Article
Chemistry, Medicinal
Jing Yu, Chao Zhang, Chun Song
Summary: In the past few decades, the development of Hsp90 inhibitors for cancer treatment has been ongoing. However, many compounds evaluated in clinical trials were not approved by the FDA due to toxic effects and lack of efficacy. Insufficient isoform selectivity has been identified as one of the reasons for these failures. Therefore, the development of isoform-specific Hsp90 inhibitors could lead to significant progress in finding therapeutic agents for cancer and other diseases. This article provides a summary of classic pan-inhibitors of Hsp90 and discusses the design strategies used in drug discovery. It also summarizes current isoform-specific Hsp90 inhibitors, including their discovery processes and potential indications.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Yujiao Wei, Yanting Tang, Yunyun Zhou, Yuyu Yang, Yetong Cui, Xuan Wang, Yubo Wang, Yulin Liu, Ning Liu, Qianqian Wang, Chong Li, Hao Ruan, Honggang Zhou, Mingming Wei, Guang Yang, Cheng Yang
Summary: The study identified a novel lead compound 36 with significant inhibitory effects against FGFR (1-3) and demonstrated low toxicity and adequate pharmacokinetic properties. Compound 36 also showed significant anti-proliferation effects against cancer cell lines NCI-H1581 and SNU-16, making it a potential drug candidate under validation.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Oncology
Marie-Pierre Sunyach, Nicolas Penel, Laure Montane, Philippe A. Cassier, Abel Cordoba Largo, Paul Sargos, Ellen Blanc, David Perol, Jean-Yves Blay
Summary: This French study assessed the feasibility and safety of continuous administration of sunitinib with concomitant radiotherapy in inoperable non-GIST sarcomas patients. The combination treatment was found to be feasible and effective, but further investigations on combinations with more recent multikinase inhibitors and radiotherapy are needed.
RADIOTHERAPY AND ONCOLOGY
(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
Meghan J. Mooradian, James M. Cleary, Anita Giobbie-Hurder, Lancia N. F. Darville, Aparna Parikh, Elizabeth I. Buchbinder, Justine V. Cohen, Donald P. Lawrence, Geoffrey I. Shapiro, Harold Keer, Helen X. X. Chen, Susan Percy Ivy, Keiran S. M. Smalley, John M. Koomen, Ryan J. Sullivan
Summary: This study showed that the combination of HSP90 inhibitor AT13387 with dabrafenib and trametinib was safe and led to modest disease control in heavily pretreated patients with BRAF V600E/K-mutant solid tumors. Further research is needed to identify tumor types and resistance mechanisms that are most sensitive to this approach.
Article
Multidisciplinary Sciences
R. Charles Coombes, Sacha Howell, Simon R. Lord, Laura Kenny, Janine Mansi, Zahi Mitri, Carlo Palmieri, Linnea I. Chap, Paul Richards, William Gradishar, Sagar Sardesai, Jason Melear, Joyce O'Shaughnessy, Patrick Ward, Pavani Chalasani, Tobias Arkenau, Richard D. Baird, Rinath Jeselsohn, Simak Ali, Glen Clack, Ashwani Bahl, Stuart McIntosh, Matthew G. Krebs
Summary: This study reports the clinical trial results of samuraciclib as an anti-cancer treatment, showing its clinical activity in patients with triple negative breast cancer and HR+/HER2- breast cancer.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Medicinal
Shihe Hu, Yu Liu, Jiye Ma, Weijie Ding, Hua Chen, Haifang Jiang, Hongxing Chen, Song Wei, Yonggao Liu, Qiaomei Jin, Haoliang Yuan, Libo Yan
Summary: Under the guidance of molecular docking, we discovered a series of novel quinolone-based covalent pan-FGFR inhibitors, with the representative inhibitor I-5 exhibiting nanomolar activity against FGFR1-4 and effectively suppressing the proliferation of Huh-7 and Hep3B liver cells.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Oncology
Siddhartha Laskar, Shwetabh Sinha, Abhishek Chatterjee, Nehal Khanna, Jifmi Jose Manjali, Ajay Puri, Ashish Gulia, Prakash Nayak, Tushar Vora, Girish Chinnaswamy, Maya Prasad, Jyoti Bajpai, Shashikant Juvekar, Subhash Desai, Amit Janu, Venkatesh Rangarajan, Nilendu Purandare, Sneha Shah, Bharat Rekhi, Nirmala Jambhekar, Mary Ann Muckaden, Purna Kurkure
Summary: Radiation therapy dose escalation can improve local control in surgically unresectable Ewing sarcoma/primitive neuroectodermal tumor patients, with good functional outcomes and without a significant increase in toxic effects.
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
(2022)
Article
Gastroenterology & Hepatology
Amy Yu, Nghiem B. Ha, Bingyan Shi, Yao-Wen Cheng, Uma Mahadevan, Kendall R. Beck
Summary: This study aimed to evaluate predictors and outcomes of disease activity after tofacitinib dose de-escalation in patients with ulcerative colitis. Results showed that approximately 56% of patients experienced disease activity-related events within 12 months after dose de-escalation. Factors associated with disease events included an induction course of less than 16 weeks and active endoscopic disease within 6 months after initiation.
CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
(2023)
Article
Pharmacology & Pharmacy
Ewoud-Jan van Hoogdalem, Mattheus (Thijs) van Iersel, Erica Winter, John Constant, Martin Kappler
Summary: This research introduces a pharmacology-guided rule-based adaptive dose escalation design for first-in-human studies, which has been demonstrated to effectively utilize participants in early clinical drug evaluation without compromising safety through retrospective evaluation and trial simulations.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2021)
Article
Oncology
Her-Shyong Shiah, Nai-Jung Chiang, Chia-Chi Lin, Chia-Jui Yen, Hui-Jen Tsai, Shang-Yin Wu, Wu-Chou Su, Kwang-Yu Chang, Ching-Chiung Wang, Jang-Yang Chang, Li-Tzong Chen
Summary: The novel microtubule inhibitor SCB01A has vascular disrupting activity and is safe and tolerable in patients with solid tumors, with a maximum tolerated dose of 24 mg/m(2) every 21 days and a half-life of approximately 2.5 hours. Treatment-related adverse events included anemia, nausea, vomiting, and some patients experienced neurotoxicity.
Article
Oncology
Soo Jin Park, Suk-Joon Chang, Dong Hoon Suh, Tae Wook Kong, Heekyoung Song, Tae Hun Kim, Jae-Weon Kim, Hee Seung Kim, Sung-Jong Lee
Summary: This study evaluates the safety and tolerability of PHI-101 in platinum-resistant recurrent ovarian cancer. By determining the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of PHI-101, this study aims to find the recommended dose for further clinical trials. The study may contribute to developing a new combination regimen for the treatment of ovarian cancer.
Article
Oncology
Matthias Fischer, Lucas Moreno, David S. Ziegler, Lynley Marshall, C. Michel Zwaan, Meredith S. Irwin, Michela Casanova, Constantino Sabado, Beate Wulff, Mario Stegert, Luojun Wang, Felipe K. Hurtado, Fabrice Branle, Birgit Geoerger, Johannes H. Schulte
Summary: This study investigated the safety, pharmacokinetics, and efficacy of ceritinib in paediatric patients with ALK-positive malignancies. Results showed that the recommended dose for paediatric patients with ALK-positive malignancies is 500 mg/m(2) of ceritinib, which demonstrated promising antitumor activity.
Article
Oncology
Amita Patnaik, Erika Hamilton, Yan Xing, Drew W. Rasco, Lon Smith, Ya-Li Lee, Steven Fang, Jiao Wei, Ai-Min Hui
Summary: This study examines the safety and antitumor efficacy of a novel CDK4/6 inhibitor, FCN-437c, in patients with advanced solid tumors. The results show promising signs of durable tumor response and disease control. Further research is needed to investigate the safety and efficacy of FCN-437c.
Article
Medicine, General & Internal
Xuan Wang, Zhiguo Luo, Jing Chen, Yu Chen, Dongmei Ji, Li Fan, Ling Chen, Qian Zhao, Pei Hu, Peng Sun, Zhongwei Jia, Jun Guo, Lu Si
Summary: HL-085 demonstrates acceptable tolerability and significant clinical activity in patients with advanced melanoma harboring NRAS mutations.