Development and evaluation of 4-(pyrrolidin-3-yl)benzonitrile derivatives as inhibitors of lysine specific demethylase 1

Autor: Ulf Bremberg, Donald J. Ogilvie, Matthis Geitmann, Gary J. Spencer, Allan M. Jordan, Alison E. McGonagle, Daniel P. Mould, Tim C. P. Somervaille

Publikováno v: Mould, D, Bremberg, U, Jordan, A, Geitmann, M, Mcgonagle, A, Somervaille, T, Spencer, G & Ogilvie, D 2017, ' Development and evaluation of 4-(pyrrolidin-3-yl)benzonitrile derivatives as inhibitors of lysine specific demethylase 1 ', Bioorganic and Medicinal Chemistry Letters, vol. 27, no. 20, pp. 4755-4759 . https://doi.org/10.1016/j.bmcl.2017.08.052

As part of our ongoing efforts to develop reversible inhibitors of LSD1, we identified a series of 4-(pyrrolidin-3-yl)benzonitrile derivatives that act as successful scaffold-hops of the literature inhibitor GSK-690. The most active compound, 21g, de

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9637baa02993aca2f4c31426b4e8d485
https://doi.org/10.1016/j.bmcl.2017.08.052

Cell-active Small Molecule Inhibitors of the DNA-damage Repair Enzyme Poly(ADP-ribose) Glycohydrolase (PARG): Discovery and Optimization of Orally Bioavailable Quinazolinedione Sulfonamides

Autor: Julie A. Tucker, Ben Acton, Ian D. Waddell, Alexandra Stowell, Nicola Hamilton, Niall M. Hamilton, Kate M. Smith, Stuart Donald Jones, James R. Hitchin, Bohdan Waszkowycz, Alison E. McGonagle, Dominic I. James, Allan M. Jordan, Daniel P. Mould, Clifford David Jones, Colin Hutton, Helen F. Small, Emma E. Fairweather, Donald J. Ogilvie, Louise A. Griffiths

Publikováno v: Waszkowycz, B, Smith, K, Mcgonagle, A, Jordan, A, Acton, B, Fairweather, E, Griffiths, L, Hamilton, N M, Hamilton, N, Hitchin, J R, Hutton, C, James, D I, Jones, C D, Jones, S, Mould, D, Small, H F, Stowell, A, Tucker, J, Waddell, I & Ogilvie, D J 2018, ' Cell-active Small Molecule Inhibitors of the DNA-damage Repair Enzyme Poly(ADP-ribose) Glycohydrolase (PARG): Discovery and Optimization of Orally Bioavailable Quinazolinedione Sulfonamides ', Journal of Medicinal Chemistry, vol. 61, no. 23, pp. 10767–10792 . https://doi.org/10.1021/acs.jmedchem.8b01407

DNA damage repair enzymes are promising targets in the development of new therapeutic agents for a wide range of cancers and potentially other diseases. The enzyme poly(ADP-ribose) glycohydrolase (PARG) plays a pivotal role in the regulation of DNA r

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1e713bd6a754c7026f2f63ab3b3df4e2
https://doi.org/10.1021/acs.jmedchem.8b01407

Reversible Inhibitors of LSD1 as Therapeutic Agents in Acute Myeloid Leukemia: Clinical Significance and Progress to Date

Autor: Daniel P. Mould, Daniel H. Wiseman, Allan M. Jordan, Emma Williams, Alison E. McGonagle

Publikováno v: Medicinal Research Reviews. 35:586-618

In the 10 years since the discovery of lysine-specific demethylase 1 (LSD1), this epigenetic eraser has emerged as an important target of interest in oncology. More specifically, research has demonstrated that it plays an essential role in the self-r

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_________::828fbddecb775a493e0d2e60dc01c556
https://doi.org/10.1002/med.21334

Abstract 3714: Optimisation of quinazolinedione sulphonamides as novel inhibitors of poly(ADP Ribose) glycohydrolase (PARG)

Autor: Nicola Hamilton, Stuart Donald Jones, Ben Acton, Bohdan Waszkowycz, Helen F. Small, Katherine Clegg Smith, Allan M. Jordan, Daniel P. Mould, Julie A. Tucker, Donald J. Ogilvie, Ian D. Waddell, Dominic I. James, Alex Stowell, Alison E. McGonagle, Cliff Jones

Publikováno v: Cancer Research. 76:3714-3714

The macrodomain protein poly(ADP ribose) glycohydrolase (PARG) has been shown to be a critical component in the repair of single stand DNA breaks and counteracts the function of the ARTD family of poly(ADP ribose) polymerases, commonly known as the P

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_________::189433740f0d1df0d075fea4683860ac
https://doi.org/10.1158/1538-7445.am2016-3714

Abstract 778: The identification and structure-guided optimisation of potent and selective inhibitors of oncogenes in medullary thyroid carcinoma and lung adenocarcinoma

Autor: Samantha J R Fritzl, Kristin M. Goldberg, Stuart Donald Jones, Kate Bowler, Rebecca Newton, Helen F. Small, Ben Acton, Niall M. Hamilton, Gemma Hopkins, Nikki March, Ian D. Waddell, Alexandra Stowell, Roger J. Butlin, Bohdan Waszkowycz, Daniel P. Mould, Sarah Holt, Allan M. Jordan, Donald J. Ogilvie, Mandy Watson

Publikováno v: Cancer Research. 75:778-778

RET (REarranged during Transfection) is a receptor tyrosine kinase (TK), which plays pivotal roles in regulating cell survival, differentiation, proliferation, migration and chemotaxis. Activating mutations in RET (C634W and M918T) have been identifi

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_________::bab693c868b606cda874c3b98165e04e
https://doi.org/10.1158/1538-7445.am2015-778