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 475 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-), 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 and Associate Member, Department of Pharmacology, Oxford. He is named in the “H-index ranking of living chemists” listing (h-index 56).
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 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
Inositol phosphate-mediated cellular
Cyclic ADP-ribose - a new
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.
This project is supported by a Wellcome Trust Project Grant.
NAADP - a
new second messenger
Anticancer drug design, discovery & translational medicine
Steroid Sulfatase Inhibitors:
The STS inhibitor PGL2001, designed at
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 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.
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
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.
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 type 1 has 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. 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.
CD38 Structure-Based Inhibitor Design using the N1-Cyclic Inosine 5¢-Diphosphate Ribose Template
C Moreau, Q Liu, R Graeff, G K Wagner, J Swarbrick, M P Thomas, S Shuto, H-C. Lee, Q Hao, and B V L Potter PLOS ONE (2013) in press
NAADP mediated calcium signalling and arrhythmias in the heart evoked by β-adrenergic stimulation
M Nebel, A Schwörer, D Warszta, C C Siebrands, A-C Limbrock, J M Swarbrick, R Fliegert, M Hohenegger, A Geisler, L Herich, S Schlegel, L Carrier, T Eschenhagen, BVL Potter, H Ehmke, and A H Guse J Biol Chem (2013) in press [JBC Paper of the Week].
Design and synthesis of cyclic ADP-4-thioribose as a stable equivalent of cyclic ADP-ribose, a Ca2+-mobilizing second messenger
T Tsuzuki, N Sakaguchi, T Kudoh, S Takano, M Uehara, T Murayama, T Sakurai, M Hashii, H Higashida, K Weber, A H Guse, T Kameda, T Hirokawa, Y Kumaki, B V L Potter, H Fukuda, M Arisawa, and Shuto Angew Chem Int Edn (2013) in press.
The Structural Biology of Estrogen Metabolism
M P Thomas and B V L Potter J Steroid Biochem Mol Biol (2013) in press.
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 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 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
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 Metabolism.
Selective Determinants of IP3
and Adenophostin A Interactions with Type 1 IP3 Receptors.
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
mediated Ca2+ signaling in effector cells regulates autoimmunity
of the nervous system.
Discovery 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
Chimeric Microtubule Disruptors.
Synthesis, Antitubulin 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.
diphosphoribose: towards a selective cyclic ADP-ribose agonist.
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
Steroid sulphatase 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 5-phosphatase.
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 Aryl Sulfamates.
Base-Modified Analogs of Adenophostin A as High-Affinity Agonists of the
D-myo-Inositol Trisphosphate Receptor: In Vitro Evaluation and Molecular
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 Anti-cancer agents.
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 substrate analog.
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.
2-fluoroadenine 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
Rapid and efficient routes to
phosphatidylinositol 3,4,5-trisphosphates via myo-inositol orthobenzoate.
2-Substituted estradiol 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 and physicochemistry.
Cellular effects and metabolic stability of
N1-cyclic inosine diphosphoribose and its derivatives.
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 1.
Guanophostin A: Synthesis and evaluation of
a high affinity agonist of the D-myo-inositol 1,4,5 trisphosphate receptor.
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.
scyllo-Inositol pentakisphosphate 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.
Chiral desymmetrisation of myo-inositol
1,3,5-orthobenzoate gives rapid access to precursors for second messenger
Modification of estrone at the 6, 16, 17
positions: Novel potent inhibitors of 17 -hydroxysteroid dehydrogenase type
Unusual entry to the novel
8-halo-N1-ribosyl hypoxanthine system by degradation of a cyclic
adenosine-5'-diphosphate ribose analogue.
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
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 moiety.
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 1.
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.
Inositol pentakisphosphate 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.
2-Alkylsulfanyl estrogen 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 dehydrogenases.
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 receptor interaction.
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.
Bicyclic analogs of D-myo-inositol
1,4,5-trisphosphate related to adenophostin A: Synthesis and biological
Structural determinants of adenophostin A
activity at inositol trisphosphate receptors.
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 A.
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 1,3,4,5-tetrakisphosphate.
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.
A conformationally restricted cyclic
phosphate analogue of inositol trisphosphate: synthesis and physicochemical
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 1,4,5-trisphosphate receptors.
Structural analogues of D-myo- inositol
1,4,5-trisphosphate and adenophostin A: Recognition by cerebellar and
platelet inositol 1,4,5-trisphosphate receptors.
Rapid synthesis of the enantiomers of
myo-inositol 1,3,4,5-tetrakisphosphate by direct chiral desymmetrization of
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.