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programmed cell death 1 ligand 1   Click here for help

GtoPdb Ligand ID: 9606

Abbreviated name: PD-L1
Synonyms: B7 homolog 1 | B7-H1 | PDL1 | programmed death ligand 1
Immunopharmacology Ligand
Compound class: Endogenous peptide in human, mouse or rat
Comment: This is one of the ligands for the PD-1 receptor. It is a single-pass type I membrane protein. The PD-L1/PD-1 interaction is an established immune checkpoint. Both the ligand and receptor are targets for novel immuno-oncology therapeutics, as over-expression of either of these proteins is a mechanism used by tumour cells to evade immune detection and destruction. Already the target of approved immunotherapeutics in the form of monoclonal antibodies, small molecules targeting the PD-1/PD-L1 checkpoint are now in development to address the shortcomings associated with the current antibody therapies (including, poor susceptibility rate to single immune checkpoint pathway inhibitors, long half-life of antibodies and association with the development of adverse events, problems connected to the requirement for intravenous infusions) [9,20].
Species: Human
Bioactivity Comments
Posttranslational extracellular lactylation of PD-L1 extracellular domain lysines (catalysed by lactyltransferase HAT1) is reported as a key mechanism that contributes to its role in promoting immune evasion in tumours [22].
Natural/Endogenous Targets
Target
programmed cell death 1 (CD279)
Selectivity at other protein targets
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
programmed cell death 1 (CD279) Ligand is endogenous in the given species Hs None Binding - - -
⤷
Other ligands which bind to or alter the activity of this ligand
Key to terms and symbols Click column headers to sort
Ligand Sp. Type Action Value Parameter Concentration range (M) Reference
atezolizumab Peptide Approved drug Primary target of this compound Hs Antibody Binding 9.0 – 10.0 pKd - 10
⤷ pKd 9.0 – 10.0 (Kd 1x10-9 – 1x10-10 M) [10]
cosibelimab Peptide Approved drug Monkey Antibody Binding 9.3 pKd - 1
⤷ pKd 9.3 (Kd 5.6x10-10 M) [1]
cosibelimab Peptide Approved drug Primary target of this compound Hs Antibody Binding 9.1 pKd - 1
⤷ pKd 9.1 (Kd 8.5x10-10 M) [1]
durvalumab Peptide Approved drug Primary target of this compound Hs Antibody Binding 8.7 pKd - 19
⤷ pKd 8.7 (Kd 2x10-9 M) [19]
envafolimab Peptide Approved drug Primary target of this compound Hs Antibody Binding 8.5 pKd - 29
⤷ pKd 8.5 (Kd 3x10-9 M) [29]
X14 Small molecule or natural product Hs Inhibitor Binding 7.8 pKd - 27
⤷ pKd 7.8 (Kd 1.462x10-8 M) [27]
S4-1 Small molecule or natural product Hs Inhibitor Binding 7.2 pKd - 24
⤷ pKd 7.2 (Kd 7.136x10-8 M) [24]
Description: Binding affinity for hPD-L1 using a microscale thermophoresis (MST) assay
PD-L1 inhibitor D6 [PMID: 40153736] Small molecule or natural product Hs Inhibitor Binding 6.6 pKd - 16
⤷ pKd 6.6 (Kd 2.3x10-7 M) [16]
Description: Binding affinity for dimeric hPD-L1
X14 Small molecule or natural product Mm Inhibitor Binding 6.4 pKd - 27
⤷ pKd 6.4 (Kd 3.92x10-7 M) [27]
EP26 Small molecule or natural product Mm Inhibitor Binding 6.3 pKd - 28
⤷ pKd 6.3 (Kd 5.2x10-7 M) [28]
Description: Binding affinity for mouse PD-L1 determined by SPR assay.
EP26 Small molecule or natural product Hs Inhibitor Binding 6.2 pKd - 28
⤷ pKd 6.2 (Kd 5.8x10-7 M) [28]
Description: Binding affinity for human PD-L1 determined by SPR assay.
avelumab Peptide Approved drug Primary target of this compound Hs Antibody Binding 10.1 pIC50 - 18
⤷ pIC50 10.1 (IC50 7.1x10-11 M) [18]
Description: Measuring inhibition of PD-1 binding to PD-L1.
BMS-1166 Small molecule or natural product Hs Inhibitor Binding 8.9 pIC50 - 2,9
⤷ pIC50 8.9 (IC50 1.4x10-9 M) [2,9]
Description: Measured in a PD-1/PD-L1 homogenous time-resolved fluorescence (HTRF) binding assay.
BMS-1001 Small molecule or natural product Primary target of this compound Hs Inhibitor Binding 8.6 pIC50 - 2
⤷ pIC50 8.6 (IC50 2.25x10-9 M) [2]
Description: Measured in a PD-1/PD-L1 homogenous time-resolved fluorescence (HTRF) binding assay.
S4-1 Small molecule or natural product Hs Inhibitor Inhibition 8.2 pIC50 - 24
⤷ pIC50 8.2 (IC50 6.1x10-9 M) [24]
Description: Inhibition of the PD-L1/PD-1 interaction determined in a TR-FRET assay
INCB086550 Small molecule or natural product Hs Inhibitor Inhibition >8.0 pIC50 - 26
⤷ pIC50 >8.0 (IC50 <1x10-8 M) [26]
Description: Measuring inhibition of binding of PD-L1 to its receptor PD-1; binned value from patent
X14 Small molecule or natural product Hs Inhibitor Binding 7.8 pIC50 - 27
⤷ pIC50 7.8 (IC50 1.573x10-8 M) [27]
Description: Potency of inhibiting PD-1/PD-L1 interaction.
BMS-202 Small molecule or natural product Hs Inhibitor Inhibition 7.0 – 7.7 pIC50 - 9,27-28
⤷ pIC50 7.7 (IC50 1.8x10-8 M) [9]
pIC50 7.4 (IC50 3.619x10-8 M) [27]
Description: Potency of inhibiting PD-1/PD-L1 interaction.
pIC50 7.0 (IC50 9.46x10-8 M) [28]
Description: Inhibition of the PD-L1/PD-1 interaction determined by an HTRF FRET-based assay.
PD-L1/VISTA dual inhibitor P17 Small molecule or natural product Hs Inhibitor Inhibition 6.8 pIC50 - 23
⤷ pIC50 6.8 (IC50 1.49x10-7 M) [23]
Description: Inhibition of PD-L1/PD-1 interaction determined by TR-FRET
EP26 Small molecule or natural product Hs Inhibitor Inhibition 5.8 pIC50 - 28
⤷ pIC50 5.8 (IC50 1.77x10-6 M) [28]
Description: Inhibition of PD-L1/PD-1 protein-protein interaction determined in an HTRF FRET-based binding assay.
compound T.14 Small molecule or natural product Hs Inhibitor Binding - - - 3
⤷ [3]
Example 4 [WO2017202275A1] Small molecule or natural product Hs None Binding - - - 5
⤷ [5]
bintrafusp alfa Peptide Primary target of this compound Hs Antibody Binding - - - 12
⤷ [12]
sugemalimab Peptide Approved drug Hs Antibody Binding - - - 6
⤷ [6]
adebrelimab Peptide Approved drug Hs Antibody Binding - - -
⤷
benmelstobart Peptide Approved drug Primary target of this compound Hs Antibody Binding - - -
⤷
tagitanlimab Peptide Approved drug Primary target of this compound Hs Antibody Binding - - -
⤷
BMS-986238 Peptide Hs Inhibitor Inhibition - - - 21
⤷ [21]
retlirafusp alfa Peptide Approved drug Hs Antibody Binding - - - 8,14
⤷ [8,14]
Targets where the ligand is described in the comment field
Target Comment
histone acetyltransferase 1 HAT1 lactylates target proteins such as replication protein A1 (RPA1) and programmed cell death 1 ligand 1 (CD274, Q9NZQ7) (PD-L1). This function impacts upon DNA repair and tumour immune evasion [22].
Ligand mentioned in the following text fields
CD molecules comments