Review
Pharmacology & Pharmacy
Lavinia Casati, Samuele Ciceri, Roberto Maggi, Daniele Bottai
Summary: GnRH is a decapeptide responsible for the control of reproductive functions. It plays a role in infertility diagnosis and treatment, and also has effects on various organs and tissues in the body.
BIOCHEMICAL PHARMACOLOGY
(2023)
Review
Cell Biology
Carsten Gruendker, Guenter Emons
Summary: The HPG axis regulates the female menstrual cycle through GnRH, which can impact ovarian cancer either indirectly through the HPG axis or directly through receptors on the surface of tumor cells.
Review
Cell Biology
Gunter Emons, Carsten Gruendker
Summary: Endometrial cancer expresses GnRH and its receptor, which can regulate proliferation, the cell cycle, and apoptosis. GnRH agonists are used in fertility preserving therapy for early EC, but show limited activity in advanced or recurrent EC. Further clinical trials exploring the GnRH-system in EC may be beneficial.
Article
Biochemistry & Molecular Biology
Georgia Biniari, Christos Markatos, Agathi Nteli, Haralambos Tzoupis, Carmen Simal, Alexios Vlamis-Gardikas, Vlasios Karageorgos, Ioannis Pirmettis, Panagiota Petrou, Maria Venihaki, George Liapakis, Theodore Tselios
Summary: Gonadotropin-releasing hormone (GnRH) plays a key role in regulating human reproduction and fertility. GnRH receptor type I (GnRHR I), expressed on both healthy and cancer cells, is a potential target for anti-cancer drugs. This study synthesized a series of anthraquinone/mitoxantrone-GnRH conjugates and found promising results in terms of binding affinity and potential for further pharmacological evaluation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Neurosciences
Mattia Camera, Isabella Russo, Valentina Zamboni, Alessandra Ammoni, Simona Rando, Alessandro Morellato, Irene Cimino, Costanza Angelini, Paolo Giacobini, Roberto Oleari, Federica Amoruso, Anna Cariboni, Isabelle Franceschini, Emilia Turco, Paola Defilippi, Giorgio R. Merlo
Summary: The absence of the p140Cap gene in mice leads to abnormalities in fertility, puberty development, and hormone secretion. This may be due to its role in the development of the hypothalamic gonadotropic system and modulation of glutamatergic signaling.
FRONTIERS IN NEUROSCIENCE
(2022)
Article
Obstetrics & Gynecology
Tasuku Harada, Yutaka Osuga, Yusuke Suzuki, Masaki Fujisawa, Motoko Fukui, Jo Kitawaki
Summary: This study evaluated the efficacy and safety of 40-mg relugolix compared with leuprorelin in treating endometriosis-associated pain. The results demonstrated that relugolix was noninferior to leuprorelin in relieving pelvic pain, and both medications had comparable safety profiles.
FERTILITY AND STERILITY
(2022)
Article
Cell Biology
Mor Kishner, Libat Habaz, Lana Meshnik, Tomer Dvir Meidan, Alexandra Polonsky, Anat Ben-Zvi
Summary: This study found that GnRH receptors in Caenorhabditis elegans regulate protein homeostasis in different somatic tissues during the transition to adulthood. They modulate the activity of transcription factors and affect reproductive capacity. This suggests that GnRH-like signaling plays a crucial regulatory role in controlling reproduction and quality control.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
David Ben-Menahem
Summary: Genomic and phylogenetic analyses of various invertebrate phyla have revealed the existence of genes related to vertebrate's decapeptide gonadotropin-releasing hormone (GnRH) and its receptor genes. Research has identified AKH and CRZ in insects, which have similar sizes to GnRH and serve as neurohormones, with pleiotropic activities in metabolism and stress responses.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Obstetrics & Gynecology
Yutaka Osuga, Yoshifumi Seki, Masataka Tanimoto, Takeru Kusumoto, Kentarou Kudou, Naoki Terakawa
Summary: This study evaluated the efficacy and safety of relugolix in treating endometriosis-associated pain, showing that oral administration of relugolix alleviated pain in a dose-response manner and was generally well tolerated. Relugolix demonstrated efficacy and safety comparable to leuprorelin, another treatment option.
FERTILITY AND STERILITY
(2021)
Review
Obstetrics & Gynecology
Hailan Yan, Jinghua Shi, Xiaoyan Li, Yi Dai, Yushi Wu, Jing Zhang, Zhiyue Gu, Chenyu Zhang, Jinhua Leng
Summary: Oral GnRH antagonists are effective in treating pain and dysmenorrhea associated with endometriosis, but higher doses may be associated with more adverse effects.
FERTILITY AND STERILITY
(2022)
Article
Geriatrics & Gerontology
Dorota Walkiewicz, Zofia Wicik, Monika Puzianowska-Kuznicka
Summary: The study identified pathways associated with age-related changes in human B lymphocytes, including the gonadotropin-releasing hormone receptor (GnRHR) pathway, which is involved in both aging and lymphocyte activation. Inhibition of the GnRHR pathway reduced cell proliferation, increased apoptosis, and led to decreased immunoglobulin G synthesis in B lymphocytes, with a more pronounced effect in centenarian cells compared to young cells.
EXPERIMENTAL GERONTOLOGY
(2021)
Article
Agriculture, Dairy & Animal Science
Julia Schutz, Jurn Rudolph, Adrian Steiner, Esther Rothenanger, Jurg Husler, Gaby Hirsbrunner
Summary: The study successfully postponed puberty in beef heifers using the Improvac(R) vaccine, preventing unwanted pregnancies and inbreeding. None of the vaccinated calves exceeded a progesterone value >1 ng/mL until the scheduled age of slaughter, compared to 56.5% in the control group.
Article
Medicine, Research & Experimental
Ana Salas, Patricia Garcia-Garcia, Patricia Diaz-Rodriguez, Carmen Evora, Teresa A. Almeida, Araceli Delgado
Summary: Currently, surgical removal is the most common treatment for symptomatic leiomyomas due to the limited treatment options available. Previous studies have shown that GnRH agonists and antagonists can induce cell death and decrease extracellular synthesis in leiomyoma cells. In this study, the GnRH antagonist ganirelix was encapsulated in PLGA microspheres and contained in an alginate scaffold, resulting in significant cell death in 50-55% of tumor cells. Although there were no changes in the expression of extracellular matrix genes, a transcription factor involved in osmotic stress and tumor size showed decreased expression. Interestingly, all tumors analyzed experienced apoptosis regardless of the original driver mutation. These findings suggest that local therapy with ganirelix could effectively reduce the size of uterine leiomyomas.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Review
Endocrinology & Metabolism
Hsien-Ming Wu, Hsun-Ming Chang, Peter C. K. Leung
Summary: Extra-hypothalamic GnRH and extra-pituitary GnRH receptors exist in multiple human reproductive tissues, facilitating the development of new analogs and regulators for clinical application in assisted reproductive technology. GnRH signaling primarily controls female reproduction, with potential for the treatment of reproductive disorders and continuous development of new GnRH analogs. Upstream regulators of GnRH, such as kisspeptin and neurokinin B, offer promising potential for controlling the hypothalamus-pituitary-ovarian axis.
FRONTIERS IN NEUROENDOCRINOLOGY
(2021)
Article
Medicine, General & Internal
Xin Li, Feifei Sun, Xiaolei Zhang, Pingping Lin, Kai Shen, Yu Shen, Lingyu Ma, Yu Cao, Chenjing Wang
Summary: This study evaluated the safety, pharmacokinetics, and pharmacodynamics of an oral small molecule GnRH antagonist, SHR7280, in healthy men. The results demonstrated that SHR7280 had an acceptable safety profile and favorable pharmacokinetic and pharmacodynamic characteristics within a dose range of 100 to 1000 mg BID. This study proposes a rationale for further investigation of SHR7280 as a potential androgen deprivation therapy.
Article
Chemistry, Medicinal
Saleh Ahmed, Andrew Ayscough, Greg R. Barker, Hannah E. Canning, Richard Davenport, Robert Downham, David Harrison, Kerry Jenkins, Natasha Kinsella, David G. Livermore, Susanne Wright, Anthony D. Ivetac, Robert Skene, Steven J. Wilkens, Natalie A. Webster, Alan G. Hendrick
JOURNAL OF MEDICINAL CHEMISTRY
(2017)
Article
Multidisciplinary Sciences
Isaia Barbieri, Konstantinos Tzelepis, Luca Pandolfini, Junwei Shi, Gonzalo Millan-Zambrano, Samuel C. Robson, Demetrios Aspris, Valentina Migliori, Andrew J. Bannister, Namshik Han, Etienne De Braekeleer, Hannes Ponstingl, Alan Hendrick, Christopher R. Vakoc, George S. Vassiliou, Tony Kouzarides
Article
Biochemistry & Molecular Biology
Eimear Howley, Michael Bestwick, Rosa Fradley, Helen Harrison, Mathew Leveridge, Kengo Okada, Charlotte Fieldhouse, Will Farnaby, Hannah Canning, Andy P. Sykes, Kevin Merchant, Katherine Hazel, Catrina Kerr, Natasha Kinsella, Louise Walsh, David G. Livermore, Isaac Hoffman, Jonathan Ellery, Phillip Mitchell, Toshal Patel, Mark Carlton, Matt Barnes, David J. Miller
NEUROCHEMICAL RESEARCH
(2017)
Article
Chemistry, Medicinal
Daniel P. Teufel, Gavin Bennett, Helen Harrison, Katerine Van Rietschoten, Silvia Pavan, Catherine Stace, Francois Le Floch, Tine Van Bergen, Elke Vermassen, Philippe Barbeaux, Tjing-Tjing Hu, Jean H. M. Feyen, Marc Vanhove
JOURNAL OF MEDICINAL CHEMISTRY
(2018)
Article
Oncology
Matthias Eder, Silvia Pavan, Ulrike Bauder-Wuest, Katerine van Rietschoten, Ann-Christin Baranski, Helen Harrison, Spencer Campbell, Catherine L. Stace, Edward H. Walker, Liuhong Chen, Gavin Bennett, Gemma Mudd, Ursula Schierbaum, Karin Leotta, Uwe Haberkorn, Klaus Kopka, Daniel P. Teufel
Article
Multidisciplinary Sciences
Aditi Singh, Adrienne Vancura, Rafal K. Woycicki, Daniel J. Hogan, Alan G. Hendrick, Mariusz Nowacki
Article
Biochemistry & Molecular Biology
Luca Pandolfini, Isaia Barbieri, Andrew J. Bannister, Alan Hendrick, Byron Andrews, Natalie Webster, Pierre Murat, Pia Mach, Rossella Brandi, Samuel C. Robson, Valentina Migliori, Andrej Alendar, Mara d'Onofrio, Shankar Balasubramanian, Tony Kouzarides
Article
Biochemistry & Molecular Biology
Lindsey Van Haute, Alan G. Hendrick, Aaron R. D'Souza, Christopher A. Powell, Pedro Rebelo-Guiomar, Michael E. Harbour, Shujing Ding, Ian M. Fearnley, Byron Andrews, Michal Minczuk
NUCLEIC ACIDS RESEARCH
(2019)
Article
Biochemistry & Molecular Biology
Felix Hagelskamp, Kayla Borland, Jillian Ramos, Alan G. Hendrick, Dragony Fu, Stefanie Kellner
NUCLEIC ACIDS RESEARCH
(2020)
Article
Chemistry, Medicinal
James M. Wagstaff, Matthew Balmforth, Nick Lewis, Rachel Dods, Catherine Rowland, Katerine van Rietschoten, Liuhong Chen, Helen Harrison, Michael J. Skynner, Michael Dawson, Gabriela Ivanova-Berndt, Paul Beswick
ACS INFECTIOUS DISEASES
(2020)
Article
Oncology
Punit Upadhyaya, Johanna Lahdenranta, Kristen Hurov, Sailaja Battula, Rachel Dods, Eric Haines, Marianna Kleyman, Julia Kristensson, Jessica Kublin, Rachid Lani, Jun Ma, Gemma Mudd, Elizabeth Repash, Katerine Van Rietschoten, Tom Stephen, Fanglei You, Helen Harrison, Liuhong Chen, Kevin McDonnell, Philip Brandish, Nicholas Keen
Summary: Linking Bicycles against costimulatory receptors (e.g., CD137) to Bicycles against tumor antigens (e.g., EphA2) created potent agonists that selectively activated the receptors in the presence of tumor cells expressing these antigens.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Multidisciplinary Sciences
Eliza Yankova, Wesley Blackaby, Mark Albertella, Justyna Rak, Etienne De Braekeleer, Georgia Tsagkogeorga, Ewa S. Pilka, Demetrios Aspris, Dan Leggate, Alan G. Hendrick, Natalie A. Webster, Byron Andrews, Richard Fosbeary, Patrick Guest, Nerea Irigoyen, Maria Eleftheriou, Malgorzata Gozdecka, Joao M. L. Dias, Andrew J. Bannister, Binje Vick, Irmela Jeremias, George S. Vassiliou, Oliver Rausch, Konstantinos Tzelepis, Tony Kouzarides
Summary: The study identified a highly potent and selective catalytic inhibitor of METTL3, STM2457, which shows potential therapeutic value in treating AML. Treatment with this inhibitor leads to reduced AML growth, increased differentiation and apoptosis, and decreased m(6)A levels on leukemogenic mRNAs. In vivo pharmacological inhibition of METTL3 results in impaired engraftment and prolonged survival in mouse models of AML.
Article
Cell Biology
Hannah M. Burgess, Daniel P. Depledge, Letitia Thompson, Kalanghad Puthankalam Srinivas, Rebecca C. Grande, Elizabeth I. Vink, Jonathan S. Abebe, Wesley P. Blackaby, Alan Hendrick, Mark R. Albertella, Tony Kouzarides, Kenneth A. Stapleford, Angus C. Wilson, Ian Mohr
Summary: The cellular m(6)A modification machinery impacts coronavirus replication, and targeting the m(6)A pathway could potentially restrict coronavirus reproduction. This study showed that SARS-CoV-2 and HCoV-OC43 replication can be suppressed by depleting METTL3 or cytoplasmic m(6)A reader proteins. Additionally, mapping m(6)A modification sites on viral RNAs revealed the influence of host m(6)A pathway components on beta-coronavirus replication.
GENES & DEVELOPMENT
(2021)
Article
Oncology
Michael Rigby, Gavin Bennett, Liuhong Chen, Gemma E. Mudd, Helen Harrison, Paul J. Beswick, Katerine Van Rietschoten, Sophie M. Watcham, Heather S. Scott, Amy N. Brown, Peter U. Park, Carly Campbell, Eric Haines, Johanna Lahdenranta, Michael J. Skynner, Phil Jeffrey, Nicholas Keen, Kevin Lee
Summary: Nectin-4 is overexpressed in multiple tumor types, and BT8009, a new drug targeting Nectin-4, exhibits significant antitumor activity and good tolerability in solid tumors expressing Nectin-4.
MOLECULAR CANCER THERAPEUTICS
(2022)