☆ 4.1 Article

Development of substituted 7-phenyl-4-aminobenzothieno[3,2-d] pyrimidines as potent LIMK1 inhibitors

MEDCHEMCOMM (2011)

期刊

MEDCHEMCOMM

卷 2, 期 10, 页码 982-986

出版社

ROYAL SOC CHEMISTRY

DOI: 10.1039/c1md00138h

关键词

-

类别

Biochemistry & Molecular Biology Chemistry, Medicinal

资金

Cancer Therapeutics CRC under Australian Government
NHMRC IRIISS [361646]
Victorian State Government

向作者/读者索取更多资源

Protocol

Reagent

摘要

7-Phenyl-4-aminobenzothieno[3,2-d]pyrimidines were previously reported to exhibit moderate LIMK1 inhibition. Further exploration of SAR around the 7-phenyl moiety has led to the development of a lead series with an increased potency for LIMK1. Evaluation of physicochemical and ADME properties, and off-target kinase screens has seen this novel series emerge as a promising platform for a set of tool compounds for evaluating LIMK as a therapeutic target.

作者

我是这篇论文的作者

点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.1

评分不足

次要评分

新颖性

-

重要性

-

科学严谨性

-

评价这篇论文

推荐

Article Chemistry, Medicinal

4-Substituted Thieno[3,2-d]pyrimidines as Dual-Stage Antiplasmodial Derivatives

Prisca Lagardere, Romain Mustiere, Nadia Amanzougaghene, Sebastien Hutter, Jean-Francois Franetich, Nadine Azas, Patrice Vanelle, Pierre Verhaeghe, Nicolas Primas, Dominique Mazier, Nicolas Masurier, Vincent Lisowski

Summary: Malaria remains a major global health problem, and the development of drug resistance poses a challenge. A series of 4-substituted thieno[3,2-d]pyrimidines were found to exhibit activity against different stages of the malaria parasite, with the chloro analogue of Gamhepathiopine showing promising activity against both the erythrocytic and hepatic stages.

PHARMACEUTICALS (2022)

添加到收藏夹

Article Chemistry, Medicinal

New antiplasmodial 4-amino-thieno[3,2-d]pyrimidines with improved intestinal permeability and microsomal stability

Prisca Lagardere, Romain Mustiere, Nadia Amanzougaghene, Sebastien Hutter, Marion Casanova, Jean-Francois Franetich, Shahin Tajeri, Aurelie Malzert-Freon, Sophie Corvaisier, Nadine Azas, Patrice Vanelle, Pierre Verhaeghe, Nicolas Primas, Dominique Mazier, Nicolas Masurier, Vincent Lisowski

Summary: The need for new compounds effective against multiple stages of Plasmodium falciparum development is urgent due to the increasing number of strains resistant to current treatments. In this study, 25 new 4-amino-substituted analogues based on Gamhepathiopine were synthesized and evaluated on both erythrocytic and hepatic stages of the parasite. A promising compound, N2-(tert-butyl)-N [4]-(3-(dimethylamino)propyl)-6-(p-tolyl)thieno[3,2-d]pyrimidine-2,4-diamine, showed improved physicochemical properties, intestinal permeability, and microsomal stability compared to Gamhepathiopine, while maintaining good anti-plasmodial activity on the erythrocytic and hepatic stages of Plasmodium falciparum and P. berghei.

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY (2023)

添加到收藏夹

Article Chemistry, Medicinal

Antiproliferative effect, cell cycle arrest and apoptosis generation of novel 6-substituted N5-formyltetrahydropyrido[3,2-d]pyrimidine derivatives

Chonghui Gao, Mengmeng Yuan, Wei Jiang, Rongrong Wang, Baoyan Zheng, Junyi Liu, Zhili Zhang, Chao Tian, Meng Wang

Summary: A series of 6-substituted tetrahydropyrido[3,2-d]pyrimidines (6a-6k) with a formyl group at N-5 position were designed and synthesized based on previous work. These compounds showed micromolar inhibitory effects against all tested tumor cells and exhibited better antiproliferative activities in HL-60 and HeLa cells. The compound 6-(3,4,5-trimethoxyphenethyl)-5-formyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidine-2,4-diamine (6k) also demonstrated over 50% inhibition rate of dihydrofolate reductase at 20 µM. Further studies revealed that this compound induced cell cycle arrest at the S phase and caused apoptosis.

MEDICINAL CHEMISTRY RESEARCH (2023)

添加到收藏夹

Article Chemistry, Medicinal

Discovery of (2-(4-Substituted phenyl)quinolin-4-yl)(4-isopropylpiperazin-1-yl)methanone Derivatives as Potent Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors

Xiaojing Wang, Lihui Zhang, Xue Wang, Dongqi Zhu, Guangzhao Xu, Honggang Li, Lei Zhang

Summary: Inhibition of PCSK9 plays a significant role in the treatment of hyperlipidemia. A series of novel small-molecule PCSK9/LDLR protein-protein interaction inhibitors were discovered, which showed in vitro lipid lowering ability. These compounds serve as lead structures for the development of oral hypolipidemic drugs.

CHEMMEDCHEM (2023)

添加到收藏夹

Article Biochemistry & Molecular Biology

6-(Tetrazol-5-yl)-7-aminoazolo[1,5-a]pyrimidines as Novel Potent CK2 Inhibitors

Grigoriy V. V. Urakov, Konstantin V. V. Savateev, Svetlana K. K. Kotovskaya, Vladimir L. L. Rusinov, Alexandr A. A. Spasov, Denis A. A. Babkov, Elena V. V. Sokolova

Summary: The study focuses on the synthesis and structure-activity relationship of 6-(tetrazol-5-yl)-7-aminoazolo[1,5-a]pyrimidines as inhibitors of Casein kinase 2 (CK2); The desired compounds showed significant CK2 inhibition, with the leader compound displaying an IC50 of 45 nM.

MOLECULES (2022)

添加到收藏夹

Article Chemistry, Organic

Synthesis of 7-Arylpurines from Substituted Pyrimidines

Armands Sebris, Irina Novosjolova, Maris Turks

Summary: A simple three-step approach is described for the synthesis of substituted N7-arylpurines with an overall yield of the whole sequence from 40% to 71%. N7-Arylpurines were constructed by de novo synthesis from commercially available substituted 4-chloropyrimidine-5-amines. Different substituents at purine C2 and C6 positions were obtained by changing the corresponding substituents of the starting pyrimidine. Heteroaromatic, electron-deficient, and electron-rich aromatic groups were then attached to the exocyclic amino group by iodane reagents under copper catalysis. The resulting moiety is further prepared to become purine N7 position after the ring closure. Finally, the substitution at purine C8 position was varied during the last step of the developed sequence by employing different reagents for the purine ring closing reactions or post functionalization.

SYNTHESIS-STUTTGART (2022)

添加到收藏夹

Article Biochemistry & Molecular Biology

Design, synthesis and molecular docking of new fused 1H-pyrroles, pyrrolo[3,2-d]pyrimidines and pyrrolo[3,2-e][1,4]diazepine derivatives as potent EGFR/CDK2 inhibitors

Amany Belal, Nagwa M. Abdel Gawad, Ahmed B. M. Mehany, Mohammed A. S. Abourehab, Hazem Elkady, Ahmed A. Al-Karmalawy, Ahmed S. Ismael

Summary: A new series of compounds with potential EGFR inhibitory activity were designed and synthesized. These compounds showed promising anticancer activity and have the potential for therapeutic use.

JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY (2022)

添加到收藏夹

Article Chemistry, Medicinal

The discovery of novel antitrypanosomal 4-phenyl-6-(pyridin-3-yl) pyrimidines

William J. Robinson, Annie E. Taylor, Solange Lauga-Cami, George W. Weaver, Randolph Rj Arroo, Marcel Kaiser, Sheraz Gul, Maria Kuzikov, Bernhard Ellinger, Kuldip Singh, Tanja Schirmeister, Adolfo Botana, Chatchakorn Eurtivong, Avninder S. Bhambra

Summary: Human African trypanosomiasis, or sleeping sickness, is a neglected tropical disease caused by Trypanosoma brucei rhodesiense and Trypanosoma brucei gambiense, with current therapy limitations and the need for further investigation. Novel anti-trypanosomal compounds show promising potential, providing scaffolds for future drug development targeting the disease.

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY (2021)

添加到收藏夹

Article Biochemistry & Molecular Biology

Synthesis and Neurotropic Activity of New Heterocyclic Systems: Pyridofuro[3,2-d]pyrrolo[1,2-a]pyrimidines, Pyridofuro[3,2-d]pyrido[1,2-a]pyrimidines and Pyridofuro[3 ',2 ':4,5]pyrimido[1,2-a]azepines

Samvel N. Sirakanyan, Domenico Spinelli, Athina Geronikaki, Victor Kartsev, Elmira K. Hakobyan, Anthi Petrou, Ruzanna G. Paronikyan, Ivetta M. Nazaryan, Hasmik H. Akopyan, Anush A. Hovakimyan

Summary: The study identified newly synthesized compounds that exhibit protection against pentylenetetrazole seizures, as well as showing anti-anxiety and antidepressant effects. These compounds have a dual inhibitory effect on the GABA A receptor.

MOLECULES (2021)

添加到收藏夹

Article Chemistry, Medicinal

Discovery of novel pyrido[3,2-d]pyrimidine derivatives as selective and potent PI3Kδ inhibitors

Huanrong Bai, Jiajia Sun, Hao Lei, San-Qi Zhang, Bo Yuan, Mengyan Ma, Minhang Xin

Summary: This study investigated a series of pyrido[3,2-d]pyrimidine derivatives for their bioactivity, and compound S5 showed excellent enzyme activity and antiproliferation activity, making it a potential candidate for further investigation as a PI3K delta inhibitor.

DRUG DEVELOPMENT RESEARCH (2023)

添加到收藏夹

Article Biochemistry & Molecular Biology

Design, synthesis, and biological evaluation of 2-arylamino-4-(piperidi- n-4-yloxy)pyrimidines as potent EGFRT790M/L858R inhibitors to treat non-small cell lung cancer

Liangliang Tian, Xing Li, Zhenying Lv, Yin Yang, Luhong Wang, Dawei Xu, Xiaodong Ma, Youjun Xu

Summary: In this study, three types of novel covalent EGFR T790M/L858R inhibitors were designed and synthesized. The most promising compound, 9i, exhibited potent inhibitory effects against EGFRT790M/L858R and H1975 cells, while showing low cytotoxicity. This research provides important clues for the development of new covalent EGFR inhibitors for the treatment of NSCLC.

BIOORGANIC & MEDICINAL CHEMISTRY (2022)

添加到收藏夹

Article Chemistry, Multidisciplinary

Design, synthesis, and in vitro/vivo anticancer activity of 4-substituted 7-(3-fluoro-4-methoxybenzyl)-7H-pyrrolo[2,3-d]pyrimidines

Pei-Yi Tsai, Gong-Siang Hu, Po-Hsun Huang, Huei-Lin Jheng, Chi-Hsuan Lan, You-Sin Chen, Jia-Ming Chang, Shih-Hsien Chuang, Jiann-Jyh Huang

Summary: This paper reports the design and synthesis of a novel anticancer agent, with compound 6q demonstrating significant antiproliferative activity against various cancer cells and displaying in vivo activity in nude mice. Compound 6q has potential as a lead compound for further optimization in anticancer drug development.

JOURNAL OF THE CHINESE CHEMICAL SOCIETY (2021)

添加到收藏夹

Article Chemistry, Medicinal

Discovery of Thieno[3,2-d]pyrimidine derivatives as potent and selective inhibitors of ataxia telangiectasia mutated and Rad3 related (ATR) kinase

Yunxin Duan, Haodong Cheng, Lili Zhuang, Jiawei Xia, Yerong Xu, Ruyue Zhang, Rui Sun, Tao Lu, Yadong Chen

Summary: ATR kinase is crucial in the DNA damage response and its inhibition could induce synthetic lethality (SL) with DDR deficiencies. We developed a series of selective and potent ATR inhibitors with a thieno[3,2-d]pyrimidine scaffold. Compound 34 was identified as a representative molecule that effectively inhibited ATR kinase and showed antiproliferative effects against cancer cells. Compound 34 also demonstrated good pharmacokinetic properties, in vivo antitumor efficacy, and no obvious toxicity, making it a promising lead compound for drug development.

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY (2023)

添加到收藏夹

Article Biochemistry & Molecular Biology

2-Alkyl-Substituted-4-Amino-Thieno[2,3-d]Pyrimidines: Anti-Proliferative Properties to In Vitro Breast Cancer Models

Ivan Iliev, Anelia Mavrova, Denitsa Yancheva, Stefan Dimov, Galya Staneva, Alexandrina Nesheva, Iana Tsoneva, Biliana Nikolova

Summary: In this study, 2-alkyl derivatives of thienopyrimidine were synthesized and their cytotoxicity and anti-proliferative properties were evaluated. The results showed that these compounds exhibited anti-proliferative activity against cancer cells without cytotoxicity to normal cells.

MOLECULES (2023)

添加到收藏夹

Article Chemistry, Medicinal

Novel 2-phenyl-3-(Pyridin-2-yl) thiazolidin-4-one derivatives as potent inhibitors for proliferation of osteosarcoma cells in vitro and in vivo

Yaqi Deng, Rou Pi, Li Niu, Yun Zhao, Dan Ni, Longlong Song, Zi Li, Wangyujing Han, Qinghua Wei, Yuqiao Han, Tong Zhu, Zhengli Luo, Donghui Sun, Suzhen Dong, Shunying Liu

Summary: This study identified a potential drug candidate for the treatment of osteosarcoma, which demonstrated significant cellular potency and in vivo efficacy by modulating the solubility of compounds. The candidate compound also showed inhibition of OS cell migration.

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY (2022)

添加到收藏夹

Article Biochemistry & Molecular Biology

Optimization of Phosphotyrosine Peptides that Target the SH2 Domain of SOCS1 and Block Substrate Ubiquitination

Hao Chen, Yuntong Wu, Kunlun Li, Iain Currie, Narelle Keating, Farhad Dehkhoda, Christoph Grohmann, Jeffrey J. Babon, Sandra E. Nicholson, Brad E. Sleebs

Summary: Suppressor of cytokine signaling 1 (SOCS1) has been identified as a potential therapeutic target for inflammatory and viral diseases. This study successfully identified specific phosphotyrosine peptides that have high affinity and selectivity for the SH2 domain of SOCS1. These findings provide insights for the development of cell-permeable peptidomimetics targeting the SOCS1-SH2 domain for the treatment of inflammatory and viral diseases.

ACS CHEMICAL BIOLOGY (2022)

添加到收藏夹

Article Microbiology

A revised mechanism for how Plasmodium falciparum recruits and exports proteins into its erythrocytic host cell

Mikha Gabriela, Kathryn M. Matthews, Cas Boshoven, Betty Kouskousis, Thorey K. Jonsdottir, Hayley E. Bullen, Joyanta Modak, David L. Steer, Brad E. Sleebs, Brendan S. Crabb, Tania F. de Koning-Ward, Paul R. Gilson

Summary: The malaria parasite Plasmodium falciparum exports a large number of proteins into host erythrocytes, modifying the physiology of the host cells. This study has identified a subcomplex consisting of EXP2 and PTEX150 that facilitates the docking of HSP101. It has also demonstrated that HSP101 can interact with specific cargo proteins in the parasite's ER and guide them to the parasitophorous vacuole membrane. These findings provide insights into the mechanism of how exported proteins are targeted to PTEX.

PLOS PATHOGENS (2022)

添加到收藏夹

Article Chemistry, Multidisciplinary

Development of 1,2,4-Oxadiazole Antimicrobial Agents to Treat Enteric Pathogens within the Gastrointestinal Tract

Noel P. Pitcher, Jitendra R. Harjani, Yichao Zhao, Jianwen Jin, Daniel R. Knight, Lucy Li, Papanin Putsathit, Thomas Riley, Glen P. Carter, Jonathan B. Baell

Summary: Colonization of pathogenic bacteria in the GI tract is a significant risk factor for healthcare-associated infections. Efforts to develop effective decolonization agents have been largely unsuccessful. This study modified antimicrobial compounds to target bacterial pathogens in the GI tract and identified potential candidates for further development of colon-targeted antimicrobial agents.

ACS OMEGA (2022)

添加到收藏夹

Article Chemistry, Medicinal

A High-Throughput Phenotypic Screen of the 'Pandemic Response Box' Identifies a Quinoline Derivative with Significant Anthelmintic Activity

Harrison T. Shanley, Aya C. Taki, Joseph J. Byrne, Abdul Jabbar, Tim N. C. Wells, Kirandeep Samby, Peter R. Boag, Nghi Nguyen, Brad E. Sleebs, Robin B. Gasser

Summary: Parasitic nematodes cause economic losses in the agricultural industry and the widespread resistance to anthelmintic compounds highlights the need for new treatments. In this study, a screening of 400 compounds led to the discovery of MMV1581032, which exhibited significant inhibition of the motility and development of Haemonchus contortus and Caenorhabditis elegans. MMV1581032 has favorable characteristics and promising potential as a nematocide.

PHARMACEUTICALS (2022)

添加到收藏夹

Article Biochemistry & Molecular Biology

Structure-function analysis of the AMPK activator SC4 and identification of a potent pan AMPK activator

Ashley J. Ovens, Yi Sing Gee, Naomi X. Y. Ling, Dingyi Yu, Justin P. Hardee, Jin D. Chung, Kevin R. W. Ngoei, Nicholas J. Waters, Nolan J. Hoffman, John W. Scott, Kim Loh, Katrin Spengler, Regine Heller, Michael W. Parker, Gordon S. Lynch, Fei Huang, Sandra Galic, Bruce E. Kemp, Jonathan B. Baell, Jonathan S. Oakhill, Christopher G. Langendorf

Summary: AMPK is a cellular energy sensor and regulator of energy homeostasis. Activating AMPK shows potential for treating type 2 diabetes and insulin resistance. Recent studies suggest that the ??202??1 isoform combination is primarily responsible for these effects. Structure/function analysis of SC4 activator led to the discovery of MSG010 and MSG011, which show greater potency in activating ??202??1 AMPK compared to MK-8722. These findings guide the development of selective AMPK activators.

BIOCHEMICAL JOURNAL (2022)

添加到收藏夹

Article Cell Biology

The Medicines for Malaria Venture Malaria Box contains inhibitors of protein secretion in Plasmodium falciparum blood stage parasites

Oliver Looker, Madeline G. Dans, Hayley E. Bullen, Brad E. Sleebs, Brendan S. Crabb, Paul R. Gilson

Summary: This study identified a new compound that inhibits protein export in Plasmodium falciparum parasites, leading to reduced virulence and potential elimination of the parasites.

TRAFFIC (2022)

添加到收藏夹

Article Chemistry, Medicinal

Discovery of Anti-tubercular Analogues of Bedaquiline with Modified A-, B- and C-Ring Subunits

Lisa Barbaro, Gayathri Nagalingam, James A. Triccas, Lendl Tan, Nicholas P. West, Daniel L. Priebbenow, Jonathan B. Baell

Summary: The clinical use of bedaquiline has been limited due to safety concerns. Recent investigations have found that modification of the B- and C-ring units of bedaquiline can lead to the development of new compounds with potent anti-tubercular activity but improved safety. Concurrent modification of the A-, B-, and C-ring units in bedaquiline variants has been shown to result in compounds with relatively potent anti-tubercular activity and reduced safety issues.

CHEMMEDCHEM (2023)

添加到收藏夹

Article Chemistry, Medicinal

Hit-to-lead optimization of novel phenyl imidazole carboxamides that are active against Leishmania donovani

Nicole McNamara, Eleanor Saunders, Swapna Varghese, Rebecca Zheng, Kaylene Simpson, Devika M. Varma, Monica M. Johnson, M. Shamim Hasan Zahid, Eric M. Bachelder, Kristy M. Ainslie, Joo Hwan No, Dahae Koh, David Shum, Nirmal Das, Binita Patra, Jayasree Roy, Arindam Talukdar, Dipyman Ganguly, Malcolm McConville, Jonathan Baell

Summary: In this study, the structure-activity relationship of a novel hit compound was explored. The compound showed improved potency with low cytotoxicity against human cells, indicating its potential as a treatment for visceral leishmaniasis.

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY (2022)

添加到收藏夹

Article Oncology

Targeting cell cycle and apoptosis to overcome chemotherapy resistance in acute myeloid leukemia

Victoria Y. Ling, Jasmin Straube, William Godfrey, Rohit Haldar, Yashaswini Janardhanan, Leanne Cooper, Claudia Bruedigam, Emily Cooper, Paniz Tavakoli Shirazi, Sebastien Jacquelin, Siok-Keen Tey, Jonathan Baell, Fei Huang, Jianwen Jin, Yichao Zhao, Lars Bullinger, Megan J. Bywater, Steven W. Lane

Summary: This study identifies defective cell cycle arrest as a clinically relevant contributor to chemoresistance in acute myeloid leukemia (AML). Downregulation of CDKN2A is associated with inferior overall survival in AML patients and occurs at relapse. Therapeutic targeting of the G(1)S cell cycle restriction point and promotion of apoptosis can enhance chemotherapy response in AML.

LEUKEMIA (2023)

添加到收藏夹

Article Biochemistry & Molecular Biology

Design and characterization of a heterobifunctional degrader of KEAP1

Hao Chen, Nghi H. Nguyen, Charlene M. Magtoto, Simon A. Cobbold, Grace M. Bidgood, Lizeth G. Meza Guzman, Lachlan W. Richardson, Jason Corbin, Amanda E. Au, Bernhard C. Lechtenberg, Rebecca Feltham, Kate D. Sutherland, Christoph Grohmann, Sandra E. Nicholson, Brad E. Sleebs

Summary: A proteolysis targeting chimera (PROTAC) that depletes KEAP1 and activates the NRF2 antioxidant response has been developed as a potential strategy to treat diseases caused by oxidative stress. The optimized PROTAC 14 demonstrated potent KEAP1 degradation and increased expression of antioxidant proteins, effectively preventing cell death induced by reactive oxygen species. This approach presents an alternative therapeutic strategy for oxidative stress-related diseases.

REDOX BIOLOGY (2023)

添加到收藏夹

Review Chemistry, Medicinal

Chemo-proteomics in antimalarial target identification and engagement

Brodie L. L. Bailey, William Nguyen, Alan F. F. Cowman, Brad E. E. Sleebs

Summary: Humans have been battling malaria for thousands of years, and although much progress has been made, certain regions still struggle with the disease, impacting social and economic development. The threat of resistance to current antimalarial treatments raises concerns, making it crucial to develop new chemotypes. Phenotypic screening has been successful in discovering new chemotypes, but the lack of information on their molecular targets hinders clinical development. Chemo-proteomics, a multidisciplinary approach, has been utilized to identify and validate targets, and this review provides insights on its methodology, practicalities, merits, and limitations in antimalarial development.

MEDICINAL RESEARCH REVIEWS (2023)

添加到收藏夹

Article Cell Biology

Sequence elements within the PEXEL motif and its downstream region modulate PTEX-dependent protein export in Plasmodium falciparum

Mikha Gabriela, Claudia B. G. Barnes, Dickson Leong, Brad E. Sleebs, Molly Parkyn Schneider, Dene R. Littler, Brendan S. Crabb, Tania F. de Koning-Ward, Paul R. Gilson

Summary: This article investigates the dual role of the P-2' position E/Q/D residue in the PEXEL motif of exported proteins, playing a role in plasmepsin V cleavage in the endoplasmic reticulum and efficient PTEX-mediated export into the red blood cells. The study also reveals that the spacer region between the PEXEL motif and the folded functional region of the protein controls cargo interaction with PTEX.

TRAFFIC (2023)

添加到收藏夹

Review Chemistry, Multidisciplinary

Australian chemistry and drug discovery towards the development of antimalarials

Brad E. Sleebs

Summary: Malaria, a disease caused by the Plasmodium parasite, results in over 450,000 deaths annually. Resistance to current antimalarial drugs has become a major concern, emphasizing the need for new therapies. Australian scientists have made significant contributions to malaria research, particularly in the development of new antimalarial therapies.

AUSTRALIAN JOURNAL OF CHEMISTRY (2022)

添加到收藏夹

Article Immunology

The acetyltransferase KAT7 is required for thymic epithelial cell expansion, expression of AIRE target genes, and thymic tolerance

Melanie Heinlein, Luke C. Gandolfo, Kelin Zhao, Charis E. Teh, Nghi Nguyen, Jonathan B. Baell, Yael Goldfarb, Jakub Abramson, Johannes Wichmann, Anne K. Voss, Andreas Strasser, Gordon K. Smyth, Tim Thomas, Daniel H. D. Gray

Summary: The histone acetyltransferase KAT7 plays a critical role in promoting transcription of peripheral tissue genes and regulating immunological tolerance in thymic epithelial cells. Deficiency of KAT7 leads to impaired immunological tolerance and the development of autoimmune diseases.

SCIENCE IMMUNOLOGY (2022)

添加到收藏夹

Article Biochemistry & Molecular Biology

Target 2035-update on the quest for a probe for every protein

Susanne Mueller, Suzanne Ackloo, Arij Al Chawaf, Bissan Al-Lazikani, Albert Antolin, Jonathan B. Baell, Hartmut Beck, Shaunna Beedie, Ulrich A. K. Betz, Gustavo Arruda Bezerra, Paul E. Brennan, David Brown, Peter J. Brown, Alex N. Bullock, Adrian J. Carter, Apirat Chaikuad, Mathilde Chaineau, Alessio Ciulli, Ian Collins, Jan Dreher, David Drewry, Kristina Edfeldt, Aled M. Edwards, Ursula Egner, Stephen Frye, Stephen M. Fuchs, Matthew D. Hall, Ingo Hartung, Alexander Hillisch, Stephen H. Hitchcock, Evert Homan, Natarajan Kannan, James R. Kiefer, Stefan Knapp, Milka Kostic, Stefan Kubicek, Andrew R. Leach, Sven Lindemann, Brian D. Marsden, Hisanori Matsui, Jordan L. Meier, Daniel Merk, Maurice Michel, Maxwell R. Morgan, Anke Mueller-Fahrnow, Dafydd R. Owen, Benjamin G. Perry, Saul H. Rosenberg, Kumar Singh Saikatendu, Matthieu Schapira, Cora Scholten, Sujata Sharma, Anton Simeonov, Michael Sundstrom, Giulio Superti-Furga, Matthew H. Todd, Claudia Tredup, Masoud Vedadi, Frank von Delft, Timothy M. Willson, Georg E. Winter, Paul Workman, Cheryl H. Arrowsmith

Summary: Twenty years after the first draft of the human genome was published, our understanding of the human proteome is still incomplete. The majority of proteins in the human proteome remain uncharacterized, with only a small percentage successfully targeted for drug discovery. Target 2035 aims to bridge this gap by developing new technologies for the entire human proteome by 2035.

RSC MEDICINAL CHEMISTRY (2022)

添加到收藏夹

暂无数据

© Peeref 2019-2024. All rights reserved.