhibitors.
Novel and potent 17 -hydroxysteroid
dehydrogenase type 1 inhibitors.
Rapid synthetic route towards structurally
modified derivatives of cyclic adenosine 5'-diphosphate ribose.
Synthesis of stable and cell-type selective
analogues of cyclic ADP-ribose, a Ca2+-mobilizing second messenger.
Structure-activity relationship of the N1-ribose
Interaction of the catalytic domain of
Inositol 1,4,5-trisphosphate 3-kinase A with inositol phosphate analogues.
A-ring substituted estrogen-3-O-sulfamates:
Potent multi-targeted anti-cancer agents.
E-Ring modified steroids as novel potent
inhibitors of 17 -hydroxysteroid dehydrogenase type
Inhibition of the Phosphatidylinositol
3-kinase/Akt pathway by inositol pentakisphosphate results in antiangiogenic and antitumour effects.
Inhibition of in vitro angiogenesis by
2-methoxy- and 2-ethyl-estrogen sulfamates.
Carbonic anhydrase inhibitors: X-ray
crystallographic structure of the adduct of human isozyme II with EMATE, a
dual inhibitor or carbonic anhydrases and steroid sulfatase.
promotes apoptosis through the PI 3-K/Akt pathway.
Dimers of D-myo-inositol
1,4,5-trisphosphate: Design, synthesis and interaction with Ins(1,4,5)P3
1,4,5-trisphosphate as a novel ligand for conjugation: physicochemical
properties and synthesis of a new Ins(1,4,5)P3 affinity matrix.
derivatives: synthesis of a novel class of multi-targeted anti-tumour agents.
2-MeOE2bisMATE induces caspase-dependent
apoptosis in CAL51 breast cancer cells and overcomes resistance to TRAIL via
cooperative activation of caspases.
Amplification and propagation of pacemaker
Ca2+ signals by cyclic ADP-ribose and the type 3 ryanodine receptor in T
Inositol trisphosphate analogues selective
for types I and II inositol trisphosphate receptors exert differential
effects on vasopressin-stimulated Ca2+ inflow and Ca2+ release from
intracellular stores in rat hepatocytes.
Novel 18 -Glycyrrhetinic
acid analogues as potent and selective inhibitors of 11 -hydroxysteroid
Chemical synthesis of the second messenger
nicotinic acid adenine dinucleotide phosphate by total synthesis of
nicotinamide adenine dinucleotide phoshate.
Regulation of casein kinase-2 (CK2)
activity by inositol phosphates.
1,3,4,5-tetrakisphosphate, a mimic of D-myo-inositol
1,3,4,5-tetrakisphosphate: biological activity and pH-dependent
Aplysia californica mediated
cyclisation of novel 3'-modified NAD analogues: A role for hydrogen bonding
in the recognition of cyclic adenosine 5'-diphosphate ribose.
Synthesis and Ca2+ mobilising
activity of purine-modified mimics of adenophostin
A: A model for the adenophostin-Ins(1,4,5)P3
Identification of mammalian Vps24p as an
effector of phosphatidylinositol 3,5 bisphosphate-dependent endosome
Convergent synthesis and unexpected Ca2+-mobilizing
activity of the 8-substituted analogues of cyclic ADP-carbocyclic ribose, a
stable mimic of Ca2+-mobilizing second messenger cyclic
First enzymatic synthesis of an N1-cyclised
cADPR (cyclic-ADP ribose) analogue with an
hypoxanthine partial structure: discovery of a membrane permeant cADPR agonist.
First dual aromatase-steroid sulfatase
D-ring modified estrone
derivatives as novel potent inhibitors of steroid sulfatase.
Estrone 3-sulfate mimics, inhibitors of estrone
sulfatase activity: Homology model construction and docking studies
Interactions of inositol
1,4,5-trisphosphate receptors with synthetic poly(ethylene glycol)-linked
dimmers of IP3 suggest close spacing of the IP3-binding
Novel hydrolysis-resistant analogues of
cyclic ADP-ribose: Modification of the "northern" ribose and
calcium release activity.
Regulation of Ins(3,4,5,6)P4 signaling by a reversible kinase/phosphatase.
Total synthesis of nucleobase-modified adenophostin A mimics.
of D-myo-inositol 1,4,5-trisphosphate related to adenophostin A: Synthesis and biological activity.
Structural determinants of adenophostin A activity at inositol trisphosphate
Nicotinic acid adenine dinucleotide phosphate
(NAADP+) is an essential regulator of T-lymphocyte Ca2+-signaling.
Synthesis of potent agonists of the D-myo-inositol 1,4,5-trisphosphate receptor based on
clustered disaccharide polyphosphate analogues of adenophostin
InsP4 facilitates store-operated
calcium influx by inhibition of InsP3 5-phosphatase.
Structure of the PH domain from Bruton's tyrosine kinase in complex with inositol
Regulation of calcium signalling in T
lymphocytes by the second messenger cyclic ADP-ribose.
Evidence of a role for cyclic ADP-ribose in
long-term synaptic depression in hippocampus.
Steroidal and non-steroidal sulfamates as potent inhibitors of steroid sulfatase.
restricted cyclic phosphate analogue of inositol trisphosphate: synthesis and
Total synthesis from D-xylose of chiral,
ring-contracted 1D-myo-inositol 1,4,5-trisphosphate and
1,3,4,5-tetrakisphosphate analogues with C-2 excised.
Disaccharide polyphosphates based upon adenophostin A activate hepatic d-myo-inositol
Structural analogues of D-myo- inositol 1,4,5-trisphosphate and adenophostin
A: Recognition by cerebellar and platelet inositol 1,4,5-trisphosphate
Rapid synthesis of the enantiomers of myo-inositol 1,3,4,5-tetrakisphosphate by direct chiral desymmetrization of myo-inositol
Isotopic enrichment by asymmetric deuteriation. An investigation of the synthesis of deuteriated (S)-(-)-methylsuccinic
acids from itaconic acid.
Cyclic aristeromycin diphosphate ribose: A potent and poorly hydrolysable Ca2+-mobilising mimic of cyclic adenosine diphosphate ribose.
V C Bailey, S M Fortt, R J Summerhill, A Galione and B V L Potter, FEBS Lett (1996) 379, 227-230.
Active site-directed inhibition of estrone sulfatase by non-steroidal coumarin sulfamates.
L W L Woo, A Purohit, M J Reed and B V L Potter, J Med Chem (1996) 39, 1349-1351.
Synthesis of D-2-deoxy-myo-inositol 1,3,4,5-tetrakisphosphate from D-glucose.
D J Jenkins, D Dubreuil and B V L Potter, J Chem Soc Perkin Trans I (1996) 1365-1372.
A Tandem Horner-Emmons olefination-conjugate addition approach to the synthesis of 1,5-disubstituted-6-azabicyclo[3.2.1]octanes based on the AE ring structure of the norditerpenoid alkaloid methyllycaconitine.
D J Callis, N F Thomas, D P J Pearson and B V L Potter, J Org Chem (1996) 61, 4634-4640.
A specific cyclic ADP-ribose antagonist inhibits cardiac excitation-contraction coupling.
S Rakovic, A Galione, G A Ashamu, B V L Potter and D A Terrar, Curr Biol, (1996) 6, 989-996.
Chiral cyclopentane-based mimics of D-myo-inositol-1,4,5-trisphosphate from D-glucose.
D J Jenkins, A M Riley and B V L Potter, J Org Chem (1996) 61, 7719-7726.