A small molecule inhibitor targeting SHP2 mutations for the lung carcinoma

Nian, Qing; Zeng, Jinhao; Li, He; Chen, Yu; Zhang, Zhiqiang; Rodrigues‐Lima, Fernando; Zhao, Liyun; Feng, Xuanlin; Shi, Jianyou

doi:10.1016/j.cclet.2021.01.002

Cited by 7 publications

(2 citation statements)

References 88 publications

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“…An elevated diaphragm decreases caudal longitudinal traction of trachea through mediastinal structure, leading to a worsening of the upper airway patency and increased its resistance. [56][57][58] As mentioned, it could be speculated that R25, which represents upper airway resistance, can more accurately reflect the severity of OSA than R20, representing central airway resistance. The main advantage of IOS is its ability to perform these measurements in a noninvasive, relatively effort independent, and minimally intrusive manner during spontaneous normal tidal breathing.…”

Section: Rv/tlcmentioning

confidence: 99%

Pulmonary Function Test and Obstructive Sleep Apnea Hypopnea Syndrome in Obese Adults: A Retrospective Study

Ying¹,

Liu²,

Li³

et al. 2023

COPD

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We explore risk factors related to severe obstructive sleep apnea (OSA) in obese patients, including pulmonary ventilation function, diffusion function, and impulse oscillometry (IOS) data. Methods:The medical records of 207 obese patients who were prepared to undergo bariatric surgery in a hospital from May 2020 to September 2021 were retrospectively reviewed. Polysomnography (PSG), pulmonary ventilation function, diffusion function, and IOS parameters were collected according to the ethical standards of the institutional research committee (registration number: KYLL-202008-144). Logistic regression analysis was used to analyze the related independent risk factors. Results: There were significantly statistical difference in a number of pulmonary ventilation and diffusion function parameters among the non-OSAHS group, the mild-to-moderate OSA group, and the severe OSA group. However, only airway resistance parameters R5%, R10%, R15%, R20%, R25%, and R35% increased with increasing OSA severity and were positively correlated with apnea hypopnea index (AHI). Age (P = 0.012, 1.104 (1.022, 1.192)), body mass index (P< 0.0001, 1.12 (1.057, 1.187)), gender (P = 0.003, 4.129 (1.625, 10.49)), and R25% (P = 0.007, 1.018 (1.005, 1.031)) were independent risk factors for severe OSA. In patients aged 35 to 60, RV/TLC (P = 0.029, 1.272 (1.025, 1.577)) is an independent risk factor for severe OSA. Conclusion: R25% was an independent risk factor for severe OSA in obese individuals, while RV/TLC was also an independent risk factor in those aged 35 to 60. Pulmonary function tests (PFTs), particularly IOS levels, are recommended to assess severe OSA in obese patients.

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Section: Rv/tlcmentioning

confidence: 99%

Pulmonary Function Test and Obstructive Sleep Apnea Hypopnea Syndrome in Obese Adults: A Retrospective Study

Ying¹,

Liu²,

Li³

et al. 2023

COPD

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“…In past decades, prodrugs have advanced from an old drug discovery strategy to the intentionally designed technique, since it can economically address the pharmacodynamic and pharmacokinetic drawbacks during drug development. [8][9][10][11][12][13][14][15] With the expansion of prodrug strategy, [16][17][18] racemic promoieties were introduced into drug molecules in a manner of physiologically labile stereogenic center [19,20] such as talampicillin, [21] fosinopril, [22] isavuconazonium [23,24] and gabapentin enacarbil. [25,26] These promoiteis can efficiently improve the biopharmaceutical profiles of parent drugs mostly by facilitating absorption in the physiological circumstances.…”

Section: Introductionmentioning

confidence: 99%

Anticancer Effect of Chlorambucil Enhanced by Chiral Phthalidyl Promoiety

Zhang

Cheng

Liu

et al. 2022

Chemistry & Biodiversity

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Phthalidyl promoiety has been used in several drugs, but they were all marketed in racemic form. The pharmaceutical effects of each enantiomer have not been clearly demonstrated. In this project, an anticancer chemotherapy drug, chlorambucil, was modified as enantiopure phthalidyl prodrugs. The enantiomers, together with phthalidyl unit and their racemic mixture, were then subject to the in vivo bioactivity tests against B16F10 melanoma cells. It was found that proper chirality within the promoiety had noticeably better in vivo pharmacological effects than the parent drug, the enantiomer and racemic mixture. This merit perhaps could be extended from the phthalidyl prodrugs to other chirality containing prodrugs.

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Previously Published Phosphatase Probes have Limited Utility Due to their Unspecific Reactivity

ter Brake,

van Luttikhuizen,

van der Wel

et al. 2024

ChemBioChem

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This study explores the use of activity‐based protein profiling to study protein tyrosine phosphatases. With the discovery of allosteric SHP2 inhibitors, this enzyme family has resurfaced as interesting drug targets. Therefore, we envisioned that previously described direct electrophiles and quinone methide‐based traps targeting phosphatases could be applied in competitive activity‐based protein profiling assays. This study evaluates three direct electrophiles, specifically, a vinyl sulfonate, a vinyl sulfone, and an α‐bromobenzylphosphonate as well as three quinone methide‐based traps as activity‐based probes. For all these moieties it was previously shown that they could selectively engage in assays with purified or overexpressed phosphatases in bacterial lysates. However, this study demonstrates that probes based on these moieties all suffer from unspecific labelling. Direct electrophiles were either unspecific or not activity‐based, while quinone methide‐based traps showed dependence on phosphatase activity but also resulted in unspecific labelling due to diffusion after activation. This phenomenon, termed ′bystander’ labelling, occurred even with catalytically inactive SHP2 mutants. We concluded that alternative strategies or chemistries are needed to apply activity‐based protein profiling in phosphatase research. Moreover, this study shows that quinone methide‐based designs have limited potential in probe and inhibitor development strategies due to their intrinsic reactivity.

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A small molecule inhibitor targeting SHP2 mutations for the lung carcinoma

Cited by 7 publications

References 88 publications

Pulmonary Function Test and Obstructive Sleep Apnea Hypopnea Syndrome in Obese Adults: A Retrospective Study

Pulmonary Function Test and Obstructive Sleep Apnea Hypopnea Syndrome in Obese Adults: A Retrospective Study

Anticancer Effect of Chlorambucil Enhanced by Chiral Phthalidyl Promoiety

Previously Published Phosphatase Probes have Limited Utility Due to their Unspecific Reactivity

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