Quantitative systems pharmacology modeling of HER2-positive metastatic breast cancer for translational efficacy evaluation and combination assessment across therapeutic modalities
Acta Pharmacol Sin. 2024 Feb 15. doi: 10.1038/s41401-024-01232-9. Online ahead of print.ABSTRACTHER2-positive (HER2+) metastatic breast cancer (mBC) is highly aggressive and a major threat to human health. Despite the significant improvement in patients' prognosis given the drug development efforts during the past several decades, many clinical questions still remain to be addressed such as efficacy when combining different therapeutic modalities, best treatment sequences, interindividual variability as well as resistance and potential coping strategies. To better answer these questions, we developed a mechanistic quantita...
Source: Acta Pharmacologica Sinica - February 15, 2024 Category: Drugs & Pharmacology Authors: Ya-Ting Zhou Jia-Hui Chu Shu-Han Zhao Ge-Li Li Zi-Yi Fu Su-Jie Zhang Xue-Hu Gao Wen Ma Kai Shen Yuan Gao Wei Li Yong-Mei Yin Chen Zhao Source Type: research

Inflammation-related molecular signatures involved in the anticancer activities of brigatinib as well as the prognosis of EML4-ALK lung adenocarcinoma patient
In this study, we systematically explored the validity of sequential ALK inhibitors (alectinib, lorlatinib, crizotinib, ceritinib and brigatinib) for a heavy-treated patient with EML4-ALK fusion via developing an in vitro and in vivo drug testing system based on patient-derived models. Based on the patient-derived models and clinical responses of the patient, we found that crizotinib might inhibit proliferation of EML4-ALK positive tumors resistant to alectinib and lorlatinib. In addition, NSCLC patients harboring the G1269A mutation, which was identified in alectinib, lorlatinib and crizotinib-resistant NSCLC, showed resp...
Source: Acta Pharmacologica Sinica - February 15, 2024 Category: Drugs & Pharmacology Authors: Fu-Jing Ge Xiao-Yang Dai Yao Qiu Xiang-Ning Liu Chen-Ming Zeng Xiao-Yuan Xu Yi-Dan Chen Hong Zhu Qiao-Jun He Ren-Hua Gai Sheng-Lin Ma Xue-Qin Chen Bo Yang Source Type: research

Inflammation-related molecular signatures involved in the anticancer activities of brigatinib as well as the prognosis of EML4-ALK lung adenocarcinoma patient
Acta Pharmacologica Sinica, Published online: 15 February 2024; doi:10.1038/s41401-024-01230-xInflammation-related molecular signatures involved in the anticancer activities of brigatinib as well as the prognosis of EML4-ALK lung adenocarcinoma patient (Source: Acta Pharmacologica Sinica)
Source: Acta Pharmacologica Sinica - February 15, 2024 Category: Drugs & Pharmacology Authors: Fu-jing Ge Xiao-yang Dai Yao Qiu Xiang-ning Liu Chen-ming Zeng Xiao-yuan Xu Yi-dan Chen Hong Zhu Qiao-jun He Ren-hua Gai Sheng-lin Ma Xue-qin Chen Bo Yang Source Type: research

Quantitative systems pharmacology modeling of HER2-positive metastatic breast cancer for translational efficacy evaluation and combination assessment across therapeutic modalities
Acta Pharmacologica Sinica, Published online: 15 February 2024; doi:10.1038/s41401-024-01232-9Quantitative systems pharmacology modeling of HER2-positive metastatic breast cancer for translational efficacy evaluation and combination assessment across therapeutic modalities (Source: Acta Pharmacologica Sinica)
Source: Acta Pharmacologica Sinica - February 15, 2024 Category: Drugs & Pharmacology Authors: Ya-ting Zhou Jia-hui Chu Shu-han Zhao Ge-li Li Zi-yi Fu Su-jie Zhang Xue-hu Gao Wen Ma Kai Shen Yuan Gao Wei Li Yong-mei Yin Chen Zhao Source Type: research

Transforming growth factor- β receptors: versatile mechanisms of ligand activation
Acta Pharmacol Sin. 2024 Feb 13. doi: 10.1038/s41401-024-01235-6. Online ahead of print.ABSTRACTTransforming growth factor-β (TGF-β) signaling is initiated by activation of transmembrane TGF-β receptors (TGFBR), which deploys Smad2/3 transcription factors to control cellular responses. Failure or dysregulation in the TGF-β signaling pathways leads to pathological conditions. TGF-β signaling is regulated at different levels along the pathways and begins with the liberation of TGF-β ligand from its latent form. The mechanisms of TGFBR activation display selectivity to cell types, agonists, and TGF-β isoforms, enabling...
Source: Acta Pharmacologica Sinica - February 13, 2024 Category: Drugs & Pharmacology Authors: Zheng-Jie Chia Ying-Nan Cao Peter J Little Danielle Kamato Source Type: research

Transforming growth factor- β receptors: versatile mechanisms of ligand activation
Acta Pharmacol Sin. 2024 Feb 13. doi: 10.1038/s41401-024-01235-6. Online ahead of print.ABSTRACTTransforming growth factor-β (TGF-β) signaling is initiated by activation of transmembrane TGF-β receptors (TGFBR), which deploys Smad2/3 transcription factors to control cellular responses. Failure or dysregulation in the TGF-β signaling pathways leads to pathological conditions. TGF-β signaling is regulated at different levels along the pathways and begins with the liberation of TGF-β ligand from its latent form. The mechanisms of TGFBR activation display selectivity to cell types, agonists, and TGF-β isoforms, enabling...
Source: Acta Pharmacologica Sinica - February 13, 2024 Category: Drugs & Pharmacology Authors: Zheng-Jie Chia Ying-Nan Cao Peter J Little Danielle Kamato Source Type: research

Transforming growth factor-β receptors: versatile mechanisms of ligand activation
Acta Pharmacologica Sinica, Published online: 13 February 2024; doi:10.1038/s41401-024-01235-6Transforming growth factor-β receptors: versatile mechanisms of ligand activation (Source: Acta Pharmacologica Sinica)
Source: Acta Pharmacologica Sinica - February 13, 2024 Category: Drugs & Pharmacology Authors: Zheng-Jie Chia Ying-nan Cao Peter J. Little Danielle Kamato Source Type: research

GPCRs involved in metabolic diseases: pharmacotherapeutic development updates
Acta Pharmacol Sin. 2024 Feb 7. doi: 10.1038/s41401-023-01215-2. Online ahead of print.ABSTRACTG protein-coupled receptors (GPCRs) are expressed in a variety of cell types and tissues, and activation of GPCRs is involved in enormous metabolic pathways, including nutrient synthesis, transportation, storage or insulin sensitivity, etc. This review intends to summarize the regulation of metabolic homeostasis and mechanisms by a series of GPCRs, such as GPR91, GPR55, GPR119, GPR109a, GPR142, GPR40, GPR41, GPR43 and GPR120. With deep understanding of GPCR's structure and signaling pathways, it is attempting to uncover the role ...
Source: Acta Pharmacologica Sinica - February 7, 2024 Category: Drugs & Pharmacology Authors: Cheng Jin Hui Chen Li Xie Yuan Zhou Li-Li Liu Jian Wu Source Type: research

Glutamatergic neurons in ventral pallidum modulate heroin addiction via epithalamic innervation in rats
In this study we investigated the function of VPGlu in the context-dependent heroin taking and seeking behavior in male rats under the ABA renewal paradigm. By use of cell-type-specific fiber photometry, we showed that the calcium activity of VPGlu were inhibited during heroin self-administration and context-induced relapse, but activated after extinction in a new context. The drug seeking behavior was accompanied by the decreased calcium signal of VPGlu. Chemogenetic manipulation of VPGlu bidirectionally regulated heroin taking and seeking behavior. Anterograde tracing showed that the lateral habenula, one of the epithala...
Source: Acta Pharmacologica Sinica - February 7, 2024 Category: Drugs & Pharmacology Authors: Ruo-Song Chen Jing Liu Yu-Jun Wang Kuan Ning Jing-Gen Liu Zhi-Qiang Liu Source Type: research

Discovery of a nitroaromatic nannocystin with potent in vivo anticancer activity against colorectal cancer by targeting AKT1
In this study we synthesized a nitroaromatic nannocystin through improved preparation of a key fragment, and characterized its in vitro activity and in vivo efficacy against CRC. We first described the total synthesis of compounds 2-4 featuring Heck macrocyclization to forge their 21-membered macrocycle. In a panel of 7 cancer cell lines from different tissues, compound 4 inhibited the cell viability with IC values of 1-6 nM. In particular, compound 4 (1, 2, 4 nM) inhibited the proliferation of CRC cell lines (HCT8, HCT116 and LoVo) in both concentration and time dependent manners. Furthermore, compound 4 concentration-dep...
Source: Acta Pharmacologica Sinica - February 7, 2024 Category: Drugs & Pharmacology Authors: Han Zhang Fei Xie Xiao-Ya Yuan Xin-Tong Dai Yun-Feng Tian Ming-Ming Sun Si-Qi Yu Jia-You Cai Bin Sun Wei-Cheng Zhang Chang-Liang Shan Source Type: research

GPCRs involved in metabolic diseases: pharmacotherapeutic development updates
Acta Pharmacologica Sinica, Published online: 07 February 2024; doi:10.1038/s41401-023-01215-2GPCRs involved in metabolic diseases: pharmacotherapeutic development updates (Source: Acta Pharmacologica Sinica)
Source: Acta Pharmacologica Sinica - February 7, 2024 Category: Drugs & Pharmacology Authors: Cheng Jin Hui Chen Li Xie Yuan Zhou Li-li Liu Jian Wu Source Type: research

Discovery of a nitroaromatic nannocystin with potent in vivo anticancer activity against colorectal cancer by targeting AKT1
Acta Pharmacologica Sinica, Published online: 07 February 2024; doi:10.1038/s41401-024-01231-wDiscovery of a nitroaromatic nannocystin with potent in vivo anticancer activity against colorectal cancer by targeting AKT1 (Source: Acta Pharmacologica Sinica)
Source: Acta Pharmacologica Sinica - February 7, 2024 Category: Drugs & Pharmacology Authors: Han Zhang Fei Xie Xiao-ya Yuan Xin-tong Dai Yun-feng Tian Ming-ming Sun Si-qi Yu Jia-you Cai Bin Sun Wei-cheng Zhang Chang-liang Shan Source Type: research

Glutamatergic neurons in ventral pallidum modulate heroin addiction via epithalamic innervation in rats
Acta Pharmacologica Sinica, Published online: 07 February 2024; doi:10.1038/s41401-024-01229-4Glutamatergic neurons in ventral pallidum modulate heroin addiction via epithalamic innervation in rats (Source: Acta Pharmacologica Sinica)
Source: Acta Pharmacologica Sinica - February 7, 2024 Category: Drugs & Pharmacology Authors: Ruo-song Chen Jing Liu Yu-jun Wang Kuan Ning Jing-gen Liu Zhi-qiang Liu Source Type: research

Desloratadine alleviates ALS-like pathology in hSOD1 < sup > G93A < /sup > mice via targeting 5HTR < sub > 2A < /sub > on activated spinal astrocytes
In this study, we evaluated the therapeutic effects of desloratadine (DLT), a selective 5HTR2A antagonist, in human SOD1G93A (hSOD1G93A) ALS model mice, and elucidated the underlying mechanisms. HSOD1G93A mice were administered DLT (20 mg·kg-1·d-1, i.g.) from the age of 8 weeks for 10 weeks or until death. ALS onset time and lifespan were determined using rotarod and righting reflex tests, respectively. We found that astrocyte activation accompanying with serotonin receptor 2 A (5HTR2A) upregulation in the spinal cord was tightly associated with ALS-like pathology, which was effectively attenuated by DLT administration. ...
Source: Acta Pharmacologica Sinica - January 29, 2024 Category: Drugs & Pharmacology Authors: Jian Lu An-Xu He Zhuo-Ying Jin Meng Zhang Zhong-Xin Li Fan Zhou Lin Ma Hong-Ming Jin Jia-Ying Wang Xu Shen Source Type: research

tRF3-IleAAT reduced extracellular matrix synthesis in diabetic kidney disease mice by targeting ZNF281 and inhibiting ferroptosis
In conclusion, tRF3-IleAAT inhibits ferroptosis by targeting ZNF281, resulting in the mitigation of ECM synthesis in DKD models, suggesting that tRF3-IleAAT may be an attractive therapeutic target for DKD.PMID:38286833 | DOI:10.1038/s41401-024-01228-5 (Source: Acta Pharmacologica Sinica)
Source: Acta Pharmacologica Sinica - January 29, 2024 Category: Drugs & Pharmacology Authors: Yun-Yang Qiao Jia-Ling Ji Wei-Ling Hou Gao-Ting Qu Shan-Wen Li Xing-Yue Li Ran Jin Yin-Fang Li Hui-Min Shi Ai-Qing Zhang Source Type: research