Article
Biochemistry & Molecular Biology
Radwan El-Haggar, Sherif F. Hammad, Reem I. Alsantali, Munira M. Alrooqi, Mahmoud A. El Hassab, Nicolas Masurier, Marwa F. Ahmed
Summary: The overexpression of EGFR is a driver mechanism in several human malignancies. EGFR inhibitors are the standard treatment for malignancies, but their efficacy is limited by resistance. A newly discovered compound has shown potential as an EGFR inhibitor, with activity against multiple cell lines and the ability to induce tumor cell cycle arrest and apoptosis.
BIOORGANIC CHEMISTRY
(2022)
Review
Chemistry, Multidisciplinary
Connor W. Coley
Summary: This review provides an overview of algorithmic approaches to defining and exploring chemical spaces for facilitating the process of molecular discovery. It highlights the potential roles of machine learning and the importance of considering synthetic feasibility.
TRENDS IN CHEMISTRY
(2021)
Review
Chemistry, Medicinal
Sahar S. Alghamdi, Rasha S. Suliman, Khlood Almutairi, Khawla Kahtani, Dimah Aljatli
Summary: Imidazole-containing compounds have shown promising therapeutic values in various disease conditions, including anti-cancer, anti-microbial, and anti-inflammatory activities. The electronic-rich characteristics of imidazole core scaffold enable it to readily bind with enzymes, proteins, and receptors, leading to potential mechanisms such as inhibition of COX-2 enzyme and protein kinase.
DRUG DESIGN DEVELOPMENT AND THERAPY
(2021)
Article
Chemistry, Medicinal
Zhicheng Xie, Caigui Xiang, Xin Li, Chen Fan, Taiwen Chen, Moting Liu, Yanjie Ma, Fang Bai, Wei Tang, Youhong Hu
Summary: This study reported a novel orally bioavailable anti-allergic agent that showed potent inhibition of mast cell degranulation, cell signaling regulation, and efficacy in murine models of allergic inflammation. The compound may serve as a valuable lead for future anti-allergic drug discovery.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Chemistry, Medicinal
Kashif Haider, Sara Rehman, Ankita Pathak, Abul K. Najmi, Mohammad S. Yar
Summary: Targeted therapy is crucial in cancer treatment, overcoming drawbacks of conventional therapy. Heterocyclic derivatives have gained attention as cytotoxic agents, with benzothiazole being explored for its therapeutic potential. Benzothiazole-based derivatives have emerged as potent inhibitors of enzymes, with some already in clinical trials. This review highlights recent advancements in benzothiazole-based derivatives as potent anticancer agents.
ARCHIV DER PHARMAZIE
(2021)
Article
Chemistry, Medicinal
Aurelien Beato, Anthonin Gori, Benjamin Boucherle, Marine Peuchmaur, Romain Haudecoeur
Summary: Natural beta-carboline alkaloids show similarities with neurotransmitters, which can be exploited to design drugs for Alzheimer's disease therapy. Current research focuses on investigating different hypotheses related to AD, with the beta-carboline scaffold identified as a powerful tool for interacting with a wide range of AD-related targets to design multitarget-directed ligands.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Pharmacology & Pharmacy
Rajashri R. Naik, Ashok K. Shakya
Summary: Protein kinases transfer phosphate to proteins, modifying their structure. The human genome contains approximately 538 kinases, which play a crucial role in various cellular processes. Dysregulation of kinases is associated with the development of diseases, particularly cancer. Understanding the mechanisms and roles of kinases has led to the development of kinase inhibitors with promising clinical benefits.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Siddharth Yadav, Shahzaib Ahamad, Dinesh Gupta, Puniti Mathur
Summary: The study aims to optimize Silmitasertib, develop pharmacophore models, and design unique scaffolds to modulate Protein kinase CK2 (CK2). Candidates structurally similar to Silmitasertib were identified through bioisostere replacement and docking approaches. Molecular dynamics simulations were used to evaluate the interaction and stability of promising candidates. Ligand-based and structure-based pharmacophore models were merged to build a hybrid hypothesis, which was validated and used to screen for favorable chemical features in kinase inhibitors. Novel scaffolds with the potential to modulate CK2 were identified through de-novo scaffold design.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Biochemistry & Molecular Biology
Shenxin Zeng, Ming Zeng, Shuai Yuan, Liuxun He, Yuyuan Jin, Jiandong Huang, Manxuan Zhang, Menghan Yang, Youlu Pan, Zunyuan Wang, Yinqiao Chen, Xiangwei Xu, Wenhai Huang
Summary: This study describes the discovery and structure-activity relationship (SAR) of potent HPK1 inhibitors based on the 2,4-disubstituted pyrimidine scaffold. The compound HMC-H8 was identified as a highly selective and potent inhibitor of HPK1, with additional effects on p-SLP 76 inhibition and promotion of IL-2 release and INF-gamma production. It also exhibited acceptable metabolic stability, low CYP450 inhibition, and good oral bioavailability in preclinical studies.
BIOORGANIC CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Mbilo Misehe, Marika Matousova, Alexandra Dvorakova, Kamil Hercik, Krystof Skach, Dominika Chalupska, Milan Dejmek, Michal Sala, Miroslav Hajek, Evzen Boura, Helena Mertlikova-Kaisrova, Radim Nencka
Summary: In this study, novel quinazoline-based derivatives were developed and extensive modifications were made to positions 6 and 7 of the central core to investigate their inhibitory activity and selectivity against RIPK2 and RIPK3. The results showed the presence of multiple potent and selective RIPK2 and dual RIPK2/3 inhibitors, as well as outstanding specificity profiles against other kinases. This knowledge can be utilized to develop highly potent and selective tools against RIPK2 and RIPK3.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Chemistry, Multidisciplinary
Roberta Listro, Giacomo Rossino, Federica Piaggi, Falilat Folasade Sonekan, Daniela Rossi, Pasquale Linciano, Simona Collina
Summary: This review highlights the importance of the urea moiety in the field of anticancer drugs, with a special focus on its application in kinase inhibitors. Urea has unique drug-target interaction networks, physicochemical properties that are useful for tuning the druggability of new chemical entities, and versatile structure and synthetic flexibility.
FRONTIERS IN CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Christian Borgo, Luca Cesaro, Tsuyoshi Hirota, Keiko Kuwata, Claudio D'Amore, Thomas Ruppert, Renata Blatnik, Mauro Salvi, Lorenzo A. Pinna
Summary: CK2, a protein kinase with pleiotropic functions, is implicated in global human pathologies, particularly cancer. Selective inhibitors like CX4945 and GO289 show promise in controlling the CK2-dependent phosphoproteome.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Ezra Y. Rosen, Helen H. Won, Youyun Zheng, Emiliano Cocco, Duygu Selcuklu, Yixiao Gong, Noah D. Friedman, Ino de Bruijn, Onur Sumer, Craig M. Bielski, Casey Savin, Caitlin Bourque, Christina Falcon, Nikeysha Clarke, Xiaohong Jing, Fanli Meng, Catherine Zimel, Sophie Shifman, Srusthi Kittane, Fan Wu, Marc Ladanyi, Kevin Ebata, Jennifer Kherani, Barbara J. Brandhuber, James Fagin, Eric J. Sherman, Natasha Rekhtman, Michael F. Berger, Maurizio Scaltriti, David M. Hyman, Barry S. Taylor, Alexander Drilon
Summary: The study has established the efficacy of the highly selective RET inhibitor selpercatinib in patients with RET-driven cancers, but also discovered potential mechanisms of resistance, revealing the complexity of acquired resistance and suggesting the importance of combination therapy targeting alternative pathways in overcoming resistance.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Zia ur Rehman, Asim Najmi
Summary: This study identifies three potential EGFR kinase inhibitors through virtual screening and confirms their activity through molecular dynamics simulation and steered MD studies.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Chemistry, Medicinal
Anne-Sophie Castanet, Mohamed S. Nafie, Sara A. Said, Reem K. Arafa
Summary: This research focuses on the design and synthesis of a new PIM-1 kinase targeting compound, and investigates its potential as an anti-cancer agent through in vitro and in vivo studies. The results demonstrate that compound 10f exhibits strong cytotoxicity against prostate cancer cells, inhibits PIM-1 kinase activity, and has antioxidant and apoptosis-inducing effects. Moreover, 10f shows significant anti-tumor activity in a mouse model. Therefore, compound 10f holds promise as a lead compound for prostate cancer treatment.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)