Brigatinib, a newly discovered AXL inhibitor, suppresses AXL-mediated acquired resistance to osimertinib in EGFR-mutated non-small cell lung cancer
In this study we assessed the efficacy of brigatinib, a second-generation of anaplastic lymphoma kinase (ALK)-TKI, as a novel AXL inhibitor, in overcoming acquired resistance to osimertinib induced by AXL activation. We established an AXL-overexpression NSCLC cell line and conducted high-throughput screening of a small molecule chemical library containing 510 anti-tumor drugs. We found that brigatinib potently inhibited AXL expression, and that brigatinib (0.5 μM) significantly enhanced the anti-tumor efficacy of osimertinib (1 μM) in AXL-mediated osimertinib-resistant NSCLC cell lines in vitro. We demonstrated that brig...
Source: Acta Pharmacologica Sinica - March 4, 2024 Category: Drugs & Pharmacology Authors: Rui Han Cong-Hua Lu Chen Hu Yuan-Yao Dou Jun Kang Cai-Yu Lin Di Wu Wei-Ling Jiang Guo-Qing Yin Yong He Source Type: research
Intestinal epithelial Kr üppel-like factor 4 alleviates endotoxemia and atherosclerosis through improving NF-κB/miR-34a-mediated intestinal permeability
In this study we investigated the role of KLF4 in regulating intestinal inflammation and permeability during the atherosclerotic process. Atherosclerotic model was established in ApoE-/- mice by feeding a high fat high cholesterol (HFHC) diet. We showed that colon expression levels of KLF4 and tight junction proteins were significantly decreased whereas inflammatory responses increased in atherosclerotic mice. Overexpression of colon epithelial Klf4 decreased atherosclerotic plaque formation and vascular inflammation in atherosclerotic mice, accompanied by remarkable suppression of intestinal NF-κB activation. We found th...
Source: Acta Pharmacologica Sinica - March 4, 2024 Category: Drugs & Pharmacology Authors: He-Zhong-Rong Nie Yi-Wen Zhou Xiao-Hong Yu Cong-Guo Yin Ling-Fei Li Hui-Qin Hao Tao Yuan Yong Pan Source Type: research
Discovery of a selective TRF2 inhibitor FKB04 induced telomere shortening and senescence in liver cancer cells
Acta Pharmacol Sin. 2024 Mar 4. doi: 10.1038/s41401-024-01243-6. Online ahead of print.ABSTRACTTelomere repeat binding factor 2 (TRF2), a critical element of the shelterin complex, plays a vital role in the maintenance of genome integrity. TRF2 overexpression is found in a wide range of malignant cancers, whereas its down-regulation could cause cell death. Despite its potential role, the selectively small-molecule inhibitors of TRF2 and its therapeutic effects on liver cancer remain largely unknown. Our clinical data combined with bioinformatic analysis demonstrated that TRF2 is overexpressed in liver cancer and that high ...
Source: Acta Pharmacologica Sinica - March 4, 2024 Category: Drugs & Pharmacology Authors: Yin-da Qiu Qi Yan Yi Wang Yan-Fei Ye Yan Wang Meng-Ying Wang Pei-Pei Wang Shu-Yuan Zhang Da-Long Wang Hao Yan Jing Ruan Yun-Jie Zhao Le-Hao Huang Namki Cho Kun Wang Xiao-Hui Zheng Zhi-Guo Liu Source Type: research
α4 nicotinic receptors on GABAergic neurons mediate a cholinergic analgesic circuit in the substantia nigra pars reticulata
Acta Pharmacol Sin. 2024 Mar 4. doi: 10.1038/s41401-024-01234-7. Online ahead of print.ABSTRACTNicotinic acetylcholine receptors (nAChRs) regulate pain pathways with various outcomes depending on receptor subtypes, neuron types, and locations. But it remains unknown whether α4β2 nAChRs abundantly expressed in the substantia nigra pars reticulata (SNr) have potential to mitigate hyperalgesia in pain states. We observed that injection of nAChR antagonists into the SNr reduced pain thresholds in naïve mice, whereas injection of nAChR agonists into the SNr relieved hyperalgesia in mice, subjected to capsaicin injection into...
Source: Acta Pharmacologica Sinica - March 4, 2024 Category: Drugs & Pharmacology Authors: Yu Han Jia-Qi Zhang Ya-Wei Ji Yi-Wen Luan Shu-Yi Li Hui-Zhen Geng Ying Ji Cui Yin Su Liu Chun-Yi Zhou Cheng Xiao Source Type: research
Brigatinib, a newly discovered AXL inhibitor, suppresses AXL-mediated acquired resistance to osimertinib in EGFR-mutated non-small cell lung cancer
In this study we assessed the efficacy of brigatinib, a second-generation of anaplastic lymphoma kinase (ALK)-TKI, as a novel AXL inhibitor, in overcoming acquired resistance to osimertinib induced by AXL activation. We established an AXL-overexpression NSCLC cell line and conducted high-throughput screening of a small molecule chemical library containing 510 anti-tumor drugs. We found that brigatinib potently inhibited AXL expression, and that brigatinib (0.5 μM) significantly enhanced the anti-tumor efficacy of osimertinib (1 μM) in AXL-mediated osimertinib-resistant NSCLC cell lines in vitro. We demonstrated that brig...
Source: Acta Pharmacologica Sinica - March 4, 2024 Category: Drugs & Pharmacology Authors: Rui Han Cong-Hua Lu Chen Hu Yuan-Yao Dou Jun Kang Cai-Yu Lin Di Wu Wei-Ling Jiang Guo-Qing Yin Yong He Source Type: research
Intestinal epithelial Kr üppel-like factor 4 alleviates endotoxemia and atherosclerosis through improving NF-κB/miR-34a-mediated intestinal permeability
In this study we investigated the role of KLF4 in regulating intestinal inflammation and permeability during the atherosclerotic process. Atherosclerotic model was established in ApoE-/- mice by feeding a high fat high cholesterol (HFHC) diet. We showed that colon expression levels of KLF4 and tight junction proteins were significantly decreased whereas inflammatory responses increased in atherosclerotic mice. Overexpression of colon epithelial Klf4 decreased atherosclerotic plaque formation and vascular inflammation in atherosclerotic mice, accompanied by remarkable suppression of intestinal NF-κB activation. We found th...
Source: Acta Pharmacologica Sinica - March 4, 2024 Category: Drugs & Pharmacology Authors: He-Zhong-Rong Nie Yi-Wen Zhou Xiao-Hong Yu Cong-Guo Yin Ling-Fei Li Hui-Qin Hao Tao Yuan Yong Pan Source Type: research
Discovery of a selective TRF2 inhibitor FKB04 induced telomere shortening and senescence in liver cancer cells
Acta Pharmacol Sin. 2024 Mar 4. doi: 10.1038/s41401-024-01243-6. Online ahead of print.ABSTRACTTelomere repeat binding factor 2 (TRF2), a critical element of the shelterin complex, plays a vital role in the maintenance of genome integrity. TRF2 overexpression is found in a wide range of malignant cancers, whereas its down-regulation could cause cell death. Despite its potential role, the selectively small-molecule inhibitors of TRF2 and its therapeutic effects on liver cancer remain largely unknown. Our clinical data combined with bioinformatic analysis demonstrated that TRF2 is overexpressed in liver cancer and that high ...
Source: Acta Pharmacologica Sinica - March 4, 2024 Category: Drugs & Pharmacology Authors: Yin-da Qiu Qi Yan Yi Wang Yan-Fei Ye Yan Wang Meng-Ying Wang Pei-Pei Wang Shu-Yuan Zhang Da-Long Wang Hao Yan Jing Ruan Yun-Jie Zhao Le-Hao Huang Namki Cho Kun Wang Xiao-Hui Zheng Zhi-Guo Liu Source Type: research
α4 nicotinic receptors on GABAergic neurons mediate a cholinergic analgesic circuit in the substantia nigra pars reticulata
Acta Pharmacol Sin. 2024 Mar 4. doi: 10.1038/s41401-024-01234-7. Online ahead of print.ABSTRACTNicotinic acetylcholine receptors (nAChRs) regulate pain pathways with various outcomes depending on receptor subtypes, neuron types, and locations. But it remains unknown whether α4β2 nAChRs abundantly expressed in the substantia nigra pars reticulata (SNr) have potential to mitigate hyperalgesia in pain states. We observed that injection of nAChR antagonists into the SNr reduced pain thresholds in naïve mice, whereas injection of nAChR agonists into the SNr relieved hyperalgesia in mice, subjected to capsaicin injection into...
Source: Acta Pharmacologica Sinica - March 4, 2024 Category: Drugs & Pharmacology Authors: Yu Han Jia-Qi Zhang Ya-Wei Ji Yi-Wen Luan Shu-Yi Li Hui-Zhen Geng Ying Ji Cui Yin Su Liu Chun-Yi Zhou Cheng Xiao Source Type: research
Brigatinib, a newly discovered AXL inhibitor, suppresses AXL-mediated acquired resistance to osimertinib in EGFR-mutated non-small cell lung cancer
In this study we assessed the efficacy of brigatinib, a second-generation of anaplastic lymphoma kinase (ALK)-TKI, as a novel AXL inhibitor, in overcoming acquired resistance to osimertinib induced by AXL activation. We established an AXL-overexpression NSCLC cell line and conducted high-throughput screening of a small molecule chemical library containing 510 anti-tumor drugs. We found that brigatinib potently inhibited AXL expression, and that brigatinib (0.5 μM) significantly enhanced the anti-tumor efficacy of osimertinib (1 μM) in AXL-mediated osimertinib-resistant NSCLC cell lines in vitro. We demonstrated that brig...
Source: Acta Pharmacologica Sinica - March 4, 2024 Category: Drugs & Pharmacology Authors: Rui Han Cong-Hua Lu Chen Hu Yuan-Yao Dou Jun Kang Cai-Yu Lin Di Wu Wei-Ling Jiang Guo-Qing Yin Yong He Source Type: research
Intestinal epithelial Kr üppel-like factor 4 alleviates endotoxemia and atherosclerosis through improving NF-κB/miR-34a-mediated intestinal permeability
In this study we investigated the role of KLF4 in regulating intestinal inflammation and permeability during the atherosclerotic process. Atherosclerotic model was established in ApoE-/- mice by feeding a high fat high cholesterol (HFHC) diet. We showed that colon expression levels of KLF4 and tight junction proteins were significantly decreased whereas inflammatory responses increased in atherosclerotic mice. Overexpression of colon epithelial Klf4 decreased atherosclerotic plaque formation and vascular inflammation in atherosclerotic mice, accompanied by remarkable suppression of intestinal NF-κB activation. We found th...
Source: Acta Pharmacologica Sinica - March 4, 2024 Category: Drugs & Pharmacology Authors: He-Zhong-Rong Nie Yi-Wen Zhou Xiao-Hong Yu Cong-Guo Yin Ling-Fei Li Hui-Qin Hao Tao Yuan Yong Pan Source Type: research
Discovery of a selective TRF2 inhibitor FKB04 induced telomere shortening and senescence in liver cancer cells
Acta Pharmacol Sin. 2024 Mar 4. doi: 10.1038/s41401-024-01243-6. Online ahead of print.ABSTRACTTelomere repeat binding factor 2 (TRF2), a critical element of the shelterin complex, plays a vital role in the maintenance of genome integrity. TRF2 overexpression is found in a wide range of malignant cancers, whereas its down-regulation could cause cell death. Despite its potential role, the selectively small-molecule inhibitors of TRF2 and its therapeutic effects on liver cancer remain largely unknown. Our clinical data combined with bioinformatic analysis demonstrated that TRF2 is overexpressed in liver cancer and that high ...
Source: Acta Pharmacologica Sinica - March 4, 2024 Category: Drugs & Pharmacology Authors: Yin-da Qiu Qi Yan Yi Wang Yan-Fei Ye Yan Wang Meng-Ying Wang Pei-Pei Wang Shu-Yuan Zhang Da-Long Wang Hao Yan Jing Ruan Yun-Jie Zhao Le-Hao Huang Namki Cho Kun Wang Xiao-Hui Zheng Zhi-Guo Liu Source Type: research
α4 nicotinic receptors on GABAergic neurons mediate a cholinergic analgesic circuit in the substantia nigra pars reticulata
Acta Pharmacol Sin. 2024 Mar 4. doi: 10.1038/s41401-024-01234-7. Online ahead of print.ABSTRACTNicotinic acetylcholine receptors (nAChRs) regulate pain pathways with various outcomes depending on receptor subtypes, neuron types, and locations. But it remains unknown whether α4β2 nAChRs abundantly expressed in the substantia nigra pars reticulata (SNr) have potential to mitigate hyperalgesia in pain states. We observed that injection of nAChR antagonists into the SNr reduced pain thresholds in naïve mice, whereas injection of nAChR agonists into the SNr relieved hyperalgesia in mice, subjected to capsaicin injection into...
Source: Acta Pharmacologica Sinica - March 4, 2024 Category: Drugs & Pharmacology Authors: Yu Han Jia-Qi Zhang Ya-Wei Ji Yi-Wen Luan Shu-Yi Li Hui-Zhen Geng Ying Ji Cui Yin Su Liu Chun-Yi Zhou Cheng Xiao Source Type: research
Brigatinib, a newly discovered AXL inhibitor, suppresses AXL-mediated acquired resistance to osimertinib in EGFR-mutated non-small cell lung cancer
In this study we assessed the efficacy of brigatinib, a second-generation of anaplastic lymphoma kinase (ALK)-TKI, as a novel AXL inhibitor, in overcoming acquired resistance to osimertinib induced by AXL activation. We established an AXL-overexpression NSCLC cell line and conducted high-throughput screening of a small molecule chemical library containing 510 anti-tumor drugs. We found that brigatinib potently inhibited AXL expression, and that brigatinib (0.5 μM) significantly enhanced the anti-tumor efficacy of osimertinib (1 μM) in AXL-mediated osimertinib-resistant NSCLC cell lines in vitro. We demonstrated that brig...
Source: Acta Pharmacologica Sinica - March 4, 2024 Category: Drugs & Pharmacology Authors: Rui Han Cong-Hua Lu Chen Hu Yuan-Yao Dou Jun Kang Cai-Yu Lin Di Wu Wei-Ling Jiang Guo-Qing Yin Yong He Source Type: research
Intestinal epithelial Kr üppel-like factor 4 alleviates endotoxemia and atherosclerosis through improving NF-κB/miR-34a-mediated intestinal permeability
In this study we investigated the role of KLF4 in regulating intestinal inflammation and permeability during the atherosclerotic process. Atherosclerotic model was established in ApoE-/- mice by feeding a high fat high cholesterol (HFHC) diet. We showed that colon expression levels of KLF4 and tight junction proteins were significantly decreased whereas inflammatory responses increased in atherosclerotic mice. Overexpression of colon epithelial Klf4 decreased atherosclerotic plaque formation and vascular inflammation in atherosclerotic mice, accompanied by remarkable suppression of intestinal NF-κB activation. We found th...
Source: Acta Pharmacologica Sinica - March 4, 2024 Category: Drugs & Pharmacology Authors: He-Zhong-Rong Nie Yi-Wen Zhou Xiao-Hong Yu Cong-Guo Yin Ling-Fei Li Hui-Qin Hao Tao Yuan Yong Pan Source Type: research
Discovery of a selective TRF2 inhibitor FKB04 induced telomere shortening and senescence in liver cancer cells
Acta Pharmacol Sin. 2024 Mar 4. doi: 10.1038/s41401-024-01243-6. Online ahead of print.ABSTRACTTelomere repeat binding factor 2 (TRF2), a critical element of the shelterin complex, plays a vital role in the maintenance of genome integrity. TRF2 overexpression is found in a wide range of malignant cancers, whereas its down-regulation could cause cell death. Despite its potential role, the selectively small-molecule inhibitors of TRF2 and its therapeutic effects on liver cancer remain largely unknown. Our clinical data combined with bioinformatic analysis demonstrated that TRF2 is overexpressed in liver cancer and that high ...
Source: Acta Pharmacologica Sinica - March 4, 2024 Category: Drugs & Pharmacology Authors: Yin-da Qiu Qi Yan Yi Wang Yan-Fei Ye Yan Wang Meng-Ying Wang Pei-Pei Wang Shu-Yuan Zhang Da-Long Wang Hao Yan Jing Ruan Yun-Jie Zhao Le-Hao Huang Namki Cho Kun Wang Xiao-Hui Zheng Zhi-Guo Liu Source Type: research
