NS-018, a selective JAK2 inhibitor, preferentially inhibits CFU-GM colony formation by bone marrow mononuclear cells from high-risk myelodysplastic syndrome patients

Kuroda, Junya; Kodama, Ayumi; Chinen, Yoshiaki; Shimura, Yuji; Mizutani, Shinsuke; Nagoshi, Hisao; Kobayashi, Tsutomu; Matsumoto, Yosuke; Nakaya, Yohei; Tamura, Ayako; Kobayashi, Yutaka; Naito, Hiroshi

doi:10.1016/j.leukres.2014.03.001

Leukemia Research

2014

DOI: 10.1016/j.leukres.2014.03.001

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NS-018, a selective JAK2 inhibitor, preferentially inhibits CFU-GM colony formation by bone marrow mononuclear cells from high-risk myelodysplastic syndrome patients

Junya Kuroda

Ayumi Kodama

Yoshiaki Chinen

et al.

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Cited by 4 publications

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Insight into Janus kinases specificity: From molecular architecture to cancer therapeutics

Wei,

Lu,

Yao

et al. 2024

MedComm – Oncology

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Janus Kinases (JAKs) play a crucial role as therapeutic targets for various cancers. However, the current JAK inhibitors (JAKi) available have limited therapeutic benefits due to their lack of selectivity. This review focuses on the structural analysis to elucidate the molecular determinants of JAKs specificity and the discovery and design of selective JAKi. It includes descriptions and comparison of different JAK structures and their binding sites, a comparative analysis of JAKi and their binding modes, detailed interaction fingerprints (IFPs), and an extensive structure‐selectivity relationship (SSRs). Moreover, the review also explores the challenges and possibilities of using computational structure‐based methods for discovering and designing selective JAKi. Other structure‐based approaches, such as targeting the pseudokinase domain, as well as covalent and allosteric designs, are also covered. Based on this analysis, key determinants corresponding to JAK specificity and rational medicinal chemistry strategies are proposed to facilitate the development of highly selective JAKi. Overall, we aim to enhance the understanding of JAK specificity and explore strategies that can lead to the discovery of effective and selective JAKi in cancer therapy, thus improving the prognosis for cancer patients.

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Insight into Janus kinases specificity: From molecular architecture to cancer therapeutics

Wei,

Lu,

Yao

et al. 2024

MedComm – Oncology

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Mutation-Driven Therapy in MDS

Swoboda

Sallman

2019

Curr Hematol Malig Rep

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Janus kinases (JAKs): The efficient therapeutic targets for autoimmune diseases and myeloproliferative disorders

Shen

et al. 2020

European Journal of Medicinal Chemistry

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NS-018, a selective JAK2 inhibitor, preferentially inhibits CFU-GM colony formation by bone marrow mononuclear cells from high-risk myelodysplastic syndrome patients

Cited by 4 publications

References 34 publications

Insight into Janus kinases specificity: From molecular architecture to cancer therapeutics

Insight into Janus kinases specificity: From molecular architecture to cancer therapeutics

Mutation-Driven Therapy in MDS

Janus kinases (JAKs): The efficient therapeutic targets for autoimmune diseases and myeloproliferative disorders

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