Article
Chemistry, Organic
Keisuke Mitsui, Maria E. K. Lie, Naoki Saito, Koichi Fujiwara, Mizuki Watanabe, Petrine Wellendorph, Satoshi Shuto
Summary: Novel gamma-aminobutyric acid (GABA) analogues with different backbones were designed based on the analysis of the bioactive form of a previous inhibitor. These compounds were synthesized using ring-closing metathesis and compound 4 showed selective low micromolar potency.
Article
Chemistry, Medicinal
Barbara Czako, Yuting Sun, Timothy McAfoos, Jason B. Cross, Paul G. Leonard, Jason P. Burke, Christopher L. Carroll, Ningping Feng, Angela L. Harris, Yongying Jiang, Zhijun Kang, Jeffrey J. Kovacs, Pijus Mandal, Brooke A. Meyers, Faika Mseeh, Connor A. Parker, Simon S. Yu, Christopher C. Williams, Qi Wu, Maria Emilia Di Francesco, Giulio Draetta, Timothy Heffernan, Joseph R. Marszalek, Nancy E. Kohl, Philip Jones
Summary: The search for potent compounds interfering with the function of SHP2 led to the discovery of a series of pyrimidinone compounds with high potency and narrow hERG window in humans, showing potential for targeted therapies in cancers driven by RTK and KRAS mutations.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Carine M. Abdelmalek, Zexi Hu, Thales Kronenberger, Jenni Kublbeck, Franziska J. M. Kinnen, Salma S. Hesse, Afsin Malik, Mark Kudolo, Raimund Niess, Matthias Gehringer, Lars Zender, Paula A. Witt-Enderby, Darius P. Zlotos, Stefan A. Laufer
Summary: Anticancer drug conjugates that simultaneously target two receptors may overcome the limitations of current cancer treatments. A series of compounds connecting tamoxifen or endoxifen with the EGFR-inhibitor gefitinib exhibit potent anticancer activity in breast cancer cells.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Soumava Santra, Sandhya Kortagere, Seenuvasan Vedachalam, Sanjib Gogoi, Tamara Antonio, Maarten E. A. Reith, Aloke K. Dutta
Summary: The study revealed a significant influence from the alteration of the stereochemistry of the hydroxyl group on the pyran ring of D-473 on transporters affinities, indicating stereospecific preference for interaction. Furthermore, novel compounds such as D-528 and D-529 were identified as some of the most potent dopamine-norepinephrine reuptake inhibitors known to-date. Computational analysis found that the nature of interactions from molecular docking experiments correlated well with the affinities of the compounds for the transporters.
ACS CHEMICAL NEUROSCIENCE
(2021)
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
Chemistry, Physical
M. Maria Julie, T. Prabhu, E. Elamuruguporchelvi, Fazilath Basha Asif, S. Muthu, Ahmad Irfan
Summary: This study utilized Gaussian 16W density functional theory to investigate the structural, wave functional, and electronic properties of a specific compound. Various properties such as optimized geometrical properties, wave functional characteristics, band gap energies, reactive sites, excited energies, and molecular interactions were analyzed using different computational methods. Spectroscopic wave numbers were predicted and biological activities were explored through molecular docking study.
JOURNAL OF MOLECULAR LIQUIDS
(2021)
Article
Chemistry, Physical
Pilei Si, Haijun Chen, Jiquan Liu, Enzhao Zhang, Chengzhen Li, Jiaojiao Gu, Ruoyan Wang, Wentao Li
Summary: In this study, a potent BRD4 inhibitor, 10-HCPT, was identified for the treatment of triple-negative breast cancer (TNBC). The results showed that 10-HCPT can inhibit the growth of TNBC cells by binding to BRD4 and inducing apoptosis. The study also provided new insights into the potential use of 10-HCPT as a therapy for TNBC.
JOURNAL OF MOLECULAR STRUCTURE
(2022)
Article
Multidisciplinary Sciences
Saharish Khaliq, Mohsin Abbas Khan, Irshad Ahmad, Imtiaz Ahmad, Javed Ahmed, Farhat Ullah
Summary: The goal of this work was to create structural analogues of a beta lactam antibiotic to combat bacterial resistant strains. The spectroscopic study on compounds M1-8 using FTIR, H-1 NMR, C-13 NMR, and CHNS analyses showed that two molecules, M-2 and M-3, had stronger antibacterial activity. The findings are significant for the search for effective drugs against antibiotic-resistant bacteria.
Article
Biochemistry & Molecular Biology
Xianlian Wang, Yongmei Xu, Zaiwei Zong, Jinna Cai, Chunlin Chen, Qingwei Zhang, Xun Sun, Jianqi Li
Summary: A series of 5-methyl-2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole derivatives were synthesized and evaluated for their potential as a novel potent potassium-competitive acid blocker (P-CAB) agent. Compound 3-((3-(2-fluorophenyl)-5-methyl-5,6-dihydropyrrolo[3,4-c]pyrazol-2(4H)-yl)methyl)-[1,1'-biphenyl]-3-carboxamide showed promising inhibitory activity and potential as a P-CAB agent for further investigation.
BIOORGANIC & MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Byung-Nam Kang, Hong-Jun Kang, Sunjoo Kim, Jungwoo Lee, Jinwoo Lee, Hee-Jin Jeong, Seeun Jeon, Youngdo Shin, Cheolhwan Yoon, Cheolkyu Han, Jeongbeob Seo, Jaesook Yun
Summary: Specific inhibition of ALK5 can control the development of cancers and fibrotic diseases effectively. In this study, a potential clinical candidate, N-(3-fluorobenzyl)-4-(1-(methyl-d3)-1H-indazol-5-yl)-5-(6-methylpyridin-2-yl)-1H-imidazol-2-amine (11), was synthesized by incorporating deuterium at potential metabolic soft spots and identified as an ALK5 inhibitor.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Cell Biology
Yusuke Shiraishi, Tomohiko Maehama, Miki Nishio, Junji Otani, Hiroki Hikasa, Tak Wah Mak, Takehiko Sasaki, Teruki Honma, Yasumitsu Kondoh, Hiroyuki Osada, Minoru Yoshida, Masato Fujisawa, Akira Suzuki
Summary: DMPCA has been found to suppress the viability of BlC cells by inducing the phosphorylation of LATS1 and YAP1/TAZ, showing potential anti-tumor effects.
Article
Chemistry, Medicinal
Jinxin Che, Xiaoyang Dai, Jian Gao, Haichao Sheng, Wenhu Zhan, Yang Lu, Dan Li, Zizheng Gao, Zegao Jin, Binhui Chen, Peihua Luo, Bo Yang, Yongzhou Hu, Qiaojun He, Qinjie Weng, Xiaowu Dong
Summary: Inhibiting Akt2 isozyme may lead to keratinocyte apoptosis, driving the search for new selective Akt inhibitors with improved cutaneous safety. After optimization, Hu7691 shows promising selectivity, low apoptosis induction in keratinocytes, and excellent anticancer cell proliferation potency, leading to its approval by NMPA for clinical trials.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Organic
Meng Xu, Shenyuan Gao, Yuanxu Zeng, Anhui Gao, Lixin Gao, Lei Xu, Yubo Zhou, Jianrong Gao, Qing Ye, Jia Li
Summary: A series of novel maleimide compounds were synthesized and evaluated for their inhibitory activity against mutant isocitrate dehydrogenase-1 (R132H), with compound 9b showing the most promising results. It was found that compound 9b could significantly inhibit the production of 2-HG.
CHINESE JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Taehun Song, Moonsub Lee, Inhwan Bae, Joo-Yun Byun, Young Gil Ahn, Young Hoon Kim, Young-Jin Chun
Summary: Cyclin-dependent kinase (CDK) 9 is a key regulator in transcription process and a potential target for cancer therapy. Compound 8 has been shown to exhibit potent CDK9 inhibitory activity and potential antitumor efficacy in mouse models, holding promise as a highly potent CDK9 inhibitor for anticancer approaches.
BULLETIN OF THE KOREAN CHEMICAL SOCIETY
(2021)
Article
Medicine, Research & Experimental
Shan Xu, Xin Sun, Leixuan Luo, Yang Yang, Qiuyan Guo, Sheng Tang, Zhiyan Jiang, Yuzhen Li, Jiaqian Han, Wenhui Gan, Feiyi Yang, Xuan Zhang, Yijun Liu, Chuanchuan Sun, Jie He, Meng Liu, Daiying Zuo, Wufu Zhu, Yingliang Wu
Summary: Breast cancer has become the most commonly diagnosed cancer and there is an urgent need for effective therapeutic drugs. In this study, a novel drug XS-2 was designed and synthesized, showing potent anti-tumor activity against breast cancer cells, particularly triple-negative breast cancer (TNBC). XS-2 exhibited strong inhibitory effects on cancer cells both in vitro and in vivo, with low toxicity. Furthermore, XS-2 was found to inhibit cell invasion and migration. These findings suggest that XS-2 has the potential to be developed as a high-efficiency and low-toxicity therapeutic drug for TNBC.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Biochemistry & Molecular Biology
Fabrizio Micheli, Andrea Bernardelli, Federica Bianchi, Simone Braggio, Laura Castelletti, Palmina Cavallini, Paolo Cavanni, Susanna Cremonesi, Michele Dal Cin, Aldo Feriani, Beatrice Oliosi, Teresa Semeraro, Luca Tarsi, Silvia Tomelleri, Andrea Wong, Filippo Visentini, Laura Zonzini, Christian Heidbreder
BIOORGANIC & MEDICINAL CHEMISTRY
(2016)
Article
Chemistry, Medicinal
Fabrizio Micheli, Susanna Cremonesi, Teresa Semeraro, Luca Tarsi, Silvia Tomelleri, Paolo Cavanni, Beatrice Oliosi, Elisabetta Perdona, Anna Sava, Laura Zonzini, Aldo Feriani, Simone Braggio, Christian Heidbreder
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2016)
Article
Chemistry, Medicinal
Fabrizio Micheli, Alessia Bacchi, Simone Braggio, Laura Castelletti, Palmina Cavallini, Paolo Cavanni, Susanna Cremonesi, Michele Dal Cin, Aldo Feriani, Sylvie Gehanne, Mahmud Kajbaf, Luciano Marchio, Selena Nola, Beatrice Oliosi, Annalisa Pellacani, Elisabetfa Perdona, Anna Sava, Teresa Semeraro, Luca Tarsi, Silvia Tomelleri, Andrea Wong, Filippo Visentini, Laura Zonzini, Christian Heidbreder
JOURNAL OF MEDICINAL CHEMISTRY
(2016)
Article
Biochemistry & Molecular Biology
Fabrizio Micheli, Paolo Cavanni, Michela Bettati, Giorgio Bonanomi, Romano Di Fabio, Elettra Fazzolari, Carla Marchioro, Maja Roscic, Luca Tarsi, Filippo Visentini, Laura Zonzini, Angela Worby
BIOORGANIC & MEDICINAL CHEMISTRY
(2011)
Article
Biochemistry & Molecular Biology
Romano Di Fabio, Giuseppe Alvaro, Simone Braggio, Renzo Carletti, Philip A. Gerrard, Cristiana Griffante, Carla Marchioro, Alfonso Pozzan, Sergio Melotto, Alessandro Poffe, Laura Piccoli, Emiliangelo Ratti, Elvira Tranquillini, Michael Trower, Simone Spada, Mauro Corsi
BIOORGANIC & MEDICINAL CHEMISTRY
(2013)
Article
Chemistry, Medicinal
Romano Di Fabio, Annalisa Pellacani, Stefania Faedo, Adelheid Roth, Laura Piccoli, Philip Gerrard, Rod A. Porter, Christopher N. Johnson, Kevin Thewlis, Daniele Donati, Luigi Stasi, Simone Spada, Geoffrey Stemp, David Nash, Clive Branch, Leanda Kindon, Mario Massagrande, Alessandro Poffe, Simone Braggio, Elisabetta Chiarparin, Carla Marchioro, Emiliangelo Ratti, Mauro Corsi
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2011)
Article
Chemistry, Medicinal
Francesca Spyrakis, Barbara Cellini, Stefano Bruno, Paolo Benedetti, Emanuele Carosati, Gabriele Cruciani, Fabrizio Micheli, Antonio Felici, Pietro Cozzini, Glen E. Kellogg, Carla Borri Voltattorni, Andrea Mozzarelli
Review
Chemistry, Medicinal
Fabrizio Micheli, Christian Heidbreder
EXPERT OPINION ON THERAPEUTIC PATENTS
(2013)
Article
Chemistry, Medicinal
Gabriele Costantino, Marco Mor, Chiara Pecchini, Gian Paolo Vallerini, Elisa Della Turca, Fabrizio Micheli, Angela Worby, Romano Di Fabio, Angelo Giacometti, Adelheid Roth, Emilio Merlo-Pich, Matteo Biagetti, Giorgio Bonanomi, Dino Montanari, Luca Tarsi, Federica Tonelli, Raffaele Longhi, Anna Maria Capelli
LETTERS IN DRUG DESIGN & DISCOVERY
(2013)
Article
Neurosciences
Manolo Mugnaini, Laura Iavarone, Palmina Cavallini, Cristiana Griffante, Beatrice Oliosi, Chiara Savoia, John Beaver, Eugenii A. Rabiner, Fabrizio Micheli, Christian Heidbreder, Anne Andorn, Emilio Merlo Pich, Massimo Bani
NEUROPSYCHOPHARMACOLOGY
(2013)
Article
Chemistry, Organic
Alessandro Tinarelli, Paolo Righi, Goffredo Rosini, Daniele Andreotti, Roberto Profeta, Simone Spada
Article
Chemistry, Medicinal
Alessandro Grillo, Giulia Chemi, Simone Brogi, Margherita Brindisi, Nicola Relitti, Filomena Fezza, Domenico Fazio, Laura Castelletti, Elisabetta Perdona, Andrea Wong, Stefania Lamponi, Alessandra Pecorelli, Mascia Benedusi, Manuela Fantacci, Massimo Valoti, Giuseppe Valacchi, Fabrizio Micheli, Ettore Novellino, Giuseppe Campiani, Stefania Butini, Mauro Maccarrone, Sandra Gemma
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2019)
Article
Chemistry, Applied
Janine K. Tom, Michal M. Achmatowicz, Matthew G. Beaver, John Colyer, Ari Ericson, Tsang-Lin Hwang, Nancy Jiao, Neil F. Langille, Min Liu, Michael A. Lovette, Rahul P. Sangodkar, Srividya Sharvan Kumar, Simone Spada, Damith Perera, Jillian Sheeran, Kiersten Campbell, Timothy Doherty, David D. Ford, Yuan-Qing Fang, Emiliano Rossi, Gabriella Santoni, Sheng Cui, Shawn D. Walker
Summary: This article discusses process development efforts to improve the final methylation step in the AMG 397 drug substance process, culminating in the execution of a Good Manufacturing Practice (GMP) continuous manufacturing process. Through batch kinetic studies and detailed NMR analysis, the critical factors for consistent reaction conversion and obtaining high purity API were identified. Lessons learned from the manufacturing campaign resulted in the development of a second-generation continuous process, which successfully demonstrated improved reaction processing on a 100 g scale.
ORGANIC PROCESS RESEARCH & DEVELOPMENT
(2021)
Article
Chemistry, Medicinal
Fabrizio Micheli
Review
Pharmacology & Pharmacy
Anna Maria Capelli, Fabrizio Micheli
PHARMACEUTICAL PATENT ANALYST
(2012)