PD-1/PD-L1
PD-1 or programmed death-1 was first identified and cloned in 1992 as a gene transcriptionally induced upon programmed cell death in T cells. It was subsequently found to be an expressed on activated T, B and myeloid cells, and its cytoplasmic region contains an immunoreceptor tyrosine-based inhibitory motif. PD-1 was a T cell molecule that limited T cell activation and proliferation and promoted tolerance. PD-1 is expressed at low levels by resting T cells and has been shown to be expressed by what some investigators have referred to as “exhausted” T cells in animal models of chronic infection.
In patients with multiple different types of epithelial, hematologic and other malignancies, high levels of PD-1 are detected in circulating and tumor-infiltrating lymphocytes including T cells that are tumor antigen specific, presumably due to chronic antigenic stimulation. These tumor-associated PD-1 expressing effector cells are dysfunctional, and their biological activity can be partially recovered using PD-1 or PD-L1 blocking antibodies. The ligands for the PD-1 receptor are PD-L1 and PD-L2, which are molecules found on antigen-presenting cells, and in the case of PD-L1, it is often expressed on epithelial and other types of tumor cells, resulting in an inhibitory interaction within the tumor microenvironment. The induction of PD-L1 expression by tumor cells may be an adaptive resistance mechanism for tumor cells in response to a developing antitumor immune response. In addition, oncogenic PTEN loss is associated with increased PD-L1 expression in glioma and triple-negative breast cancer cells.
PD-L1 expression can thus also be up-regulated by intrinsic oncogenic pathways as well as interferon-gamma secreted by infiltrating immune cells. PD-L1 and PD-1 are expressed by different cellular components in the tumor microenvironment, where their interaction can inhibit T cell immunity. The engagement of PD-1 by its principal ligand PD-L1 may result in apoptosis in T cells, anergy, “exhaustion”, and secretion of interleukin-10. PD-L1 expression may protect tumor cells expressing it from CD8+T cell-mediated lysis. In addition to PD-1, an interaction between PD-L1 and CD80 has been demonstrated in mouse models. PD-L1 acts as a receptor to “back” transmit signals into T cells and tumor cells to impact on their survival, whose mechanism is yet to be determined. Finally, PD-1 and PD-L1 can be expressed on T regulatory cells and may control their function, and innate immune effectors like NKT cells may also involve the PD-1/PD-L1 circuit.
References
1.Balar AV,et al. Cancer Immunol Immunother. 2017;66(5):551–564.
In patients with multiple different types of epithelial, hematologic and other malignancies, high levels of PD-1 are detected in circulating and tumor-infiltrating lymphocytes including T cells that are tumor antigen specific, presumably due to chronic antigenic stimulation. These tumor-associated PD-1 expressing effector cells are dysfunctional, and their biological activity can be partially recovered using PD-1 or PD-L1 blocking antibodies. The ligands for the PD-1 receptor are PD-L1 and PD-L2, which are molecules found on antigen-presenting cells, and in the case of PD-L1, it is often expressed on epithelial and other types of tumor cells, resulting in an inhibitory interaction within the tumor microenvironment. The induction of PD-L1 expression by tumor cells may be an adaptive resistance mechanism for tumor cells in response to a developing antitumor immune response. In addition, oncogenic PTEN loss is associated with increased PD-L1 expression in glioma and triple-negative breast cancer cells.
PD-L1 expression can thus also be up-regulated by intrinsic oncogenic pathways as well as interferon-gamma secreted by infiltrating immune cells. PD-L1 and PD-1 are expressed by different cellular components in the tumor microenvironment, where their interaction can inhibit T cell immunity. The engagement of PD-1 by its principal ligand PD-L1 may result in apoptosis in T cells, anergy, “exhaustion”, and secretion of interleukin-10. PD-L1 expression may protect tumor cells expressing it from CD8+T cell-mediated lysis. In addition to PD-1, an interaction between PD-L1 and CD80 has been demonstrated in mouse models. PD-L1 acts as a receptor to “back” transmit signals into T cells and tumor cells to impact on their survival, whose mechanism is yet to be determined. Finally, PD-1 and PD-L1 can be expressed on T regulatory cells and may control their function, and innate immune effectors like NKT cells may also involve the PD-1/PD-L1 circuit.
References
1.Balar AV,et al. Cancer Immunol Immunother. 2017;66(5):551–564.
Immunology/Inflammation
Amino Acids and Derivatives(42)
Antiviral(77)
CD110(2)
Cell wall(0)
Complement System(33)
FLAP(9)
Hydroxylase(14)
Interferon Receptor(6)
IRAK(24)
IκB kinase (IKK)(41)
Lipoxygenase(53)
LTR(13)
MyD88(6)
NOS(85)
PD-1/PD-L1(38)
PGE synthase(14)
RLR(4)
ROS(61)
Scavenger Receptor(2)
SphK(3)
STING(27)
TLR(68)
PD-1/PD-L1
-
PD-1/PD-L1-IN-9
产品货号 : M37646
cas no: 2628506-54-5
PD-1/PD-L1-IN-9 是一种有效和具有口服活性的 PD-1/PD-L1 相互作用抑制剂,IC50 值为 3.8 nM。PD-1/PD-L1-IN-9 可以增强免疫细胞对肿瘤细胞的杀伤活性。PD-1/PD-L1-IN-9 在 CT26 小鼠模型中表现出显着的体内抗肿瘤活性。 -
PDL-1 cpd 10
产品货号 : M37623
cas no: 2767424-13-3
PD-L1-IN-1 是一种有效的 PD-L1 抑制剂,IC50 为 115 nM。PD-L1-IN-1与PD-L1蛋白强结合,并在表达 PD-L1 的癌细胞(PC9 和 HCC827 细胞)和外周血单核细胞的共同培养中激发 PD-L1 蛋白,增强后者的抗肿瘤免疫活性。PD-L1-IN-1 显著增加了干扰素 γ 的释放和癌细胞的凋亡诱导,对健康细胞的细胞毒性较低。 -
ARB-272572 hydrochloride
产品货号 : M37366
cas no: 2377524-19-9
ARB-272572 hydrochloride is a small molecule PD-L1 inhibitor with an IC50 value of 400 pM for PD-1/PD-L1 HTRF.ARB-272572 hydrochloride inhibits PD-1/PD-L1 cell signaling by inducing homologous interactions with PD-L1 proteins. -
IMMH 010 maleate
产品货号 : M37361
cas no: 2541982-47-0
IMMH 010 maleate (YPD-30 maleate) is an orally available programmed cell death ligand 1 inhibitor with potential antitumor activity for the study of neurological disorders and advanced malignant solid tumors. -
PD-L1-IN-3
产品货号 : M37233
cas no: 2953044-29-4
PD-L1-IN-3 (Compound 4a) functions as an inhibitor of the PD-1/PD-L1 axis, with an IC50 value of 4.97 nM for PD-L1 inhibition and an EC50 value of 2.70 μM for Jurkat T cell modulation. It antagonizes the PD-1/PD-L1 interaction by binding to the PD-L1 dimer, obstructing PD-1 signaling. This compound is utilized in research pertaining to lung cancer and melanoma [1].