Browsing by Author "Miao, Jinmin"

Now showing 1 - 6 of 6
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    Copper-promoted site-selective carbonylation of sp3 and sp2 C–H bonds with nitromethane
    (RSC, 2016-08) Wu, Xuesong; Miao, Jinmin; Li, Yanrong; Li, Guigen; Ge, Haibo; Department of Chemistry & Chemical Biology, School of Science
    Copper-promoted direct carbonylation of unactivated sp3 C–H and aromatic sp2 C–H bonds of amides was developed using nitromethane as a novel carbonyl source. The sp3 C–H functionalization showed high site-selectivity by favoring the C–H bonds of α-methyl groups. The sp2 C–H carbonylation featured high regioselectivity and good functional group compatibility. Kinetic isotope effect studies indicated that the sp3 C–H bond breaking step is reversible, whereas the sp2 C–H bond cleavage is an irreversible but not the rate-determining step. Control experiments showed that a nitromethyl intermediate should be involved in the present reaction.
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    Palladium-Catalyzed Decarboxylative Alkoxycarbonylation of Potassium Aryltrifluoroborates with Potassium Oxalate Monoesters
    (RSC, 2016-02) Miao, Jinmin; Fang, Ping; Jagdeep, Sahota; Ge, Haibo; Department of Chemistry and Chemical Biology, School of Science
    Palladium-catalyzed decarboxylative alkoxycarbonylation of potassium aryltrifluoroborates with potassium oxalate monoesters in the presence of potassium persulfate was performed under mild conditions. A number of benzoyl esters with a wide variety of substituents at different positions were efficiently synthesized with this method. Mechanism of the palladium-catalyzed decarboxylative carbonylation of aryltrifluoroborates was studied, and a radical-mediated Pd(II)/Pd(IV) catalytic cycle was proposed.
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    Palladium-Catalyzed Site-Selective Fluorination of Unactivated C(sp3)−H Bonds
    (ACS, 2015-07) Miao, Jinmin; Yang, Ke; Kurek, Martin; Ge, Haibo; Department of Chemistry & Chemical Biology, School of Science
    The transition-metal-catalyzed direct C–H bond fluorination is an attractive synthetic tool toward the preparation of organofluorines. While many methods exist for the direct sp3 C–H functionalization, site-selective fluorination of unactivated sp3 carbons remains a challenge. Direct, highly site-selective and diastereoselective fluorination of aliphatic amides via a palladium-catalyzed bidentate ligand-directed C–H bond functionalization process on unactivated sp3 carbons is reported. With this approach, a wide variety of β-fluorinated amino acid derivatives and aliphatic amides, important motifs in medicinal and agricultural chemistry, were prepared with palladium acetate as the catalyst and Selectfluor as the fluorine source.
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    PRL2 phosphatase enhances oncogenic FLT3 signaling via dephosphorylation of the E3 ubiquitin ligase CBL at tyrosine 371
    (American Society of Hematology, 2023) Chen, Hongxia; Bai, Yunpeng; Kobayashi, Michihiro; Xiao, Shiyu; Cai, Wenjie; Barajas, Sergio; Chen, Sisi; Miao, Jinmin; Nguele Meke, Frederick; Vemula, Sasidhar; Ropa, James P.; Croop, James M.; Boswell, H. Scott; Wan, Jun; Jia, Yuzhi; Liu, Huiping; Li, Loretta S.; Altman, Jessica K.; Eklund, Elizabeth A.; Ji, Peng; Tong, Wei; Band, Hamid; Huang, Danny T.; Platanias, Leonidas C.; Zhang, Zhong-Yin; Liu, Yan; Pediatrics, School of Medicine
    Acute myeloid leukemia (AML) is an aggressive blood cancer with poor prognosis. FMS-like tyrosine kinase receptor-3 (FLT3) is one of the major oncogenic receptor tyrosine kinases aberrantly activated in AML. Although protein tyrosine phosphatase PRL2 is highly expressed in some subtypes of AML compared with normal human hematopoietic stem and progenitor cells, the mechanisms by which PRL2 promotes leukemogenesis are largely unknown. We discovered that genetic and pharmacological inhibition of PRL2 significantly reduce the burden of FLT3-internal tandem duplications-driven leukemia and extend the survival of leukemic mice. Furthermore, we found that PRL2 enhances oncogenic FLT3 signaling in leukemia cells, promoting their proliferation and survival. Mechanistically, PRL2 dephosphorylates the E3 ubiquitin ligase CBL at tyrosine 371 and attenuates CBL-mediated ubiquitination and degradation of FLT3, leading to enhanced FLT3 signaling in leukemia cells. Thus, our study reveals that PRL2 enhances oncogenic FLT3 signaling in leukemia cells through dephosphorylation of CBL and will likely establish PRL2 as a novel druggable target for AML.
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    PRL2 Phosphatase Promotes Oncogenic KIT Signaling in Leukemia Cells through Modulating CBL Phosphorylation
    (American Association for Cancer Research, 2024) Chen, Hongxia; Bai, Yunpeng; Kobayashi, Michihiro; Xiao, Shiyu; Barajas, Sergio; Cai, Wenjie; Chen, Sisi; Miao, Jinmin; Meke, Frederick Nguele; Yao, Chonghua; Yang, Yuxia; Strube, Katherine; Satchivi, Odelia; Sun, Jianmin; Rönnstrand, Lars; Croop, James M.; Boswell, H. Scott; Jia, Yuzhi; Liu, Huiping; Li, Loretta S.; Altman, Jessica K.; Eklund, Elizabeth A.; Sukhanova, Madina; Ji, Peng; Tong, Wei; Band, Hamid; Huang, Danny T.; Platanias, Leonidas C.; Zhang, Zhong-Yin; Liu, Yan; Pediatrics, School of Medicine
    Receptor tyrosine kinase KIT is frequently activated in acute myeloid leukemia (AML). While high PRL2 (PTP4A2) expression is correlated with activation of SCF/KIT signaling in AML, the underlying mechanisms are not fully understood. We discovered that inhibition of PRL2 significantly reduces the burden of oncogenic KIT-driven leukemia and extends leukemic mice survival. PRL2 enhances oncogenic KIT signaling in leukemia cells, promoting their proliferation and survival. We found that PRL2 dephosphorylates CBL at tyrosine 371 and inhibits its activity toward KIT, leading to decreased KIT ubiquitination and enhanced AKT and ERK signaling in leukemia cells. Implications: Our studies uncover a novel mechanism that fine-tunes oncogenic KIT signaling in leukemia cells and will likely identify PRL2 as a novel therapeutic target in AML with KIT mutations.
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    SHP2 phosphatase as a novel therapeutic target for melanoma treatment
    (Impact Journals, 2016-11-08) Zhang, Ruo-Yu; Yu, Zhi-Hong; Zeng, Lifan; Zhang, Sheng; Bai, Yunpeng; Miao, Jinmin; Chen, Lan; Xie, Jingwu; Zhang, Zhong-Yin; Department of Biochemistry & Molecular Biology, IU School of Medicine
    Melanoma ranks among the most aggressive and deadly human cancers. Although a number of targeted therapies are available, they are effective only in a subset of patients and the emergence of drug resistance often reduces durable responses. Thus there is an urgent need to identify new therapeutic targets and develop more potent pharmacological agents for melanoma treatment. Herein we report that SHP2 levels are frequently elevated in melanoma, and high SHP2 expression is significantly associated with more metastatic phenotype and poorer prognosis. We show that SHP2 promotes melanoma cell viability, motility, and anchorage-independent growth, through activation of both ERK1/2 and AKT signaling pathways. We demonstrate that SHP2 inhibitor 11a-1 effectively blocks SHP2-mediated ERK1/2 and AKT activation and attenuates melanoma cell viability, migration and colony formation. Most importantly, SHP2 inhibitor 11a-1 suppresses xenografted melanoma tumor growth, as a result of reduced tumor cell proliferation and enhanced tumor cell apoptosis. Taken together, our data reveal SHP2 as a novel target for melanoma and suggest SHP2 inhibitors as potential novel therapeutic agents for melanoma treatment.