Review
Oncology
Rossella Elisei, Enrique Grande, Michael C. Kreissl, Sophie Leboulleux, Tarun Puri, Nicolas Fasnacht, Jaume Capdevila
Summary: The incidence of thyroid cancer is increasing globally, with Europe ranking second in disease burden after Asia. Over the past few decades, research has identified key molecular pathways and targetable kinases/drivers for each histologic subtype of thyroid cancer. Newer and selective RET inhibitors, such as selpercatinib and pralsetinib, have shown promising efficacy and favorable toxicity profiles in clinical trials for the treatment of RET-driven advanced thyroid cancer. Genetic testing is crucial to identify RET alterations and determine the optimal treatment approach.
FRONTIERS IN ONCOLOGY
(2023)
Review
Pharmacology & Pharmacy
Pietro Locantore, Roberto Novizio, Andrea Corsello, Rosa Maria Paragliola, Alfredo Pontecorvi, Salvatore Maria Corsello
Summary: Pralsetinib, a highly selective RET inhibitor, has shown higher potency and lower toxicity compared to traditional MKIs in the treatment of RET-mutated thyroid cancer. Clinical validation studies have demonstrated a better overall response rate with pralsetinib, pointing towards its potential as a promising treatment option for patients with this specific mutation. Future clinical trials and data analysis are warranted to further understand the full pharmacological profile and clinical benefits of pralsetinib.
EXPERT OPINION ON DRUG DISCOVERY
(2022)
Article
Chemistry, Medicinal
Zhibo Luo, Lingli Wang, Zhifei Fu, Bin Shuai, Miaorong Luo, Guoping Hu, Jian Chen, Jikui Sun, Jiansong Wang, Jian Li, Shuhui Chen, Yang Zhang
Summary: The researchers designed and synthesized a series of novel RET inhibitors based on BLU-667 structure, with compound 9 identified as a potent selective RET inhibitor showing improved drug-like properties. Compound 9 exhibited good inhibitory effects on mutant RET and effectively suppressed the proliferation of cells transfected with KIF5B-RET fusion gene. It also displayed fewer 'off-target' effects compared to BLU-667, making it a promising lead for discovering RET-directed therapeutic agents.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2021)
Review
Pharmacology & Pharmacy
Sareshma Sudhesh Dev, Syafiq Asnawi Zainal Abidin, Reyhaneh Farghadani, Iekhsan Othman, Rakesh Naidu
Summary: Receptor tyrosine kinases (RTKs) are crucial cell-surface proteins that regulate essential cellular processes, with alterations in them playing a key role in cancer progression. Curcumin, as an attractive anti-cancer agent, exhibits potent effects by inhibiting RTKs and downstream signaling pathways.
FRONTIERS IN PHARMACOLOGY
(2021)
Review
Oncology
Kalpana K. Bhanumathy, Amrutha Balagopal, Frederick S. Vizeacoumar, Franco J. Vizeacoumar, Andrew Freywald, Vincenzo Giambra
Summary: Protein phosphorylation is a key regulatory mechanism controlling cellular responses, catalysed by members of the protein kinase superfamily. Tyrosine kinases have been extensively studied for their roles in human malignancies, leading to the development of targeted therapies. Various tyrosine kinases, both receptor and nonreceptor types, play critical roles in the pathogenesis and drug resistance of leukemia, highlighting their potential as therapeutic targets.
Review
Chemistry, Analytical
Juan Gao, Jingyi Jian, Zhengjin Jiang, Ann Van Schepdael
Summary: Tyrosine kinases have been extensively studied as drug targets due to their regulation of cellular processes. The deregulation of tyrosine kinases plays a key role in the pathophysiology of various diseases. Several techniques, including traditional binding assays and high-throughput screening methods, have been developed to discover new tyrosine kinase inhibitors. This review provides insights into the different assay methods for the exploration of novel tyrosine kinase inhibitors.
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
(2023)
Article
Oncology
Antonio Passaro, Giuseppe Lo Russo, Francesco Passiglia, Manolo D'Arcangelo, Andrea Sbrana, Marco Russano, Laura Bonanno, Raffaele Giusti, Giulio Metro, Federica Bertolini, Salvatore Grisanti, Annamaria Carta, Fabiana Cecere, Michele Montrone, Giacomo Massa, Fabiana Perrone, Francesca Simionato, Giorgia Guaitoli, Vieri Scotti, Carlo Genova, Antonio Lugini, Lucia Bonomi, Ilaria Attili, Filippo de Marinis
Summary: In the real-world setting, pralsetinib demonstrated durable systemic activity and intracranial response in patients with RET-fusion positive NSCLC. The toxicity profile of pralsetinib was consistent with previous reports.
Article
Biochemistry & Molecular Biology
Pearly Shuyi Ng, Klement Foo, Sandra Sim, Gang Wang, Chuhui Huang, Li Hong Tan, Anders Poulsen, Boping Liu, Doris Hui Ying Tee, Nur Huda Binte Ahmad, Sifang Wang, Zhiyuan Ke, May Ann Lee, Zekui P. Kwek, Joma Joy, Jothi Anantharajan, Nithya Baburajendran, Vishal Pendharkar, Vithya Manoharan, Susmitha Vuddagiri, Kanda Sangthongpitag, Jeffrey Hill, Thomas H. Keller, Alvin W. Hung
Summary: This study identified a new indazole-based AXL inhibitor through a fragment-based lead discovery approach, providing a suitable starting point for further optimization efforts.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Article
Endocrinology & Metabolism
Rossella Elisei, Raffaele Ciampi, Antonio Matrone, Alessandro Prete, Carla Gambale, Teresa Ramone, George Simeakis, Gabriele Materazzi, Liborio Torregrossa, Clara Ugolini, Cristina Romei
Summary: RET indels are not uncommon in MTC patients and are associated with aggressive disease. Two patients with RET indels showed partial response to treatment with Selpercatinib.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2022)
Article
Chemistry, Multidisciplinary
Meng-di Dai, Yue-liang Wang, Jun Fan, Yang Dai, Yin-chun Ji, Yi-ming Sun, Xia Peng, Lan-lan Li, Yu-ming Wang, Wen-hu Duan, Jian Ding, Jing Ai
Summary: DW14383 is a promising selective irreversible pan-FGFR inhibitor with pan-tumor spectrum potential in FGFR1-4 aberrant cancers, which has the potential to overcome compensatory activation among FGFR1-4.
ACTA PHARMACOLOGICA SINICA
(2021)
Article
Oncology
T. Cascone, R. L. Sacks, I. M. Subbiah, N. Drobnitzky, S. A. Piha-Paul, D. S. Hong, K. R. Hess, B. Amini, T. Bhatt, S. Fu, A. Naing, F. Janku, D. Karp, G. S. Falchook, A. P. Conley, S. Sherman, F. Meric-Bernstam, A. J. Ryan, J. Heymach, V Subbiah
Summary: The combination therapy of VAN + EV shows promising antitumor activity in advanced solid cancers, with manageable toxicities. Further studies are needed to explore its efficacy in tumors with RET pathway aberrations.
Article
Biochemistry & Molecular Biology
Esther Martinez-Martinez, Regine Toelle, Julia Donauer, Christine Gretzmeier, Leena Bruckner-Tuderman, Joern Dengjel
Summary: Loss of collagen VII in recessive dystrophic epidermolysis bullosa (RDEB) affects PDGFR signaling and intracellular pathways, leading to impaired wound healing. Elevated TGF beta signaling in RDEB contributes to attenuated response to growth factors, resulting in impaired dermal wound healing.
Article
Oncology
Matteo Repetto, Edoardo Crimini, Liliana Ascione, Luca Boscolo Bielo, Carmen Belli, Giuseppe Curigliano
Summary: The study aims to predict potential mutations inducing resistance to TPX-0046, to overcome resistance to FDA approved RET inhibitors. The findings suggest that different mutations have different effects on TPX-0046 binding, which is important for the development of second and third generation RET inhibitors and clinical trial design.
INVESTIGATIONAL NEW DRUGS
(2022)
Article
Biochemistry & Molecular Biology
Masoumeh Divar, Najmeh Edraki, Tahereh Damghani, Fatemeh Moosavi, Maryam Mohabbati, Alireza Alipour, Somayeh Pirhadi, Luciano Saso, Soghra Khabnadideh, Omidreza Firuzi
Summary: Despite advances in therapeutic strategies, cancer remains a leading cause of death. This study synthesized a new series of spiro[indoline-3,2'-quinazoline]-2,4'(3'H)-dione derivatives and evaluated their potential as kinase inhibitors with anti-cancer effects. The most promising compounds exhibited anti-proliferative activity against various cancer cell lines and altered the distribution of cells in the cell cycle. FLT3 kinase was identified as the primary target of these compounds. Compound 5f showed potent inhibitory activity against wild-type FLT3 and its mutant, D835Y. Docking and simulation studies revealed the important interactions of compound 5f with FLT3. These findings suggest that these spiroindoline quinazolinedione compounds could be promising candidates for novel anticancer drugs.
BIOORGANIC & MEDICINAL CHEMISTRY
(2023)
Review
Endocrinology & Metabolism
Artak Labadzhyan, Shlomo Melmed
Summary: Molecular therapeutic targets in growth hormone-secreting adenomas have potential for drug development, including surface receptors recognized by approved drugs and markers for new drug candidates. Current medical therapies control the disease in most patients but the degree of control varies and is related to disease aggressiveness and tumor factors. Understanding the mechanisms behind these molecular markers and their relationship to outcomes holds promise for expanding treatment options and personalized approaches.
FRONTIERS IN ENDOCRINOLOGY
(2022)
