Professor Matthew J. Fuchter

Meyners C, Baud MGJ, Fuchter MJ, Meyer Almes F-Jet al., 2014, Thermodynamics of ligand binding to histone deacetylase like amidohydrolase from Bordetella/Alcaligenes, Journal of Molecular Recognition, Vol: 27, Pages: 160-172

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Srimongkolpithak N, Sundriyal S, Li F, Vedadi M, Fuchter MJet al., 2014, Identification of 2,4-diamino-6,7-dimethoxyquinoline derivatives as G9a inhibitors, MEDCHEMCOMM, Vol: 5, Pages: 1821-1828, ISSN: 2040-2503

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• Citations: 31

Berger RJF, Fuchter MJ, Krossing I, Rzepa HS, Schaefer J, Scherer Het al., 2014, Gold(I) mediated rearrangement of [7]-helicene to give a benzo[<i>cd</i>]pyrenium cation embedded in a chiral framework, CHEMICAL COMMUNICATIONS, Vol: 50, Pages: 5251-5253, ISSN: 1359-7345

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• Citations: 7

Cherblanc FL, Lo Y-P, Herrebout WA, Bultinck P, Rzepa HS, Fuchter MJet al., 2013, Mechanistic and Chiroptical Studies on the Desulfurization of Epidithiodioxopiperazines Reveal Universal Retention of Configuration at the Bridgehead Carbon Atoms, JOURNAL OF ORGANIC CHEMISTRY, Vol: 78, Pages: 11646-11655, ISSN: 0022-3263

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• Citations: 14

Cherblanc FL, Chapman KL, Reid J, Borg AJ, Sundriyal S, Alcazar-Fuoli L, Bignell E, Demetriades M, Schofield CJ, DiMaggio PA, Brown R, Fuchter MJet al., 2013, On the Histone Lysine Methyltransferase Activity of Fungal Metabolite Chaetocin, JOURNAL OF MEDICINAL CHEMISTRY, Vol: 56, Pages: 8616-8625, ISSN: 0022-2623

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• Citations: 48

Judge DK, Haycock P, Richardson RD, Fuchter MJet al., 2013, <i>ortho</i>-Substituted 1,8-Diarylnaphthalenes: Conformational Thermodynamics and Kinetics, SYNLETT, Vol: 24, Pages: 2365-2369, ISSN: 0936-5214

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• Citations: 9

Kaliszczak M, Patel H, Kroll SHB, Carroll L, Smith G, Delaney S, Heathcote DA, Bondke A, Fuchter MJ, Coombes RC, Barrett AGM, Ali S, Aboagye EOet al., 2013, Development of a cyclin-dependent kinase inhibitor devoid of ABC transporter-dependent drug resistance, British Journal of Cancer, Vol: 109, Pages: 2356-2367, ISSN: 1532-1827

background: Cyclin-dependent kinases (CDKs) control cell cycle progression, RNA transcription and apoptosis, making them attractive targets for anticancer drug development. Unfortunately, CDK inhibitors developed to date have demonstrated variable efficacy.methods: We generated drug-resistant cells by continuous low-dose exposure to a model pyrazolo[1,5-a]pyrimidine CDK inhibitor and investigated potential structural alterations for optimal efficacy.results: We identified induction of the ATP-binding cassette (ABC) transporters, ABCB1 and ABCG2, in resistant cells. Assessment of features involved in the ABC transporter substrate specificity from a compound library revealed high polar surface area (>100 Å2) as a key determinant of transporter interaction. We developed ICEC-0782 that preferentially inhibited CDK2, CDK7 and CDK9 in the nanomolar range. The compound inhibited phosphorylation of CDK substrates and downregulated the short-lived proteins, Mcl-1 and cyclin D1. ICEC-0782 induced G2/M arrest and apoptosis. The permeability and cytotoxicity of ICEC-0782 were unaffected by ABC transporter expression. Following daily oral dosing, the compound inhibited growth of human colon HCT-116 and human breast MCF7 tumour xenografts in vivo by 84% and 94%, respectively.conclusion: We identified a promising pyrazolo[1,5-a]pyrimidine compound devoid of ABC transporter interaction, highly suitable for further preclinical and clinical evaluation for the treatment of cancer.

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Yang Y, Correa da Costa R, Fuchter MJ, Campbell AJet al., 2013, Circularly polarized light detection by a chiralorganic semiconductor transistor, Nature Photonics, Vol: 7, Pages: 634-638

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Yang Y, da Costa RC, Smilgies D-M, Campbell AJ, Fuchter MJet al., 2013, Induction of Circularly Polarized Electroluminescence from an Achiral Light-Emitting Polymer via a Chiral Small-Molecule Dopant, ADVANCED MATERIALS, Vol: 25, Pages: 2624-2628, ISSN: 0935-9648

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• Citations: 298

Weimar M, Correa da Costa R, Lee F-H, Fuchter MJet al., 2013, A Scalable and Expedient Route to 1‐Aza[6]helicene Derivatives and Its Subsequent Application to a Chiral-Relay Asymmetric Strategy, Organic Letters, Vol: 15, Pages: 1706-1709

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Cherblanc F, Chapman KL, Brown R, Fuchter MJet al., 2013, Chaetocin is a nonspecific inhibitor of histone lysine methyltransferases, Nature Chemical Biology, Vol: 9, Pages: 136-137

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Baud MGJ, Leiser T, Petrucci V, Gunaratnam M, Neidle S, Meyer-Amles FJ, Fuchter MJet al., 2013, Thioester derivatives of the natural product psammaplin A as potent histone deacetylase inhibitors, Beilstein Journal of Organic Chemistry, Vol: 9, Pages: 81-88

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Baud MGJ, Haus P, Leiser T, Meyer-Almes F-J, Fuchter MJet al., 2013, Highly Ligand Efficient and Selective <i>N</i>-2(Thioethyl)picolinamide Histone Deacetylase Inhibitors Inspired by the Natural Product Psammaplin A, CHEMMEDCHEM, Vol: 8, Pages: 149-156, ISSN: 1860-7179

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• Citations: 17

Cherblanc FL, Davidson RWM, Di Fruscia P, Srimongkolpithak N, Fuchter MJet al., 2013, Perspectives on natural product epigenetic modulators in chemical biology and medicine, NATURAL PRODUCT REPORTS, Vol: 30, Pages: 605-624, ISSN: 0265-0568

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• Citations: 46

Weimar M, Fuchter MJ, 2013, Synthesis of sterically encumbered C10-arylated benzo[<i>h</i>]quinolines using <i>ortho</i>-substituted aryl boronic acids, ORGANIC & BIOMOLECULAR CHEMISTRY, Vol: 11, Pages: 31-34, ISSN: 1477-0520

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• Citations: 3

Fuchter MJ, Judge DK, Weimar M, White AJPet al., 2013, Stoichiometric C-H arylation of tricarbonyl(arene)-chromium complexes bearing pyridine directing groups, DALTON TRANSACTIONS, Vol: 42, Pages: 5615-5618, ISSN: 1477-9226

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• Citations: 4

Malmquist NA, Moss TA, Mecheri S, Scherf A, Fuchter MJet al., 2012, Small-molecule histone methyltransferase inhibitors display rapid antimalarial activity against all blood stage forms in <i>Plasmodium falciparum</i>, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 109, Pages: 16708-16713, ISSN: 0027-8424

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• Citations: 101

Forkel NV, Henderson DA, Fuchter MJ, 2012, Lanthanide Replacement in Organic Synthesis: Luche-Type Reduction of a,ß-Unsaturated Ketones in the Presence of Calcium triflate, Green Chemistry, Vol: 14, Pages: 2129-2132

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Cherblanc F, Chapman-Rothe N, Brown R, Fuchter MJet al., 2012, Current limitations and future opportunities for epigenetic therapies, Future Medicinal Chemistry, Vol: 4, Pages: 425-446

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Fuchter MJ, Weimar M, Yang X, Judge DK, White AJPet al., 2012, An Unusual Oxidative Rearrangement of [7]-Helicene, Tetrahedron Letters, Vol: 53, Pages: 1108-1111

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Baud MGJ, Leiser T, Haus P, Samlal S, Wong AC, Wood RJ, Petrucci V, Gunaratnam M, Hughes SM, Buluwela L, Turlais F, Neidle S, Meyer-Almes F-J, White AJP, Fuchter MJet al., 2012, Defining the Mechanism of Action and Enzymatic Selectivity of Psammaplin A against Its Epigenetic Targets, JOURNAL OF MEDICINAL CHEMISTRY, Vol: 55, Pages: 1731-1750, ISSN: 0022-2623

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• Citations: 81

Di Fruscia P, Ho K-K, Laohasinnarong S, Khonghow M, Kroll SHB, Islam SA, Sternberg MJE, Schmidtkunz K, Jung M, Lam EW-F, Fuchter MJet al., 2012, The discovery of novel 10,11-dihydro-5H-dibenz[b,f]azepine SIRT2 inhibitors, MedChemComm

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Fuchter MJ, Schaefer J, Judge DK, Wardzinski B, Weimar M, Krossing Iet al., 2012, [7]-Helicene: a chiral molecular tweezer for silver(I) salts, DALTON TRANSACTIONS, Vol: 41, Pages: 8238-8241, ISSN: 1477-9226

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• Citations: 47

Levy J-N, Latham CM, Roisin L, Kandziora N, Di Fruscia P, White AJP, Woodward S, Fuchter MJet al., 2012, The design and synthesis of novel IBiox N-heterocyclic carbene ligands derived from substituted amino-indanols, ORGANIC & BIOMOLECULAR CHEMISTRY, Vol: 10, Pages: 512-515, ISSN: 1477-0520

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• Citations: 21

Cherblanc F, Lo Y-P, De Gussem E, Alcazar-Fuoli L, Bignell E, He Y, Chapman-Rothe N, Bultinck P, Herrebout WA, Brown R, Rzepa HS, Fuchter MJet al., 2011, On the Determination of the Stereochemistry of Semisynthetic Natural Product Analogues using Chiroptical Spectroscopy: Desulfurization of Epidithiodioxopiperazine Fungal Metabolites, CHEMISTRY-A EUROPEAN JOURNAL, Vol: 17, Pages: 11868-11875, ISSN: 0947-6539

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• Citations: 27

Scherf A, Malmquist NA, Moss TA, Fuchter MJet al., 2011, The study of antigenic variation in <i>Plasmodium falciparum</i>: mind games or a novel therapeutic approach, 36th FEBS Congress of the Biochemistry for Tomorrows Medicine, Publisher: WILEY-BLACKWELL, Pages: 62-63, ISSN: 1742-464X

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Haider S, Joseph CG, Neidle S, Fierke CA, Fuchter MJet al., 2011, On the function of the internal cavity of histone deacetylase protein 8: R37 is a crucial residue for catalysis, BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, Vol: 21, Pages: 2129-2132, ISSN: 0960-894X

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• Citations: 36

Baud MGJ, Leiser T, Meyer-Almes F-J, Fuchter MJet al., 2011, New synthetic strategies towards psammaplin A, access to natural product analogues for biological evaluation, ORGANIC & BIOMOLECULAR CHEMISTRY, Vol: 9, Pages: 659-662, ISSN: 1477-0520

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• Citations: 24

Heathcote DA, Patel H, Kroll SH, Hazel P, Periyasamy M, Alikian M, Kannegnti SK, Jogalekar AS, Scheiper B, Barbazanges M, Blum A, Brackow J, Siwicka A, Pace RD, Fuchter MJ, Snyder JP, Liotta DC, Freemont PS, Aboagye EO, Coombes RC, Barrett AG, Ali Set al., 2010, A novel pyrazolo[1,5-a]pyrimidine is a potent inhibitor of cyclin-dependent protein kinases 1, 2, and 9, which demonstrates antitumor effects in human tumor xenografts following oral administration, J Med Chem, Vol: 53, Pages: 8508-8522

Cyclin-dependent protein kinases (CDKs) are central to the appropriate regulation of cell proliferation, apoptosis, and gene expression. Abnormalities in CDK activity and regulation are common features of cancer, making CDK family members attractive targets for the development of anticancer drugs. Here, we report the identification of a pyrazolo[1,5-a]pyrimidine derived compound, 4k (BS-194), as a selective and potent CDK inhibitor, which inhibits CDK2, CDK1, CDK5, CDK7, and CDK9 (IC= 3, 30, 30, 250, and 90 nmol/L, respectively). Cell-based studies showed inhibition of the phosphorylation of CDK substrates, Rb and the RNA polymerase II C-terminal domain, down-regulation of cyclins A, E, and D1, and cell cycle block in the S and G/M phases. Consistent with these findings, 4k demonstrated potent antiproliferative activity in 60 cancer cell lines tested (mean GI= 280 nmol/L). Pharmacokinetic studies showed that 4k is orally bioavailable, with an elimination half-life of 178 min following oral dosing in mice. When administered at a concentration of 25 mg/kg orally, 4k inhibited human tumor xenografts and suppressed CDK substrate phosphorylation. These findings identify 4k as a novel, potent CDK selective inhibitor with potential for oral delivery in cancer patients.

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Fuchter MJ, 2010, Nazarov Cyclization, Name Reactions for Carbocyclic Ring Formations, Editors: Corey, Li, New York, Publisher: Wiley, Pages: 122-146, ISBN: 978-0-470-08506-6

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