Review
Oncology
Ricardo D. Parrondo, Aneel Paulus, Sikander Ailawadhi
Summary: Monumental therapeutic advances have been made for the treatment of multiple myeloma in the past two decades. This paper reviews the available clinical data for Bcl-2 family protein inhibitors in the treatment of relapsed/refractory multiple myeloma, aiming to improve patient survival outcomes.
Article
Medicine, Research & Experimental
Elisabetta Valentini, Simona D'Aguanno, Marta Di Martile, Camilla Montesano, Virginia Ferraresi, Alexandros Patsilinakos, Manuela Sabatino, Lorenzo Antonini, Martina Chiacchiarini, Sergio Valente, Antonello Mai, Gianni Colotti, Rino Ragno, Daniela Trisciuoglio, Donatella Del Bufalo
Summary: Bcl-2 family anti-apoptotic proteins play a significant role in cancer, and finding new molecules targeting these proteins has therapeutic potential. Through virtual screening and experimental validation, IS20 and IS21 were identified as compounds that can inhibit the activity of Bcl-2 family proteins and have anti-proliferative and pro-apoptotic effects on various tumors.
Article
Biochemistry & Molecular Biology
Nirali Pandya, Mamta Singh, Reshma Rani, Vinit Kumar, Amit Kumar
Summary: Small molecule BiGh binds to bcl-2 G4 DNA structure with high affinity and selectivity, stabilizes the G4 motif, down-regulates bcl-2 gene transcription, induces cell apoptosis, and exhibits potential anti-cancer activity. This work provides a potential platform for the development of G4 stabilizers with drug-like properties.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2023)
Article
Cell Biology
Felix Wong, Satotaka Omori, Nina M. Donghia, Erica J. J. Zheng, James J. Collins
Summary: Researchers utilized a graph neural network platform to identify structurally diverse compounds with drug-like properties, and validated the in vivo activity of one compound in aged mice. These findings highlight the potential of deep learning in discovering anti-aging therapeutics.
Review
Pharmacology & Pharmacy
Rong Xiang, Zhengsen Yu, Yang Wang, Lili Wang, Shanshan Huo, Yanbai Li, Ruiying Liang, Qinghong Hao, Tianlei Ying, Yaning Gao, Fei Yu, Shibo Jiang
Summary: The COVID-19 pandemic has caused chaos worldwide, with vaccines in distribution but treatment methods lagging behind. Researchers are working hard to understand the virus and develop effective treatments.
ACTA PHARMACEUTICA SINICA B
(2022)
Article
Biochemistry & Molecular Biology
Bin Wang, Weiwei Feng, Jinan Wang, Yuanzhen Dong, Yanlong Liu, Yiyan Yao, Jianqing Zhang, Wei Shi, Limin Liu, Hongying Zhang, Xiangyi He, Xiayun Chang, Xiaojin Wang, Hongjiang Xu, Fei Liu, Jun Feng
Summary: A series of novel derivatives with acyl sulfonamide skeleton were designed, synthesized, and evaluated as Bcl-2 inhibitors in this study. Compound 24g showed efficient inhibition activity against RS4;11 cell line and improved selectivity for Bcl-2/Bcl-xL inhibitory effects, making it a promising candidate for novel therapeutics targeting Bcl-2 in cancer.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Jing-yi Zhou, Rui-rui Yang, Jie Chang, Jia Song, Zi-sheng Fan, Ying-hui Zhang, Cheng-hao Lu, Hua-liang Jiang, Ming-yue Zheng, Su-lin Zhang
Summary: This study describes the discovery and identification of a novel BCL-2 inhibitor, DC-B01, which targets the BH4 domain of BCL-2. The results indicate that DC-B01 induces cell apoptosis, inhibits tumor growth, and suppresses the transcriptional activity of c-Myc by disrupting the interaction between BCL-2 and c-Myc.
ACTA PHARMACOLOGICA SINICA
(2023)
Article
Multidisciplinary Sciences
Guodong Li, Chung-Nga Ko, Dan Li, Chao Yang, Wanhe Wang, Guan-Jun Yang, Carmelo Di Primo, Vincent Kam Wai Wong, Yaozu Xiang, Ligen Lin, Dik-Lung Ma, Chung-Hang Leung
Summary: This study reports the design and synthesis of a small molecule stabilizer of HIF-1 alpha, which promotes wound healing in diabetic patients according to experiments in mouse models. The compound accelerates wound closure in both normal and diabetic mice, with a greater effect observed in diabetic mice, indicating its potential as a therapeutic agent for diabetic wounds.
NATURE COMMUNICATIONS
(2021)
Article
Chemistry, Medicinal
Xuexin Feng, Ziqin Yan, Feilong Zhou, Jianfeng Lou, Xilin Lyu, Xuelian Ren, Ziyu Zeng, Chenglong Liu, Shiyan Zhang, Di Zhu, He Huang, Jinming Yang, Yujun Zhao
Summary: The study demonstrates that the FDA-approved drug Venetoclax induces apoptosis in cancer cells by blocking the interactions between BCL-2 and BH3-only proteins. However, the presence of anti-apoptotic protein BFL-1 leads to resistance to Venetoclax. The researchers identified and optimized a compound, named 12 (ZH97), as a covalent and selective inhibitor of BFL-1, which effectively induces apoptosis in BFL-1 overexpressing cancer cells.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Ibrahim H. Eissa, Radwan El-Haggar, Mohammed A. Dahab, Marwa F. Ahmed, Hazem A. Mahdy, Reem Alsantali, Alaa Elwan, Nicolas Masurier, Samar S. Fatahala
Summary: A novel series of compounds were designed and prepared, which showed potential antitumor activity and inhibitory effect on vascular endothelial growth factor receptor-2 (VEGFR-2), making them promising candidates for future anticancer therapy development.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Ginette S. Santiago-Sanchez, Ricardo Noriega-Rivera, Eliud Hernandez-O'Farrill, Fatma Valiyeva, Blanca Quinones-Diaz, Emilly S. Villodre, Bisrat G. Debeb, Andrea Rosado-Albacarys, Pablo E. Vivas-Mejia
Summary: Inflammatory Breast Cancer (IBC) is an aggressive form of breast cancer with high mortality rates, requiring targeted and effective therapies. Research suggests that LCN2 may be a promising target for IBC treatment, as silencing it reduces cell proliferation and invasion using siRNA and small molecule inhibitors. These findings demonstrate the potential of LCN2 as a therapeutic target in IBC.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Andrea Citarella, Angela Scala, Anna Piperno, Nicola Micale
Summary: The uncontrolled spread of COVID-19 caused by SARS-CoV-2 in 2020-2021 had devastating impacts on health, economy, and daily life globally. Despite approved vaccines, their long-term efficacy and safety are debated, prompting the search for new target-based drugs. Strategies targeting the coronavirus's main protease, M-pro, show promise for anti-coronavirus drug development.
Review
Biochemistry & Molecular Biology
Fan Yang, Zhigang Hu, Zhigang Guo
Summary: DNA damage repair is crucial for maintaining genomic stability and integrity, and FEN1 plays a critical role in this process. Abnormal expression or mutation of FEN1 is associated with various diseases, including cancers, making it a therapeutic target for cancer treatment. Small-molecule compounds targeting FEN1 have been developed and show promise in cancer therapy.
Article
Pharmacology & Pharmacy
Hong Zhang, Zongwei Guo, Yafei Guo, Ziqian Wang, Yao Tang, Ting Song, Zhichao Zhang
Summary: The research showed that the transfer of Bim between Bcl-2-like protein and Hsp70 underlies the crosstalk in mitochondrial apoptosis pathway, leading to apoptosis in cancer cell lines by inhibiting free Bim and facilitating oncogenic client AKT folding and activation.
BIOCHEMICAL PHARMACOLOGY
(2021)
Review
Medicine, General & Internal
Jianjing Lin, Shicheng Jia, Weifei Zhang, Mengyuan Nian, Peng Liu, Li Yang, Jianwei Zuo, Wei Li, Hui Zeng, Xintao Zhang
Summary: Osteoarthritis is a degenerative disease characterized by joint pain, caused by factors such as fibrosis, chapping, ulcers, and loss of articular cartilage. Traditional treatments only delay its progression, while small molecule inhibitors targeting proteins show promising effects in managing osteoarthritis. This review examines small molecule inhibitors targeting various proteins and discusses disease-modifying osteoarthritis drugs based on them, providing valuable insights for the treatment of osteoarthritis.
JOURNAL OF CLINICAL MEDICINE
(2023)