Article
Chemistry, Medicinal
Nayara Braga Emidio, Hue N. T. Tran, Asa Andersson, Philip E. Dawson, Fernando Albericio, Irina Vetter, Markus Muttenthaler
Summary: The high susceptibility to proteolytic degradation in the gastrointestinal tract limits the therapeutic application of peptide drugs, such as linaclotide, for gastrointestinal disorders. Improvements in gastrointestinal stability through strategic modifications of linaclotide analogues can significantly enhance their therapeutic efficacy and create potential for the development of the next generation of orally administered peptide drugs for gastrointestinal disorders.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Maria Duszyn, Brygida Swiezawska-Boniecka, Aloysius Wong, Krzysztof Jaworski, Adriana Szmidt-Jaworska
Summary: Recent studies identified a novel receptor BdPepR2 in Brachypodium distachyon, showing both catalytic and kinase activity, with important implications for plant processes. Through bioinformatic analysis, a conserved core catalytic motif was designed, leading to the discovery of potential GCs in monocots.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biology
Maryam Alfalasi, Sarah Alzaabi, Linda Ostlundh, Rami H. Al-Rifai, Suhail Al-Salam, Paul Michel Mertes, Seth L. Alper, Elhadi H. Aburawi, Abdelouahab Bellou
Summary: This systematic review assessed the effect of inhibiting nitric oxide pathways on blood pressure and survival in animal models of anaphylactic shock (AS). The results showed that inhibition of nitric oxide pathways improved survival and/or blood pressure in some experimental conditions. However, there is insufficient evidence to support the use of this approach as a definitive treatment for AS in humans.
Review
Cardiac & Cardiovascular Systems
Alberto Aimo, Vincenzo Castiglione, Giuseppe Vergaro, Giorgia Panichella, Michele Senni, Carlo Mario Lombardi, Michele Emdin
Summary: Heart failure with reduced or preserved ejection fraction is associated with significant morbidity and mortality, warranting the search for novel therapeutic agents. The nitric oxide-soluble guanylate cyclase-cyclic guanosine monophosphate pathway is disrupted in heart failure, and sGC activators or stimulators may be effective in treating this condition. Vericiguat has shown safety and efficacy in patients with HFrEF, but caution is needed in its use.
HEART FAILURE REVIEWS
(2022)
Review
Oncology
Moein Piroozkhah, Ali Aghajani, Pooya Jalali, Arvin Shahmoradi, Mobin Piroozkhah, Younes Tadlili, Zahra Salehi
Summary: This systematic review focuses on the latest research on the guanylate cyclase-C (GC-C) signaling axis in colorectal cancer (CRC). The findings reveal that alterations in GC-C signaling compartments in CRC tissue have potential as diagnostic, prognostic, and therapeutic markers. Moreover, the GC-C signaling axis may be a promising target for treating CRC.
FRONTIERS IN ONCOLOGY
(2023)
Review
Cardiac & Cardiovascular Systems
Carlo Mario Lombardi, Giuliana Cimino, Matteo Pagnesi, Andrea Dell'Aquila, Daniela Tomasoni, Alice Ravera, Riccardo Inciardi, Valentina Carubelli, Enrico Vizzardi, Savina Nodari, Michele Emdin, Alberto Aimo
Summary: The NO-sGC-cGMP pathway plays a crucial role in cardiovascular function and is disrupted in heart failure. Both sGC activators and stimulators can modulate cGMP levels through different mechanisms, offering potential benefits for patients with heart failure.
CURRENT CARDIOLOGY REPORTS
(2021)
Article
Endocrinology & Metabolism
Aaron Otero, Sara Becerril, Marina Martin, Javier A. Cienfuegos, Victor Valenti, Rafael Moncada, Victoria Catalan, Javier Gomez-Ambrosi, Maria A. Burrell, Amaia Rodriguez, Gema Fruhbeck
Summary: Obesity leads to fat deposition in non-adipose organs, including the pancreas, which is associated with inflammation and beta-cell dysfunction. This study aimed to investigate the mechanisms behind the improvement of pancreas fat accumulation after bariatric surgery. It was found that sleeve gastrectomy reduced pancreas steatosis and inflammation, and upregulated GUCA2A and GUCY2C in the pancreas, which might contribute to the beneficial effects of bariatric surgery. Additionally, guanylin and uroguanylin were found to alleviate lipotoxicity in beta-cells and modulate insulin synthesis and release.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Gastroenterology & Hepatology
Lin Chang, Brian E. Lacy, Baha Moshiree, Amy Kassebaum, Jessica L. Abel, Jennifer Hanlon, Wilmin Bartolini, Ramesh Boinpally, Wieslaw Bochenek, Susan M. Fox, Madhuja Mallick, Ken Tripp, Nicholas Omniewski, Elizabeth Shea, Niels Borgstein
Summary: Linaclotide significantly improved abdominal symptoms related to constipation-predominant irritable bowel syndrome (IBS-C) compared to placebo, including bloating, discomfort, and pain. The study found that linaclotide had a higher overall change from baseline in abdominal score (AS) and a higher responder rate for abdominal symptoms improvement, with diarrhea being the most common side effect. The use of a novel multi-item AS derived from the Diary for IBS Symptoms-Constipation may be valuable in future clinical studies for IBS-C to measure meaningful improvements beyond traditional endpoints.
AMERICAN JOURNAL OF GASTROENTEROLOGY
(2021)
Article
Gastroenterology & Hepatology
William D. Chey, Gregory S. Sayuk, Wilmin Bartolini, David S. Reasner, Susan M. Fox, Wieslaw Bochenek, Ramesh Boinpally, Elizabeth Shea, Kenneth Tripp, Niels Borgstein
Summary: The study demonstrates that the delayed-release formulation of linaclotide and MD-7246 show better improvement in abdominal pain compared to placebo. MD-7246 shows sustained but modest effects on pain relief, suggesting further investigation as a novel treatment for abdominal pain.
AMERICAN JOURNAL OF GASTROENTEROLOGY
(2021)
Article
Gastroenterology & Hepatology
Alejandro Velez Lopez, Amanda Waddell, Simona Antonacci, Daniel Castillo, Neha Santucci, Nicholas J. Ollberding, Emily M. Eshleman, Lee A. Denson, Theresa Alenghat
Summary: This study demonstrated that microbiota-derived butyrate can dampen human colonic responses to linaclotide in patient-derived colonoids, providing support for the incorporation of microbiota and metabolomic assessment to improve precision medicine for DGBI patients.
NEUROGASTROENTEROLOGY AND MOTILITY
(2023)
Review
Chemistry, Medicinal
Ernesto Fedele, Roberta Ricciarelli
Summary: cGMP, a classical second messenger, plays a key role in various physiological functions, particularly in the central nervous system for long-term potentiation. While preclinical studies show potential benefits for cognitive deficits in Alzheimer's disease, clinical studies are still inconclusive at this point.
Article
Veterinary Sciences
Satoshi Kameshima, Yuki Nakamura, Kenji Uehara, Tomoko Kodama, Hideyuki Yamawaki, Kotaro Nishi, Shozo Okano, Ryo Niijima, Yuya Kimura, Naoyuki Itoh
Summary: The aim of this study was to investigate the effects of riociguat on the contractility of the canine pulmonary artery and the hemodynamics of dogs with acute pulmonary hypertension (PH). It was found that riociguat can inhibit the elevation of pulmonary artery pressure in dogs with PH by increasing cGMP levels and reducing contraction induced by endothelin-1. Riociguat may be a novel and safe therapeutic agent for the treatment of PH in veterinary medicine.
VETERINARY SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Supachoke Mangmool, Ratchanee Duangrat, Warisara Parichatikanond, Hitoshi Kurose
Summary: Currently approved drugs for treating heart failure (HF) mainly target specific molecules involved in the regulation of the cardiac circulatory system. However, new drug classes with novel mechanisms have been introduced for HF intervention. SGLT2 inhibitors, in particular, have shown effectiveness in both reduced and preserved ejection fraction HF. Molecular pathways and clinical trials of emerging drug classes targeting cGMP signaling in HF treatment are summarized in this review.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Physiology
Shuxia Cao, Chengyong Han, Chunhua Xuan, Xiangdan Li, Jing Wen, Dongyuan Xu
Summary: This study explored the potential mechanisms of rapid atrial pacing (RAP) in regulating atrial natriuretic peptide (ANP) secretion. The results showed that NPR-A interacts with ANP to regulate particulate guanylate cyclase (PGC) expression and influence cyclic guanosine monophosphate (cGMP) expression during RAP, involving the Akt/GSK-3 beta signaling pathway.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Gastroenterology & Hepatology
Li Hua Peng, Jing Yuan Fang, Ning Dai, Xi Zhong Shen, You Lin Yang, Jing Sun, Yun Sheng Yang
Summary: Linaclotide (290 μg/d) was effective and well-tolerated in Chinese IBS-C patients, with a rapid onset of action.
JOURNAL OF DIGESTIVE DISEASES
(2022)