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PD-L1 dimerisation induced by biphenyl derivatives mediates anti-breast cancer activity via the non-immune PD-L1-AKT-mTOR/Bcl2 pathway
by
Zhu, Meng-Yu
, Wu, Yan-Ling
, Awadasseid, Annoor
, Zhang, Hua
, Zhou, Shi-Jia
, Wu, Cai-Yun
, Yu, Qi-Meng
, Zhou, Yong-Nan
, Zhang, Wen
, Shen, Chen-Feng
in
AKT protein
/ Antibodies
/ Apoptosis
/ Bcl-2 protein
/ Bioavailability
/ Biology
/ Biphenyl
/ Biphenyl derivative
/ Breast cancer
/ Cholecystokinin
/ Chromatography
/ Cytotoxicity
/ Design
/ Dimerization
/ Disease control
/ GSK-3β
/ Immune response
/ Immunology
/ Lymphocytes
/ Lymphocytes T
/ non-immune pathway
/ PD-1 protein
/ PD-L1
/ PD-L1 protein
/ Pharmaceutical sciences
/ Phosphorylation
/ Proteins
/ Research Paper
/ TOR protein
/ Tumors
2023
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PD-L1 dimerisation induced by biphenyl derivatives mediates anti-breast cancer activity via the non-immune PD-L1-AKT-mTOR/Bcl2 pathway
by
Zhu, Meng-Yu
, Wu, Yan-Ling
, Awadasseid, Annoor
, Zhang, Hua
, Zhou, Shi-Jia
, Wu, Cai-Yun
, Yu, Qi-Meng
, Zhou, Yong-Nan
, Zhang, Wen
, Shen, Chen-Feng
in
AKT protein
/ Antibodies
/ Apoptosis
/ Bcl-2 protein
/ Bioavailability
/ Biology
/ Biphenyl
/ Biphenyl derivative
/ Breast cancer
/ Cholecystokinin
/ Chromatography
/ Cytotoxicity
/ Design
/ Dimerization
/ Disease control
/ GSK-3β
/ Immune response
/ Immunology
/ Lymphocytes
/ Lymphocytes T
/ non-immune pathway
/ PD-1 protein
/ PD-L1
/ PD-L1 protein
/ Pharmaceutical sciences
/ Phosphorylation
/ Proteins
/ Research Paper
/ TOR protein
/ Tumors
2023
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PD-L1 dimerisation induced by biphenyl derivatives mediates anti-breast cancer activity via the non-immune PD-L1-AKT-mTOR/Bcl2 pathway
by
Zhu, Meng-Yu
, Wu, Yan-Ling
, Awadasseid, Annoor
, Zhang, Hua
, Zhou, Shi-Jia
, Wu, Cai-Yun
, Yu, Qi-Meng
, Zhou, Yong-Nan
, Zhang, Wen
, Shen, Chen-Feng
in
AKT protein
/ Antibodies
/ Apoptosis
/ Bcl-2 protein
/ Bioavailability
/ Biology
/ Biphenyl
/ Biphenyl derivative
/ Breast cancer
/ Cholecystokinin
/ Chromatography
/ Cytotoxicity
/ Design
/ Dimerization
/ Disease control
/ GSK-3β
/ Immune response
/ Immunology
/ Lymphocytes
/ Lymphocytes T
/ non-immune pathway
/ PD-1 protein
/ PD-L1
/ PD-L1 protein
/ Pharmaceutical sciences
/ Phosphorylation
/ Proteins
/ Research Paper
/ TOR protein
/ Tumors
2023
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PD-L1 dimerisation induced by biphenyl derivatives mediates anti-breast cancer activity via the non-immune PD-L1-AKT-mTOR/Bcl2 pathway
Journal Article
PD-L1 dimerisation induced by biphenyl derivatives mediates anti-breast cancer activity via the non-immune PD-L1-AKT-mTOR/Bcl2 pathway
2023
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Overview
Recent studies on biphenyl-containing compounds, a type of PD-1/PD-L1 blocker which binds to PD-L1 and induces dimerisation, have focussed on its immune function. Herein, 10 novel biphenyl derivatives were designed and synthesised. The results of the CCK-8 showed that compounds have different anti-tumour activities for tumour cells in the absence of T cells. Particularly, 12j-4 can significantly induce the apoptosis of MDA-MB-231 cells (IC
50
= 2.68 ± 0.27 μM). In further studies, 12j-4 has been shown to prevent the phosphorylation of AKT by binding to cytoplasmic PD-L1, which induces apoptosis in MDA-MB-231 cells through non-immune pathways. The inhibition of AKT phosphorylation restores the activity of GSK-3β, ultimately resulting in the degradation of PD-L1. Besides, in vivo study indicated that 12j-4 repressed tumour growth in nude mice. As these biphenyls exert their anti-tumour effects mainly through non-immune pathways, they are worthy of further study as PD-L1 inhibitors.
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