CD274

Summary

CD274 (CD274 molecule, HGNC:17635) is a protein-coding gene on chromosome 9p24.1, encoding Programmed cell death 1 ligand 1 (Q9NZQ7). Plays a critical role in induction and maintenance of immune tolerance to self. In precision oncology, CD274 Expression confers sensitivity to Atezolizumab in Lung Non-small Cell Carcinoma (CIViC Level B); 11 further curated variant–drug associations are listed below.

This gene encodes an immune inhibitory receptor ligand that is expressed by hematopoietic and non-hematopoietic cells, such as T cells and B cells and various types of tumor cells. The encoded protein is a type I transmembrane protein that has immunoglobulin V-like and C-like domains. Interaction of this ligand with its receptor inhibits T-cell activation and cytokine production. During infection or inflammation of normal tissue, this interaction is important for preventing autoimmunity by maintaining homeostasis of the immune response. In tumor microenvironments, this interaction provides an immune escape for tumor cells through cytotoxic T-cell inactivation. Expression of this gene in tumor cells is considered to be prognostic in many types of human malignancies, including colon cancer and renal cell carcinoma. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 29126 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neonatal diabetes mellitus (Limited, GenCC)
• GWAS associations: 1
• Clinical variants (ClinVar): 30 total — 6 pathogenic
• GTEx eGene: eQTL in 28 tissues, sQTL in 0 (q < 0.05)
• Phenotypes (HPO): 16
• Drug target: yes — 13 curated mechanism-of-action drugs; 4 molecules with ChEMBL bioactivity
• Approved drugs (ChEMBL mechanism of action): 5 — Atezolizumab, Avelumab, Cosibelimab, +2 more
• Precision-oncology evidence (CIViC): 12 curated variant–drug associations
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 1 cancer types (inferred from mutation patterns)
• Constraint (gnomAD): pLI 0.98 (loss-of-function intolerant), LOEUF 0.48 (moderately constrained)
• MANE Select transcript: NM_014143
• Interaction hub: 5,398 STRING partners (top 1% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17635
Approved symbol	CD274
Name	CD274 molecule
Location	9p24.1
Locus type	gene with protein product
Status	Approved
Aliases	B7-H, B7H1, PD-L1, PDL1, B7-H1
Ensembl gene	ENSG00000120217
Ensembl biotype	protein_coding
OMIM	605402
Entrez	29126

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 3 protein_coding, 3 protein_coding_CDS_not_defined

MANE Select: ENST00000381577

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 2, TSL 5: 1

ENST00000381577, ENST00000381573, ENST00000474218, ENST00000492923, ENST00000498261, ENST00001133702

RefSeq mRNA: 2 — MANE Select: NM_014143 NM_001267706, NM_014143

CCDS: CCDS59118, CCDS6464

Canonical transcript exons

ENST00000381577 — 7 exons

Exon	Start	End
ENSE00000813155	5456100	5456165
ENSE00000813157	5462834	5463121
ENSE00000813158	5465499	5465606
ENSE00001889081	5467840	5470554
ENSE00001892659	5450542	5450596
ENSE00003507383	5466770	5466829
ENSE00003541119	5457079	5457420

Expression profiles

Bgee: expression breadth ubiquitous, 208 present calls, max score 88.56.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 18.7683 / max 968.8898, expressed in 1121 samples.

Highest expression (Bgee): cartilage tissue, placenta, lower lobe of lung, epithelial cell of pancreas, upper lobe of left lung.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CD274 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 28 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 28 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Pancreas	eqtl	9.8e-56	-0.96	9:5450953:C:T
Brain Cerebellar Hemisphere	eqtl	6.2e-23	+0.90	9:5453172:A:G
Esophagus Mucosa	eqtl	7.1e-23	-0.62	9:5450529:C:G
Whole Blood	eqtl	6.5e-20	+0.23	9:5466085:A:G
Adipose Subcutaneous	eqtl	9.9e-18	+0.42	9:5500129:C:G
Cells Cultured fibroblasts	eqtl	2.9e-14	+0.23	9:5500129:C:G
Brain Cerebellum	eqtl	2.2e-12	-0.63	9:5456550:T:C
Heart Atrial Appendage	eqtl	2.5e-12	-0.79	9:5506147:A:T
Nerve Tibial	eqtl	1.2e-10	+0.32	9:5500129:C:G
Brain Frontal Cortex BA9	eqtl	4.7e-09	+0.38	9:5450953:C:T
Lung	eqtl	2.6e-08	-0.49	9:5489171:G:A
Skin Sun Exposed Lower leg	eqtl	7.7e-08	+0.23	9:5490522:C:T
Artery Tibial	eqtl	8.0e-08	-0.41	9:5487791:G:A
Muscle Skeletal	eqtl	2.3e-07	-0.18	9:5456550:T:C
Heart Left Ventricle	eqtl	4.7e-06	-0.28	9:5509849:C:A
Testis	eqtl	3.6e-05	+0.43	9:5446078:A:G
Thyroid	eqtl	9.4e-05	-0.41	9:5491308:C:T
Brain Nucleus accumbens basal ganglia	eqtl	4.8e-04	+0.34	9:5453172:A:G
Skin Not Sun Exposed Suprapubic	eqtl	5.2e-04	+0.18	9:5498516:G:T
Cells EBV-transformed lymphocytes	eqtl	6.0e-04	+0.32	9:5878434:CTGTAAAAGGGG:C

FANTOM5 promoters

1 alternative TSS:

Promoter ID	TPM avg	Samples expressed
95944	18.7683	1121

Top tissues by expression

showing 100 of 245 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
cartilage tissue	UBERON:0002418	88.56	gold quality
placenta	UBERON:0001987	86.83	gold quality
lower lobe of lung	UBERON:0008949	86.80	gold quality
epithelial cell of pancreas	CL:0000083	86.75	gold quality
upper lobe of left lung	UBERON:0008952	85.84	gold quality
upper lobe of lung	UBERON:0008948	85.72	gold quality
right lung	UBERON:0002167	84.89	gold quality
left ventricle myocardium	UBERON:0006566	84.81	gold quality
vermiform appendix	UBERON:0001154	83.83	gold quality
pancreatic ductal cell	CL:0002079	83.03	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.44	gold quality
lung	UBERON:0002048	82.26	gold quality
heart right ventricle	UBERON:0002080	82.22	gold quality
myocardium	UBERON:0002349	81.56	gold quality
heart left ventricle	UBERON:0002084	81.30	gold quality
spleen	UBERON:0002106	81.26	gold quality
cardiac ventricle	UBERON:0002082	81.01	gold quality
ileal mucosa	UBERON:0000331	79.96	gold quality
heart	UBERON:0000948	77.79	gold quality
lymph node	UBERON:0000029	77.40	gold quality
tibialis anterior	UBERON:0001385	77.12	silver quality
apex of heart	UBERON:0002098	76.82	gold quality
blood	UBERON:0000178	76.43	gold quality
right atrium auricular region	UBERON:0006631	76.40	gold quality
thymus	UBERON:0002370	76.35	gold quality
cardiac atrium	UBERON:0002081	76.04	gold quality
stromal cell of endometrium	CL:0002255	75.58	gold quality
caecum	UBERON:0001153	75.53	gold quality
deltoid	UBERON:0001476	75.35	silver quality
gall bladder	UBERON:0002110	75.04	gold quality
islet of Langerhans	UBERON:0000006	74.47	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	74.22	gold quality
calcaneal tendon	UBERON:0003701	74.11	gold quality
visceral pleura	UBERON:0002401	73.93	gold quality
descending thoracic aorta	UBERON:0002345	73.17	gold quality
granulocyte	CL:0000094	72.99	gold quality
smooth muscle tissue	UBERON:0001135	72.95	gold quality
ascending aorta	UBERON:0001496	72.59	gold quality
thoracic aorta	UBERON:0001515	72.57	gold quality
hindlimb stylopod muscle	UBERON:0004252	72.42	gold quality
epithelium of nasopharynx	UBERON:0001951	72.18	gold quality
rectum	UBERON:0001052	71.41	gold quality
pancreas	UBERON:0001264	70.84	gold quality
muscle of leg	UBERON:0001383	70.74	gold quality
decidua	UBERON:0002450	70.67	gold quality
omental fat pad	UBERON:0010414	70.45	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	70.38	gold quality
peritoneum	UBERON:0002358	70.37	gold quality
right coronary artery	UBERON:0001625	70.30	gold quality
tonsil	UBERON:0002372	69.78	gold quality
body of pancreas	UBERON:0001150	69.71	gold quality
esophagus mucosa	UBERON:0002469	69.67	gold quality
nasal cavity epithelium	UBERON:0005384	69.60	silver quality
gastrocnemius	UBERON:0001388	69.55	gold quality
leukocyte	CL:0000738	69.35	gold quality
right lobe of liver	UBERON:0001114	69.33	gold quality
pituitary gland	UBERON:0000007	69.29	gold quality
right uterine tube	UBERON:0001302	69.13	gold quality
adenohypophysis	UBERON:0002196	69.07	gold quality
left lobe of thyroid gland	UBERON:0001120	69.00	gold quality
adipose tissue of abdominal region	UBERON:0007808	68.96	gold quality
monocyte	CL:0000576	68.77	gold quality
tendon	UBERON:0000043	68.62	gold quality
thyroid gland	UBERON:0002046	68.56	gold quality
palpebral conjunctiva	UBERON:0001812	68.53	gold quality
endothelial cell	CL:0000115	68.06	gold quality
buccal mucosa cell	CL:0002336	68.06	silver quality
aorta	UBERON:0000947	68.04	gold quality
muscle tissue	UBERON:0002385	67.82	gold quality
right lobe of thyroid gland	UBERON:0001119	67.75	gold quality
left coronary artery	UBERON:0001626	67.72	gold quality
esophagus	UBERON:0001043	67.70	gold quality
esophagus squamous epithelium	UBERON:0006920	67.63	gold quality
ectocervix	UBERON:0012249	67.63	gold quality
upper arm skin	UBERON:0004263	67.52	gold quality
mucosa of stomach	UBERON:0001199	67.27	gold quality
small intestine Peyer’s patch	UBERON:0003454	67.20	gold quality
metanephros cortex	UBERON:0010533	67.12	gold quality
subcutaneous adipose tissue	UBERON:0002190	67.06	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	66.86	gold quality
coronary artery	UBERON:0001621	66.43	gold quality
endocervix	UBERON:0000458	66.24	gold quality
small intestine	UBERON:0002108	66.21	gold quality
bone marrow cell	CL:0002092	66.19	silver quality
body of uterus	UBERON:0009853	66.11	gold quality
skeletal muscle tissue	UBERON:0001134	66.05	gold quality
nasal cavity mucosa	UBERON:0001826	65.81	gold quality
hypothalamus	UBERON:0001898	65.81	gold quality
lower esophagus muscularis layer	UBERON:0035833	65.62	gold quality
bronchial epithelial cell	CL:0002328	65.58	gold quality
lower esophagus	UBERON:0013473	65.57	gold quality
biceps brachii	UBERON:0001507	65.25	silver quality
popliteal artery	UBERON:0002250	64.82	gold quality
liver	UBERON:0002107	64.76	gold quality
tibial artery	UBERON:0007610	64.76	gold quality
parietal pleura	UBERON:0002400	64.67	gold quality
bronchus	UBERON:0002185	64.65	gold quality
minor salivary gland	UBERON:0001830	64.48	gold quality
anatomical system	UBERON:0000467	64.42	gold quality
duodenum	UBERON:0002114	64.37	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	13.14
E-MTAB-8498	yes	10.17

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 76 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Thymus	tissue	12.1	high
Appendix	tissue	9.7	medium
Heart muscle	tissue	8.3	not detected
Spleen	tissue	8.2	not detected
Urinary bladder	tissue	6.7
Placenta	tissue	6.4	high
Lung	tissue	6.4	medium
Lymph node	tissue	6.1	low
Tonsil	tissue	5.0	medium
Substantia nigra	tissue	4.9
Parathyroid gland	tissue	4.7	not detected
Hypothalamus	tissue	4.5
Skeletal muscle	tissue	4.3	not detected
Tongue	tissue	4.1
Periaqueductal gray	tissue	4.1
Gallbladder	tissue	3.8	not detected
Olfactory bulb	tissue	3.7
Pons	tissue	3.5
Cerebellum	tissue	3.5	not detected
Septum	tissue	3.4
Thyroid gland	tissue	3.3	not detected
Liver	tissue	3.2	not detected
Locus coeruleus	tissue	3.2
Amygdala	tissue	3.1
Midbrain	tissue	3.0
Ventral forebrain	tissue	3.0
Cerebral cortex	tissue	2.8	not detected
Insular cortex	tissue	2.8
Spinal cord	tissue	2.7
Hippocampal formation	tissue	2.7
Retrosplenial cortex	tissue	2.7
Basal ganglia	tissue	2.6	not detected
Entorhinal cortex	tissue	2.6
Retrosplenial and cingulate cortex	tissue	2.6
Temporal cortex	tissue	2.6
Occipital cortex	tissue	2.6
Pituitary gland	tissue	2.5
Prefrontal cortex	tissue	2.5
Putamen	tissue	2.5
Duodenum	tissue	2.5	not detected
Medulla oblongata	tissue	2.4
Superior colliculi	tissue	2.4
Esophagus	tissue	2.3	not detected
Corpus callosum	tissue	2.3
Somatosensory cortex	tissue	2.3
Thalamus	tissue	2.2
Postcentral gyrus	tissue	2.2
Smooth muscle	tissue	2.1	not detected
Motor cortex	tissue	2.1
Rectum	tissue	2.0	not detected
Adrenal gland	tissue	1.9	not detected
Stomach 1	tissue	1.8	not detected
Small intestine	tissue	1.8	not detected
Bone marrow	tissue	1.8	not detected
Cervix	tissue	1.7	not detected
Epididymis	tissue	1.7	not detected
Fallopian tube	tissue	1.7	not detected
Adipose tissue	tissue	1.5	not detected
Nucleus accumbens	tissue	1.5
Seminal vesicle	tissue	1.4	not detected

Brain sub-regions (HPA Brain Atlas): detected in 190; highest nTPM — Spinal trigeminal nucleus, oral (3.9), Supraoptic nucleus (3.8), Arcuate nucleus (3.6), Parvicellular reticular nuclei, medullary (3.5), Peritrigeminal nucleus (3.5).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOXA1, HIF1A, IRF1, KMT2C, NFKB, STAT1, STAT3

miRNA regulators (miRDB)

Targeting CD274 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 141 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-570-3P	99.96	72.41	4910
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502

Functional genomics

gnomAD constraint: pLI 0.982, LOEUF 0.476, missense Z 0.449 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000381577 — one region, missense o/e 1.02.

Literature-anchored findings (GeneRIF, showing 40)

• Cancer cell-associated B7-H1 increases apoptosis of antigen-specific human T-cell clones in vitro (PMID:12091876)
• B7-H1 is inducible on human endothelial cells by IFN-gamma both in vitro and in vivo; blocking its interaction with its receptor (PD-1) on T cells augments T cell cytokine synthesis. (PMID:12244148)
• up-regulation in HIV infection, relation to disease progression, and possible role in AIDS progression (PMID:12468426)
• Blockade of PD-L1 during T cell responses initiated by allogenic dendritic cells increases T cell proliferation and cytokine production, showing that PD-L1 functions to inhibit T cell activation. (PMID:12538684)
• Monoclonal antibody DF272-defined surface molecule B7-H1 represents a unique receptor structure on dendritic cells that may play a role in the induction and maintenance of T cell anergy. (PMID:12646628)
• binding properties of B7-H1 to programmed death-1. (PMID:12893276)
• B7-H1 is expressed in muscle cells and may have a negative immune regulatory function in idiopathic inflammatory myopathies. (PMID:12923066)
• review of the negative immunoregulatory role of B7-H1 documented in human diseases, including cancer and auotimmune diseases (PMID:14686489)
• Inflammatory bowel disease intestinal epithelial cell (IEC) surface expressed B7h and B7-H1. Proliferation of IEC-stimulated T cells was inhibited only by B7h immunoglobulin. Interferon gamma was inhibited by both anti-B7h mAb and B7h Ig. (PMID:15131796)
• B7-H1 may have a role in antitumor immune responses in non-small cell lung cancer (PMID:15297412)
• IFN-beta up-regulates B7-H1 in vitro and in MS patients in vivo and might represent a novel mechanism how IFN-beta acts as a negative modulator on APC T-cell interactions in the periphery. (PMID:15342209)
• Data suggest that PD-L1 status may be a new predictor of prognosis for patients with esophageal cancer. (PMID:15837746)
• B7 homolog 1 (B7H1) may be involved in the immune evasion of human glioma (PMID:15973152)
• Inhibitory signals delivered from human rhinovirus HRV14-treated dendritic cells to T cells via B7-H1 are critical for induction of T-cell anergy. (PMID:16002716)
• dermal fibroblasts express the B7-H1 mRNA in the process of skin inflammation, suggesting the involvement of NF-kappaB and MAPK and PI3K (PMID:16085391)
• Interaction of tubular epithelial cells and kidney infiltrating T cells via ICOS-L and B7-H1 may change the balance of positive and negative signals to the T cells (PMID:16221208)
• dysfunction of the PD-1/PD-L1 pathway may be related to tolerance for lymphocytes, which causes Sjogren syndrome (PMID:16265694)
• B7-H1 is inducible renal tubular epithelial antigen that inhibits T cell activation. B7-H1/PD-1 pathway might play role in protecting tubular epithelium from immune-mediated damage. B7-H1 may be therapeutic strategy in autoimmune renal diseases. (PMID:16282703)
• Our data suggest that PD-L1/PD-1 interactions negatively regulate T cell effector functions predominantly in the absence of exogenous cytokine support, indicating an important role for this pathway in tumor evasion. (PMID:16482562)
• B7-H1 is involved in suppression of T cell proliferation and IL-2 synthesis, roles suggested for B7-H1 on the gastric epithelium that contribute to the chronicity of Helicobacter pylori infection. (PMID:16493058)
• Multivariate analysis demonstrated that PD-L1 immunodetection could be used as an independent factor to evaluate the prognosis of gastric carcinoma. (PMID:16530813)
• a novel bidirectional interaction between hepatocytes and lymphocytes modulated by PD-L1 expression in hepatocytes may contribute to the unique immunological properties of the liver (PMID:16876901)
• Overexpression reduces accessory immune functions of endothelial cells. (PMID:16916652)
• data do not support an association between systemic lupus erythematosus and SNP’s within the genes of the PDCD1 ligands PD-L1 and PD-L2 (PMID:17136123)
• The aberrant expression of B7-H1 in urothelial cancer is associated with aggressive tumors, suggesting a regulatory role of tumor-associated B7-H1 in antitumor immunity. (PMID:17186290)
• Modulation of PD-L1 system may play a role in the development of autoimmune liver diseases. (PMID:17311651)
• Programmed cell death 1 ligand 1 and tumor-infiltrating CD8+ T lymphocytes are prognostic factors of human ovarian cancer. (PMID:17360651)
• Inhibition of the MyD88 and TRAF6 adaptor proteins of the TLR pathway blocked not only B7-H1 expression induced by TLR ligands but also that mediated by IFN-gamma (PMID:17363736)
• Data show that sPD-Ll and its antibodies provide the basis for detection of the potential anti-PD-L1 antibodies and soluble PD-L1 in humans as well as for further investigation of its in vivo bioactivities and characterization of its potential receptors. (PMID:17366897)
• B7-H1 was downregulated in quiescent cells and upregulated in cells stimulated with a mitogen confirming the association of proliferation with the induction of B7-H1. (PMID:17415709)
• Elevated B7-H1 expression is closely associated with the suppression of T cell immune function in chronic hepatitis B patients. (PMID:17475895)
• Induction of cells of the T regulatory (Treg) phenotype by B7-H1 may play an important role in the T-cell suppression associated with Helicobacter pylori infection, as well as other infections that result in an up-regulation of B7-H1. (PMID:17562772)
• PD-L1 polymorphisms are not associated with susceptibility to rheumatoid arthritis, but 6777 G is associated with the prevalence of rheumatoid nodule in Taiwanese patients. (PMID:17597384)
• results indicate Hepatitis C virus core can upregulate a key negative T cell signaling pathway, PD-1/PDL-1, associated with viral persistence & expressed on T cells of infected individuals (PMID:17603844)
• chemopreventive agents were able to induce PD-L1 surface expression in human breast cancer cells, which then promoted PD-L1-mediated T cell apoptosis, a potential link between chemotherapy and cancer immunoresistance (PMID:17920123)
• PD-L1-deficient transgenic mice reconstituted with bone marrow from wild-type mice remain susceptible to severe myocarditis, demonstrating the protective effect of PD-L1 on non-bone marrow-derived cells. (PMID:17938288)
• results suggest that the PD-1/PD-L1 pathway may play a regulatory role in memory T cell subsets in addition to its association with T-cell exhaustion (PMID:17942371)
• B7-H1 and PD-1 expressions in patients with chronic hepatitis B are closely associated with their disease status. (PMID:17963598)
• There is no significant difference in B7-H1 expression on T cells and B cells between chronic hepatitis B patients and healthy subjects. (PMID:18024277)
• Blockade of the B7-H1 pathway may represent an attractive approach in the treatment of chronic hepatitis C. (PMID:18086898)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cd274	ENSMUSG00000016496
rattus_norvegicus	Cd274	ENSRNOG00000016112

Paralogs (12): CD86 (ENSG00000114013), CD80 (ENSG00000121594), RFPL1 (ENSG00000128250), RFPL2 (ENSG00000128253), RFPL3 (ENSG00000128276), SPRYD4 (ENSG00000176422), RNF152 (ENSG00000176641), RNF135 (ENSG00000181481), PDCD1LG2 (ENSG00000197646), RFPL4A (ENSG00000223638), RFPL4AL1 (ENSG00000229292), RFPL4B (ENSG00000251258)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1926446) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 42 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal cytokine secretion	2
abnormal CD8-positive, alpha-beta T cell physiology	2
increased susceptibility to experimental autoimmune encephalomyelitis	2
decreased T cell apoptosis	2
increased CD8-positive, alpha-beta T cell number	2
increased interferon-gamma secretion	2
increased activated T cell number	1
abnormal dendritic cell physiology	1
increased susceptibility to bacterial infection	1
abnormal CD4-positive, alpha beta T cell morphology	1
hyperresponsive to tactile stimuli	1
increased susceptibility to induced arthritis	1
increased susceptibility to autoimmune diabetes	1
abnormal regulatory T cell physiology	1
abnormal CD8-positive, alpha beta T cell morphology	1
increased T cell number	1
decreased susceptibility to parasitic infection	1
increased susceptibility to injury	1
increased T cell proliferation	1
increased susceptibility to autoimmune disorder	1
abnormal T cell morphology	1
decreased CD8-positive, alpha-beta T cell number	1
decreased T helper 1 cell number	1
abnormal T-helper 1 cell differentiation	1
decreased plasma cell number	1

+17 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Gallus gallus	Q589G5	85.5%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
INCR1	ncRNA	124902114
PLGRKT	protein-coding	55848
RLN1	protein-coding	6013
RLN2	protein-coding	6019
PDCD1LG2	protein-coding	80380
RIC1	protein-coding	57589
ERMP1	protein-coding	79956
BRD10	protein-coding	158358
INSL4	protein-coding	3641
INSL6	protein-coding	11172
JAK2	protein-coding	3717

Protein

Protein identifiers

Programmed cell death 1 ligand 1 — Q9NZQ7 (reviewed: Q9NZQ7)

Alternative names: B7 homolog 1

All UniProt accessions (1): Q9NZQ7

UniProt curated annotations — full annotation on UniProt →

Function. Plays a critical role in induction and maintenance of immune tolerance to self. As a ligand for the inhibitory receptor PDCD1/PD-1, modulates the activation threshold of T-cells and limits T-cell effector response. Through a yet unknown activating receptor, may costimulate T-cell subsets that predominantly produce interleukin-10 (IL10). Can also act as a transcription coactivator: in response to hypoxia, translocates into the nucleus via its interaction with phosphorylated STAT3 and promotes transcription of GSDMC, leading to pyroptosis. The PDCD1-mediated inhibitory pathway is exploited by tumors to attenuate anti-tumor immunity and escape destruction by the immune system, thereby facilitating tumor survival. The interaction with PDCD1/PD-1 inhibits cytotoxic T lymphocytes (CTLs) effector function. The blockage of the PDCD1-mediated pathway results in the reversal of the exhausted T-cell phenotype and the normalization of the anti-tumor response, providing a rationale for cancer immunotherapy.

Subunit / interactions. Interacts with PDCD1. Interacts (via transmembrane domain) with CMTM4 and CMTM6. Interacts with (phosphorylated) STAT3; promoting nuclear translocation. Interacts with CD80. May form homomultimers.

Subcellular location. Cell membrane. Early endosome membrane. Recycling endosome membrane. Nucleus Cell membrane Endomembrane system Secreted.

Tissue specificity. Highly expressed in the heart, skeletal muscle, placenta and lung. Weakly expressed in the thymus, spleen, kidney and liver. Expressed on activated T- and B-cells, dendritic cells, keratinocytes and monocytes. Widely expressed, highest in lung, liver and pituitary and in various peripheral blood cells, including neutrophils and some subtypes of lymphoid and myeloid cells.

Post-translational modifications. Ubiquitinated; STUB1 likely mediates polyubiquitination of PD-L1/CD274 triggering its degradation. Ubiquitinated by MARCHF8; leading to degradation. Deubiquitinated by USP22; leading to stabilization.

Disease relevance. Autoimmune disease, multisystem, infantile-onset, 5 (ADMIO5) [MIM:621235] An autosomal recessive disorder characterized by autoimmune manifestations apparent in the first months or years of life. ADMIO5 patients have complete insulin deficiency and type 1 diabetes mellitus with neonatal onset. The disease is caused by variants affecting the gene represented in this entry. Truncation of the 3’-untranslated (3’-UTR) region of CD274 transcripts leads to elevated expression of CD274 in multiple cancers including T-cell leukemia, diffuse large B-cell lymphoma and stomach adenocarcinoma. Disruption of 3’-UTR region is caused by structural variants that stabilize CD274 transcripts, leading to overexpression. Increased expression in tumors promotes immune evasion and tumor cell growth by allowing malignant cells to escape destruction by the immune system.

Induction. Up-regulated on T- and B-cells, dendritic cells, keratinocytes and monocytes after LPS and IFNG activation. Up-regulated in B-cells activated by surface Ig cross-linking.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Similarity. Belongs to the immunoglobulin superfamily. BTN/MOG family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q9NZQ7-1	1, PD-L1I	yes
Q9NZQ7-2	2, PD-L1II
Q9NZQ7-3	3
Q9NZQ7-4	4, secPD-L1

RefSeq proteins (2): NP_001254635, NP_054862* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003599	Ig_sub	Domain
IPR007110	Ig-like_dom	Domain
IPR013106	Ig_V-set	Domain
IPR013162	CD80_C2-set	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR051713	T-cell_Activation_Regulation	Family

Pfam: PF07686, PF08205

UniProt features (46 total): strand 17, helix 7, glycosylation site 4, splice variant 4, turn 4, disulfide bond 2, topological domain 2, domain 2, signal peptide 1, chain 1, transmembrane region 1, mutagenesis site 1

Structure

Experimental structures (PDB)

showing 30 of 78 structures by resolution:

PDB	Title	Method	Resolution (Å)
5O45	Structure of human PD-L1 in complex with inhibitor	X-RAY DIFFRACTION	0.99
8ALX	Structure of human PD-L1 in complex with inhibitor	X-RAY DIFFRACTION	1.1
6NP9	PD-L1 IgV domain V76T with fragment	X-RAY DIFFRACTION	1.27
9I0U	Structure of human PD-L1 in complex with clinically evaluated inhibitor	X-RAY DIFFRACTION	1.46
6YCR	Structure of human PD-L1 in complex with inhibitor	X-RAY DIFFRACTION	1.54
8AOK	Complex of PD-L1 with VHH6	X-RAY DIFFRACTION	1.6
7CZD	Crystal structure of PD-L1 in complex with a VHH	X-RAY DIFFRACTION	1.64
5JDS	Crystal structure of PD-L1 complexed with a nanobody at 1.7 Angstron resolution	X-RAY DIFFRACTION	1.7
5N2F	Structure of PD-L1/small-molecule inhibitor complex	X-RAY DIFFRACTION	1.7
9QSM	small molecule inhibitor in complex with PD-L1	X-RAY DIFFRACTION	1.75
8ZNL	PD-L1 de novo designed binder with picomolar binding affinity	X-RAY DIFFRACTION	1.77
5C3T	PD-1 binding domain from human PD-L1	X-RAY DIFFRACTION	1.8
7OUN	Structure of human PD-L1 in complex with macrocyclic inhibitor	X-RAY DIFFRACTION	1.9
6NNV	PD-L1 IgV domain complex with macro-cyclic peptide	X-RAY DIFFRACTION	1.92
8XR5	Crystal structure of PD-L1 complexed with small molecule inhibitor X18	X-RAY DIFFRACTION	1.95
4Z18	CRYSTAL STRUCTURE OF HUMAN PD-L1	X-RAY DIFFRACTION	1.95
7C88	Complex structure of JS003 and PD-L1	X-RAY DIFFRACTION	2
6PV9	Human PD-L1 bound to a macrocyclic peptide which blocks the PD-1/PD-L1 interaction	X-RAY DIFFRACTION	2
7SJQ	Ex silico engineering of cystine-dense peptides yielding a potent bispecific T-cell …	X-RAY DIFFRACTION	2
5NIU	Structure of human Programmed cell death 1 ligand 1 (PD-L1) with low molecular mass …	X-RAY DIFFRACTION	2.01
9IJT	Crystal Structure of human Programmed cell death 1 ligand 1 (PD-L1) bound to Small …	X-RAY DIFFRACTION	2.05
9I0W	Structure of human PD-L1 in complex with clinically evaluated inhibitor	X-RAY DIFFRACTION	2.1
8P1O	Solubilizer tag effect on PD-L1/inhibitor binding properties for m-terphenyl derivatives	X-RAY DIFFRACTION	2.17
5J89	Structure of human Programmed cell death 1 ligand 1 (PD-L1) with low molecular mass …	X-RAY DIFFRACTION	2.2
6R3K	Structure of human Programmed cell death 1 ligand 1 (PD-L1) with low molecular mass …	X-RAY DIFFRACTION	2.2
8K5N	Discovery of Novel PD-L1 Inhibitors That Induce Dimerization and Degradation of PD-L1 …	X-RAY DIFFRACTION	2.2
8AOM	Complex of PD-L1 with VHH1	X-RAY DIFFRACTION	2.2
13FL	Structure of FabS1CE2_P2a in complex with the N-terminal domain of PD-L1	X-RAY DIFFRACTION	2.22
7UXO	Structure of PDL1 in complex with FP30790, a Helicon Polypeptide	X-RAY DIFFRACTION	2.25
3SBW	Crystal structure of the complex between the extracellular domains of mouse PD-1 mutant …	X-RAY DIFFRACTION	2.28

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NZQ7-F1	88.13	0.70

Antibody-complex structures (SAbDab)

19 antibodies co-crystallized with this protein: 5GGT, 5GRJ, 5JDS, 5X8L, 5X8M, 5XJ4, 5XXY, 7C88, 7CZD, 7YDS, 8AOK, 8AOM, 8RPB, ATEZOLIZUMAB, DURVALUMAB, ITANISTOMIG, PALVERAFUSP, PUMITAMIG2, SUDUBRILIMAB

Human Protein Atlas

Protein class: CD markers, Transporters, Accessory Factors Involved in Transport, Predicted membrane proteins, Predicted secreted proteins, Cancer-related genes, Disease related genes, FDA approved drug targets, Biotech drugs

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nuclear speckles; nucleoplasm; plasma membrane

Antibody reliability (HPA): IH enhanced · IF supported

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Disulfide bonds (2)

Type	Positions
Disulfide bond	40–114, 155–209

Glycosylation sites (4)

Type	Positions
N-linked (glcnac…) asparagine	219, 35, 192, 200

Mutagenesis-validated functional residues (1)

Position	Phenotype
238	largely abrogates multimerization, in vitro.

Function

Pathways and Gene Ontology

Reactome pathways

8 curated (TAS) of 14; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

14 pathways:

ID	Pathway	Evidence
R-HSA-9931269	AMPK-induced ERAD and lysosome mediated degradation of PD-L1(CD274)	curated
R-HSA-389948	Co-inhibition by PD-1	curated
R-HSA-9929356	GSK3B-mediated proteasomal degradation of PD-L1(CD274)	curated
R-HSA-9931295	PD-L1(CD274) glycosylation and translocation to plasma membrane	curated
R-HSA-9909649	Regulation of PD-L1(CD274) transcription	curated
R-HSA-9909620	Regulation of PD-L1(CD274) translation	curated
R-HSA-9929491	SPOP-mediated proteasomal degradation of PD-L1(CD274)	curated
R-HSA-9701898	STAT3 nuclear events downstream of ALK signaling	curated
R-HSA-1280218	Adaptive Immune System	—
R-HSA-168256	Immune System	—
R-HSA-388841	Regulation of T cell activation by CD28 family	—
R-HSA-162582	Signal Transduction	—
R-HSA-201556	Signaling by ALK	—
R-HSA-9006934	Signaling by Receptor Tyrosine Kinases	—

MSigDB gene sets: 442 (showing top): GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_DN, GOBP_REGULATION_OF_T_CELL_RECEPTOR_SIGNALING_PATHWAY, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_REGULATION_OF_ANTIGEN_RECEPTOR_MEDIATED_SIGNALING_PATHWAY, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_POSITIVE_REGULATION_OF_LYMPHOCYTE_APOPTOTIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GOBP_REGULATION_OF_ALPHA_BETA_T_CELL_ACTIVATION, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_POSITIVE_REGULATION_OF_LEUKOCYTE_APOPTOTIC_PROCESS, GOBP_RESPONSE_TO_PEPTIDE, GOBP_REGULATION_OF_LEUKOCYTE_APOPTOTIC_PROCESS, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_NEGATIVE_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE

GO Biological Process (23): adaptive immune response (GO:0002250), negative regulation of T cell mediated immune response to tumor cell (GO:0002841), immune response (GO:0006955), signal transduction (GO:0007165), cell surface receptor signaling pathway (GO:0007166), T cell costimulation (GO:0031295), negative regulation of type II interferon production (GO:0032689), negative regulation of interleukin-10 production (GO:0032693), positive regulation of interleukin-10 production (GO:0032733), response to cytokine (GO:0034097), TRIF-dependent toll-like receptor signaling pathway (GO:0035666), positive regulation of T cell proliferation (GO:0042102), negative regulation of T cell proliferation (GO:0042130), negative regulation of activated T cell proliferation (GO:0046007), negative regulation of T cell receptor signaling pathway (GO:0050860), negative regulation of T cell activation (GO:0050868), cellular response to lipopolysaccharide (GO:0071222), negative regulation of tumor necrosis factor superfamily cytokine production (GO:1903556), positive regulation of activated CD8-positive, alpha-beta T cell apoptotic process (GO:1905404), negative regulation of CD4-positive, alpha-beta T cell proliferation (GO:2000562), negative regulation of CD8-positive, alpha-beta T cell activation (GO:2001186), immune system process (GO:0002376), positive regulation of DNA-templated transcription (GO:0045893)

GO Molecular Function (3): transcription coactivator activity (GO:0003713), receptor ligand activity (GO:0048018), protein binding (GO:0005515)

GO Cellular Component (12): Golgi membrane (GO:0000139), nucleoplasm (GO:0005654), endoplasmic reticulum membrane (GO:0005789), cytosol (GO:0005829), plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), nuclear speck (GO:0016607), early endosome membrane (GO:0031901), recycling endosome membrane (GO:0055038), extracellular exosome (GO:0070062), extracellular region (GO:0005576), endomembrane system (GO:0012505)

Reactome top-level categories

8 top-level categories:

Category	Pathways
Regulation of PD-L1(CD274) Post-translational modification	4
Regulation of PD-L1(CD274) expression	2
Regulation of T cell activation by CD28 family	1
Signaling by ALK	1
Immune System	1
Signaling by Receptor Tyrosine Kinases	1
Adaptive Immune System	1
Signal Transduction	1

GO top-level categories

showing 60 of 75 GO namespaces:

Category	Terms
cellular anatomical structure	4
negative regulation of cytokine production	3
signal transduction	2
positive regulation of T cell activation	2
interleukin-10 production	2
regulation of interleukin-10 production	2
T cell proliferation	2
regulation of T cell proliferation	2
plasma membrane	2
endosome membrane	2
immune response	1
T cell mediated immune response to tumor cell	1
negative regulation of T cell mediated immunity	1
negative regulation of immune response to tumor cell	1
regulation of T cell mediated immune response to tumor cell	1
immune system process	1
response to stimulus	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
lymphocyte costimulation	1
type II interferon production	1
regulation of type II interferon production	1
positive regulation of cytokine production	1
response to peptide	1
MyD88-independent toll-like receptor signaling pathway	1
positive regulation of lymphocyte proliferation	1
negative regulation of lymphocyte proliferation	1
negative regulation of T cell activation	1
negative regulation of T cell proliferation	1
regulation of activated T cell proliferation	1
activated T cell proliferation	1
T cell receptor signaling pathway	1
regulation of T cell receptor signaling pathway	1
negative regulation of antigen receptor-mediated signaling pathway	1
T cell activation	1
regulation of T cell activation	1
negative regulation of lymphocyte activation	1
negative regulation of leukocyte cell-cell adhesion	1
response to lipopolysaccharide	1
cellular response to molecule of bacterial origin	1
cellular response to lipid	1
cellular response to oxygen-containing compound	1
tumor necrosis factor superfamily cytokine production	1
regulation of tumor necrosis factor superfamily cytokine production	1
positive regulation of T cell apoptotic process	1
activated CD8-positive, alpha-beta T cell apoptotic process	1
regulation of activated CD8-positive, alpha-beta T cell apoptotic process	1
CD4-positive, alpha-beta T cell proliferation	1
negative regulation of alpha-beta T cell proliferation	1
negative regulation of CD4-positive, alpha-beta T cell activation	1
regulation of CD4-positive, alpha-beta T cell proliferation	1
transcription coregulator activity	1
positive regulation of DNA-templated transcription	1
signaling receptor binding	1
signaling receptor activator activity	1
binding	1
Golgi apparatus	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 25 of 38 annotations. The rest are phylogenetic / computational / electronic (IEA).

25 experimentally-supported GO terms:

GO term	NS	Evidence
T cell costimulation	BP	direct assay
TRIF-dependent toll-like receptor signaling pathway	BP	direct assay
cell surface receptor signaling pathway	BP	direct assay
immune response	BP	direct assay
negative regulation of CD4-positive, alpha-beta T cell proliferation	BP	direct assay
negative regulation of CD8-positive, alpha-beta T cell activation	BP	direct assay
negative regulation of T cell activation	BP	direct assay
negative regulation of T cell mediated immune response to tumor cell	BP	direct assay
negative regulation of T cell receptor signaling pathway	BP	direct assay
negative regulation of activated T cell proliferation	BP	mutant phenotype
negative regulation of interleukin-10 production	BP	mutant phenotype
negative regulation of tumor necrosis factor superfamily cytokine production	BP	mutant phenotype
negative regulation of type II interferon production	BP	mutant phenotype
positive regulation of activated CD8-positive, alpha-beta T cell apoptotic process	BP	direct assay
positive regulation of interleukin-10 production	BP	direct assay
response to cytokine	BP	direct assay
signal transduction	BP	direct assay
early endosome membrane	CC	direct assay
extracellular exosome	CC	direct assay
nuclear speck	CC	direct assay
nucleoplasm	CC	direct assay
plasma membrane	CC	direct assay
recycling endosome membrane	CC	direct assay
receptor ligand activity	MF	direct assay
transcription coactivator activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 5,398 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CD274	PDCD1	Q15116	973
CD274	CTLA4	P16410	966
CD274	CD8A	P01732	946
CD274	CD28	P10747	925
CD274	CD4	P01730	918
CD274	IFNG	P01579	890
CD274	ICOS	Q9Y6W8	884
CD274	LAG3	P18627	882
CD274	HAVCR2	Q8TDQ0	882
CD274	IDO1	P14902	881
CD274	EGFR	P00533	880
CD274	IL10	P22301	864
CD274	FOXP3	Q9BZS1	859
CD274	TIGIT	Q495A1	859
CD274	ALK	Q9UM73	857

IntAct

Human interaction partners of CD274 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

11 partners by confidence:

Partner	Interaction type	MIscore	Records
CD80	direct interaction	0.950	11
PDCD1	direct interaction	0.890	19
PDCD1LG2	association	0.740	3
CMTM6	physical association	0.690	10
PEX19	association	0.530	1
TTI1	association	0.530	1
CMTM4	association	0.500	2
CTLA4	physical association	0.400	1
NCR3	physical association	0.400	1
ORC4	association	0.350	1
TNPO2	association	0.350	1

BioGRID (557 interactions; top human partners by supporting records): USP22 (Affinity Capture-MS; 9 records), SPOP (Affinity Capture-Western; 8 records), ATR (Affinity Capture-MS; 5 records), HUWE1 (Affinity Capture-MS; 5 records), IPO7 (Affinity Capture-MS; 5 records), TMUB1 (Affinity Capture-MS; 5 records), USP5 (Affinity Capture-MS; 5 records), USP7 (Affinity Capture-Western; 5 records), ATM (Affinity Capture-MS; 4 records), MIB2 (Affinity Capture-Western; 4 records), MTOR (Affinity Capture-MS; 4 records), OTUB1 (Affinity Capture-Western; 4 records), PDCD1 (Reconstituted Complex; 4 records), RNF125 (Affinity Capture-Western; 4 records), TNPO3 (Affinity Capture-MS; 4 records)

SIGNOR signaling

showing 23 of 26 signaling interactions:

A	Effect	B	Mechanism
HIF1A	“up-regulates quantity by expression”	CD274	“transcriptional regulation”
STAT3	“up-regulates quantity by expression”	CD274	“transcriptional regulation”
KMT2C	“up-regulates quantity by expression”	CD274	“transcriptional regulation”
FKBP5	“up-regulates quantity by expression”	CD274	“catalytic activity”
SIGMAR1	“up-regulates quantity by stabilization”	CD274	stabilization
STT3A	“up-regulates quantity by stabilization”	CD274	glycosylation
STT3B	“up-regulates quantity by stabilization”	CD274	glycosylation
COPS5	“up-regulates quantity by stabilization”	CD274	deubiquitination
SPOP	“down-regulates quantity”	CD274	ubiquitination
STUB1	“down-regulates quantity by destabilization”	CD274	destabilization
CMTM6	“up-regulates quantity by stabilization”	CD274	stabilization
CMTM4	“up-regulates quantity by stabilization”	CD274	stabilization
B3GNT3	“up-regulates activity”	CD274	glycosylation
GSK3B	“down-regulates quantity by destabilization”	CD274	phosphorylation
SCF-betaTRCP	“down-regulates quantity by destabilization”	CD274	polyubiquitination
GSK3A	“down-regulates quantity by destabilization”	CD274	phosphorylation
ARIH1	“down-regulates quantity by destabilization”	CD274	polyubiquitination
FOXP3	“up-regulates quantity by expression”	CD274	“transcriptional regulation”
ARIH1	“down-regulates quantity by destabilization”	CD274	ubiquitination
ITCH	“down-regulates quantity by destabilization”	CD274	ubiquitination
GSK3B	“down-regulates quantity”	CD274	phosphorylation
CD274	up-regulates	PDCD1	binding
NEK2	“up-regulates quantity by stabilization”	CD274	phosphorylation

Protein complexes (CORUM) (5)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

5 complexes by size:

Complex	Subunits	Members
★ CD274-RAB11A-TRAPPC4 complex	3	CD274, RAB11A, TRAPPC4
★ CD274-PDCD1 complex	2	CD274, PDCD1
★ CD274-STAT3 complex	2	CD274, STAT3
★ CD274-CMTM4 complex	2	CD274, CMTM4
★ CD274-CMTM6 complex	2	CMTM6, CD274

Ligand–receptor pairs (CellPhoneDB) (2)

Curated ligand–receptor partners (cell-cell communication), distinct from the protein–protein interactions above.

2 ligand–receptor pairs:

Partner	This gene’s role	Signaling class
PDCD1	ligand
CD80	ligand

Disease & clinical

Cancer significance

From CIViC — curated cancer-variant interpretation:

CD274, also commonly referred to as PDL1, is a ligand that binds with the receptor PD1, commonly found on T-cells, and acts to block T-cell activation. PD1 expression has been observed in a variety of cancers including melanoma and non-small cell lung cancer. The interaction of PD1/PDL1 is hypothesized to be a possible mechanism for the tumor to escape immune response. A number of checkpoint blockade inhibitors including pembrolizumab and nivolumab have been developed that target the PD1/PDL1 interaction in order to allow T-cells to recognize tumor cells without being deactivated by the tumor.

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 1 cancer types — DLBCLNOS.

intOGen’s role is a computational inference from cohort mutation patterns and may diverge from the gene’s curated/literature role; read it alongside the evidence above.

Genetic variants

Variant evidence for CD274: 30 ClinVar records (6 pathogenic / likely pathogenic); 1 CIViC cancer variant; 1 GWAS association. Per-variant detail is on Sugi Variant.

ClinVar

30 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	6
Likely pathogenic	0
Uncertain significance	13
Likely benign	2
Benign	5

Top pathogenic / likely-pathogenic (6)

Showing all 6 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
1527477	GRCh37/hg19 9p24.3-24.1(chr9:203861-7759331)x1	Pathogenic	criteria provided, single submitter	1
4819211	Single allele	Pathogenic	criteria provided, single submitter	1
3906943	CD274, IVS4DS, G-A, +1	Pathogenic	no assertion criteria provided	1
442671	GRCh37/hg19 9p24.3-23(chr9:203861-13486759)x1	Pathogenic	no assertion criteria provided	1
563686	GRCh37/hg19 9p24.3-q21.11(chr9:203861-70985795)x4	Pathogenic	no assertion criteria provided	1
1706515	GRCh37/hg19 9p24.3-23(chr9:203861-10283912)x1	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore CD274’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 39 predictions of 652):

Position(s)	Effect	Δscore	Sites
9:5450597–5450598	donor_loss	0.9900	5
9:5456166–5456167	donor_loss	0.9900	6
9:5457421–5457422	donor_loss	0.9900	5
9:5462826	acceptor_gain	0.9900
9:5462832–5462833	acceptor_loss	0.9900	6
9:5456093	acceptor_gain	0.9800
9:5456098–5456099	acceptor_loss	0.9800	6
9:5456168	donor_loss	0.9800	2
9:5457077–5457078	acceptor_loss	0.9800	6
9:5457422	donor_loss	0.9800

AlphaMissense

265 missense substitutions predicted likely pathogenic (of 1,923 scored), across 78 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
D108	8	0.956	0.983
D122	8	0.874	0.948
F19	8	0.829	0.959
C114	7	0.981	0.994
C155	7	0.971	0.987
W167	7	0.968	0.995
C40	7	0.967	0.991
C209	7	0.961	0.986
W57	7	0.936	0.991
F42	7	0.930	0.985
R84	7	0.871	0.974
F211	6	0.899	0.963
S195	6	0.888	0.978
G159	6	0.879	0.969
P161	6	0.868	0.927
G110	6	0.851	0.963
Y112	5	0.951	0.990
G95	5	0.908	0.973
F67	5	0.876	0.904
F207	5	0.874	0.915

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

1 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	0.000533

Disease associations

OMIM: gene MIM:605402 | disease phenotypes: MIM:621235

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
neonatal diabetes mellitus	Limited	Autosomal recessive

Mondo (3): autoimmune disease, multisystem, infantile-onset, 5 (MONDO:0979235), trisomy 9p (MONDO:0016526), neonatal diabetes mellitus (MONDO:0016391)

Orphanet (2): Trisomy 9p syndrome (Orphanet:236), Partial duplication/triplication of the short arm of chromosome 9 syndrome (Orphanet:262767)

HPO phenotypes

16 phenotypes (HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000750	Delayed speech and language development
HP:0000821	Hypothyroidism
HP:0001250	Seizure
HP:0001256	Mild intellectual disability
HP:0002099	Asthma
HP:0003593	Infantile onset
HP:0003623	Neonatal onset
HP:0011950	Unusual bronchiolitis
HP:0025329	Anti-glutamic acid decarboxylase antibody positivity
HP:0025373	Interictal EEG abnormality
HP:0025379	Anti-thyroid peroxidase antibody positivity
HP:0030795	Decreased circulating C-peptide concentration
HP:0034063	Anti-islet antigen-2 antibody positivity
HP:0034323	Reduced circulating growth hormone concentration
HP:0100651	Type I diabetes mellitus

GWAS associations

1 associations:

Study	Trait	p-value
GCST006585_289	Blood protein levels	2e-29

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (5): CHEMBL3580522 (SINGLE PROTEIN), CHEMBL4523993 (PROTEIN COMPLEX), CHEMBL5739543 (PROTEIN-PROTEIN INTERACTION), CHEMBL6066575 (PROTEIN FAMILY), CHEMBL6195520 (PROTEIN-PROTEIN INTERACTION)

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the CD274 protein itself — single-protein targets only (drugs acting on a protein family or complex that merely includes it are excluded). Includes antibodies and oligonucleotides that bioactivity screening does not capture.

13 curated-mechanism drugs:

Drug	Modality	Max phase
ATEZOLIZUMAB	Antibody	4
AVELUMAB	Antibody	4
COSIBELIMAB	Antibody	4
DURVALUMAB	Antibody	4
SUGEMALIMAB	Antibody	4
ADEBRELIMAB	Antibody	3
BINTRAFUSP ALFA	Protein	3
ENVAFOLIMAB	Antibody	3
ERFONRILIMAB	Antibody	3
SOCAZOLIMAB	Antibody	3
DANBURSTOTUG	Antibody	2
INCB-086550	Unknown	2
PACMILIMAB	Antibody	2

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 44,249 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

4 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL86304	MOCLOBEMIDE	4	13,612
CHEMBL1201303	PYRVINIUM	4	1,837
CHEMBL444633	RIFABUTIN	4	28,036
CHEMBL5095237	EVIXAPODLIN	1	764

Clinical evidence (CIViC)

Drug × variant × indication, from 15 curated evidence items; also 10 prognostic, 1 diagnostic. CIViC evidence level: A (validated) → B (clinical) → C (case study) → D (preclinical) → E (inferential).

12 predictive associations by evidence level:

Variant	Therapy	Indication	Effect	Level	CIViC
CD274 Expression	Atezolizumab	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC B	EID1172 +1
CD274 Expression	Pembrolizumab	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC B	EID1733 +1
CD274 Expression	Nivolumab + Pembrolizumab	Melanoma	Sensitivity/Response	CIViC B	EID704 +1
CD274 Expression	Atezolizumab + Avelumab + Nivolumab + Pembrolizumab	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC B	EID1167
CD274 Expression	Nivolumab	Cancer	Sensitivity/Response	CIViC B	EID1517
CD274 Expression	Pembrolizumab	Merkel Cell Carcinoma	Sensitivity/Response	CIViC B	EID1578
CD274 Expression	Nivolumab + Ipilimumab	Melanoma	Sensitivity/Response	CIViC B	EID1615
CD274 Expression	Durvalumab + Avelumab + Atezolizumab + Pembrolizumab + Nivolumab	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC B	EID4857
CD274 Expression	Pembrolizumab + Nivolumab	Lung Non-small Cell Carcinoma	Sensitivity/Response	CIViC B	EID743
CD274 Expression	Nivolumab	Nasopharynx Carcinoma	Sensitivity/Response	CIViC B	EID9010
CD274 Expression	Atezolizumab	Bladder Urothelial Carcinoma	Sensitivity/Response	CIViC B	EID9886
CD274 Expression	Radiation Therapy	Head And Neck Squamous Cell Carcinoma	Resistance	CIViC B	EID3000

CIViC column: a representative evidence item (EID); +N = additional CIViC items supporting the same association.

CIViC curated variants (1)

Named clinical variants curated in CIViC for this gene (the catalogue beneath the predictive evidence above):

Expression.

PharmGKB: 1 entry (CPIC guideline: no)

PharmGKB variant annotations

Per-publication pharmacogenomic findings for this gene (significant associations).

3 published findings:

Variant	Drug(s)	Category	Finding	PMID
rs2297136	carboplatin, cisplatin	Efficacy	Genotypes AG + GG is associated with increased likelihood of Progression-free survival when treated with carboplatin or cisplatin in people with Small cell carcinoma as compared to genotype AA.	PMID:40362483
rs822336	carboplatin, cisplatin	Efficacy	Genotypes CC + CG is associated with increased likelihood of Progression-free survival when treated with carboplatin or cisplatin in people with Small cell carcinoma as compared to genotype GG.	PMID:40362483
rs2282055	carboplatin, cisplatin	Efficacy	Genotypes GT + TT is associated with increased likelihood of Progression-free survival when treated with carboplatin or cisplatin in people with Small cell carcinoma as compared to genotype GG.	PMID:40362483

Binding affinities (BindingDB)

4393 measured of 6046 human assays (6100 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
CHEMBL4473436	KD	0.019 nM
N,N’-(2,2’-dimethyl-[1,1’- biphenyl]-3,3’-diyl)bis(5- ((((1-hydroxycyclopropyl) methyl)amino)methyl)-4- methoxypicolinamide)	IC50	0.032 nM	US-11459339: Biaryl derivative, preparation method thereof and pharmaceutical application thereof
3-[[6-[[3-[3-[[5-[[(3-carboxycyclobutyl)amino]methyl]-4-methoxypyridine-2-carbonyl]amino]-2-methylphenyl]-2-methylphenyl]carbamoyl]-4-methoxy-3-pyridinyl]methylamino]cyclobutane-1-carboxylic acid	IC50	0.034 nM	US-11459339: Biaryl derivative, preparation method thereof and pharmaceutical application thereof
CHEMBL5182195	IC50	0.04 nM
N,N’-(2,2’-dimethyl-[1,1’-biphenyl]- 3,3’-diyl)bis(5-(((2-hydroxyethyl) (methyl)amino)methyl)-4- methoxypicolinamide)	IC50	0.04 nM	US-11459339: Biaryl derivative, preparation method thereof and pharmaceutical application thereof
CHEMBL4865838	IC50	0.051 nM
CHEMBL4862360	IC50	0.058 nM
(5S)-5-[[[5-[2-chloro-3-[2-chloro-3-[5-[[[1-(2-hydroxyethyl)pyrazol-4-yl]methylamino]methyl]-6-methoxypyrazin-2-yl]phenyl]phenyl]-3-methoxypyrazin-2-yl]methylamino]methyl]pyrrolidin-2-one	IC50	0.06 nM	US-10710986: PD-1/PD-L1 inhibitors
1-[[5-[2-chloro-3-[2-chloro-3-[5-[(3-hydroxy-3-methylazetidin-1-yl)methyl]-6-methoxypyrazin-2-yl]phenyl]phenyl]-3-methoxypyrazin-2-yl]methyl]-3-methylazetidin-3-ol	IC50	0.06 nM	US-10710986: PD-1/PD-L1 inhibitors
[1-[[5-[2-chloro-3-[2-chloro-3-[5-[[3-(hydroxymethyl)-3-methylazetidin-1-yl]methyl]-6-methoxypyrazin-2-yl]phenyl]phenyl]-3-methoxypyrazin-2-yl]methyl]-3-methylazetidin-3-yl]methanol	IC50	0.06 nM	US-10710986: PD-1/PD-L1 inhibitors
(5S)-5-[[[5-[2-chloro-3-[2-chloro-3-[5-[[3-fluoro-3-(hydroxymethyl)azetidin-1-yl]methyl]-6-methoxypyrazin-2-yl]phenyl]phenyl]-3-methoxypyrazin-2-yl]methylamino]methyl]pyrrolidin-2-one	IC50	0.06 nM	US-10710986: PD-1/PD-L1 inhibitors
(5S)-5-[[[5-[2-chloro-3-[2-chloro-3-[5-[[(3-hydroxy-1,1-dioxothiolan-3-yl)methylamino]methyl]-6-methoxypyrazin-2-yl]phenyl]phenyl]-3-methoxypyrazin-2-yl]methylamino]methyl]pyrrolidin-2-one	IC50	0.06 nM	US-10710986: PD-1/PD-L1 inhibitors
(5S)-5-[[[5-[2-chloro-3-[2-chloro-3-[5-[(6-hydroxy-2-azaspiro[3.3]heptan-2-yl)methyl]-6-methoxypyrazin-2-yl]phenyl]phenyl]-3-methoxypyrazin-2-yl]methylamino]methyl]pyrrolidin-2-one	IC50	0.06 nM	US-10710986: PD-1/PD-L1 inhibitors
3-[[5-[2-chloro-3-[2-chloro-3-[6-methoxy-5-[[[(2S)-5-oxopyrrolidin-2-yl]methylamino]methyl]pyrazin-2-yl]phenyl]phenyl]-3-methoxypyrazin-2-yl]methylamino]propanamide	IC50	0.064 nM	US-10710986: PD-1/PD-L1 inhibitors
2-[[5-[2-chloro-3-[2-chloro-3-[6-(methylamino)-5-[(6-oxo-2,7-diazaspiro[3.4]octan-2-yl)methyl]pyrazin-2-yl]phenyl]phenyl]-3-(methylamino)pyrazin-2-yl]methyl]-2,7-diazaspiro[3.4]octan-6-one	IC50	0.064 nM	US-10710986: PD-1/PD-L1 inhibitors
2-[[5-[2-chloro-3-[2-chloro-3-[5-(4,5-dihydro-1H-imidazol-2-yl)-6-methoxy-2-pyridinyl]phenyl]phenyl]-3-methoxypyrazin-2-yl]methyl]-2,7-diazaspiro[3.4]octan-6-one	IC50	0.064 nM	US-10710986: PD-1/PD-L1 inhibitors
1-[[5-[2-chloro-3-[2-chloro-3-[5-(4,5-dihydro-1H-imidazol-2-yl)-6-methoxy-2-pyridinyl]phenyl]phenyl]-3-methoxypyrazin-2-yl]methyl]azetidin-3-ol	IC50	0.064 nM	US-10710986: PD-1/PD-L1 inhibitors
5-[2-chloro-3-[2-chloro-3-[6-methoxy-5-[(5S)-5-methyl-4,5-dihydro-1H-imidazol-2-yl]pyrazin-2-yl]phenyl]phenyl]-3-methoxy-2-[(5S)-5-methyl-4,5-dihydro-1H-imidazol-2-yl]pyrazine	IC50	0.064 nM	US-10710986: PD-1/PD-L1 inhibitors
5-[2-chloro-3-[2-chloro-3-[5-(5,5-dimethyl-1,4-dihydroimidazol-2-yl)-6-methoxypyrazin-2-yl]phenyl]phenyl]-2-(5,5-dimethyl-1,4-dihydroimidazol-2-yl)-3-methoxypyrazine	IC50	0.064 nM	US-10710986: PD-1/PD-L1 inhibitors
5-[2-chloro-3-[2-chloro-3-[6-methoxy-5-[(5R)-5-methyl-4,5-dihydro-1H-imidazol-2-yl]pyrazin-2-yl]phenyl]phenyl]-3-methoxy-2-[(5R)-5-methyl-4,5-dihydro-1H-imidazol-2-yl]pyrazine	IC50	0.064 nM	US-10710986: PD-1/PD-L1 inhibitors
[(5R)-2-[5-[2-chloro-3-[2-chloro-3-[5-[(5R)-5-(hydroxymethyl)-4,5-dihydro-1H-imidazol-2-yl]-6-methoxypyrazin-2-yl]phenyl]phenyl]-3-methoxypyrazin-2-yl]-4,5-dihydro-1H-imidazol-5-yl]methanol	IC50	0.064 nM	US-10710986: PD-1/PD-L1 inhibitors
[(5S)-2-[5-[2-chloro-3-[2-chloro-3-[5-[(5S)-5-(hydroxymethyl)-4,5-dihydro-1H-imidazol-2-yl]-6-methoxypyrazin-2-yl]phenyl]phenyl]-3-methoxypyrazin-2-yl]-4,5-dihydro-1H-imidazol-5-yl]methanol	IC50	0.064 nM	US-10710986: PD-1/PD-L1 inhibitors
5-[2-chloro-3-[2-chloro-3-[5-(4,5-dihydro-1H-imidazol-2-yl)-6-methoxypyrazin-2-yl]phenyl]phenyl]-2-(4,5-dihydro-1H-imidazol-2-yl)-3-methoxypyrazine	IC50	0.064 nM	US-10710986: PD-1/PD-L1 inhibitors
(5S)-5-[[[5-[2-chloro-3-[2-chloro-3-[5-[[3-(hydroxymethyl)azetidin-1-yl]methyl]-6-methoxy-2-pyridinyl]phenyl]phenyl]-3-methoxypyrazin-2-yl]methylamino]methyl]pyrrolidin-2-one	IC50	0.064 nM	US-10710986: PD-1/PD-L1 inhibitors
N-[4-[[5-[2-chloro-3-[2-chloro-3-[6-methoxy-5-[[[(2R)-5-oxopyrrolidin-2-yl]methylamino]methyl]pyrazin-2-yl]phenyl]phenyl]-3-methoxypyrazin-2-yl]methylamino]cyclohexyl]acetamide	IC50	0.064 nM	US-10710986: PD-1/PD-L1 inhibitors
(5S)-5-[[[5-[2-chloro-3-[2-chloro-3-[5-[[(3R,4R)-4-hydroxy-3-methylpiperidin-1-yl]methyl]-6-methoxypyrazin-2-yl]phenyl]phenyl]-3-methoxypyrazin-2-yl]methylamino]methyl]pyrrolidin-2-one	IC50	0.064 nM	US-10710986: PD-1/PD-L1 inhibitors
(5S)-5-[[[5-[2-chloro-3-[2-chloro-3-[6-methoxy-5-[[2-(oxolan-2-yl)ethylamino]methyl]pyrazin-2-yl]phenyl]phenyl]-3-methoxypyrazin-2-yl]methylamino]methyl]pyrrolidin-2-one	IC50	0.064 nM	US-10710986: PD-1/PD-L1 inhibitors
(5S)-5-[[[5-[2-chloro-3-[2-chloro-3-[5-[[(1-cyclopropyl-3-hydroxypropyl)amino]methyl]-6-methoxypyrazin-2-yl]phenyl]phenyl]-3-methoxypyrazin-2-yl]methylamino]methyl]pyrrolidin-2-one	IC50	0.064 nM	US-10710986: PD-1/PD-L1 inhibitors
(5S)-5-[[[5-[2-chloro-3-[2-chloro-3-[5-[[(3-hydroxycyclobutyl)methylamino]methyl]-6-methoxypyrazin-2-yl]phenyl]phenyl]-3-methoxypyrazin-2-yl]methylamino]methyl]pyrrolidin-2-one	IC50	0.064 nM	US-10710986: PD-1/PD-L1 inhibitors
(5S)-5-[[[5-[2-chloro-3-[2-chloro-3-[5-[[[(1R,3S)-3-hydroxycyclopentyl]amino]methyl]-6-methoxypyrazin-2-yl]phenyl]phenyl]-3-methoxypyrazin-2-yl]methylamino]methyl]pyrrolidin-2-one	IC50	0.064 nM	US-10710986: PD-1/PD-L1 inhibitors
(5S)-5-[[[5-[2-chloro-3-[2-chloro-3-[5-[(2,2-dioxo-2lambda6-thia-6-azaspiro[3.3]heptan-6-yl)methyl]-6-methoxypyrazin-2-yl]phenyl]phenyl]-3-methoxypyrazin-2-yl]methylamino]methyl]pyrrolidin-2-one	IC50	0.064 nM	US-10710986: PD-1/PD-L1 inhibitors
2-[[5-[2-chloro-3-[2-chloro-3-[6-methoxy-5-[[[(2S)-5-oxopyrrolidin-2-yl]methylamino]methyl]pyrazin-2-yl]phenyl]phenyl]-3-methoxypyrazin-2-yl]methyl]-2,7-diazaspiro[3.4]octan-6-one	IC50	0.064 nM	US-10710986: PD-1/PD-L1 inhibitors
1-[2-[[5-[2-chloro-3-[2-chloro-3-[6-methoxy-5-[[[(2S)-5-oxopyrrolidin-2-yl]methylamino]methyl]pyrazin-2-yl]phenyl]phenyl]-3-methoxypyrazin-2-yl]methylamino]ethyl]pyridin-2-one	IC50	0.064 nM	US-10710986: PD-1/PD-L1 inhibitors
(5S)-5-[2-[[5-[2-chloro-3-[2-chloro-3-[6-methoxy-5-[[2-[(2S)-5-oxopyrrolidin-2-yl]ethylamino]methyl]pyrazin-2-yl]phenyl]phenyl]-3-methoxypyrazin-2-yl]methylamino]ethyl]pyrrolidin-2-one	IC50	0.064 nM	US-10710986: PD-1/PD-L1 inhibitors
(5S)-5-[[[5-[2-chloro-3-[2-chloro-3-[6-methoxy-5-[[[(3R)-5-oxopyrrolidin-3-yl]methylamino]methyl]pyrazin-2-yl]phenyl]phenyl]-3-methoxypyrazin-2-yl]methylamino]methyl]pyrrolidin-2-one	IC50	0.064 nM	US-10710986: PD-1/PD-L1 inhibitors
(5S)-5-[[[5-[2-chloro-3-[2-chloro-3-[6-methoxy-5-[[3-(1H-pyrazol-4-yl)pyrrolidin-1-yl]methyl]pyrazin-2-yl]phenyl]phenyl]-3-methoxypyrazin-2-yl]methylamino]methyl]pyrrolidin-2-one	IC50	0.064 nM	US-10710986: PD-1/PD-L1 inhibitors
1-[6-[[5-[2-chloro-3-[2-chloro-3-[5-[(3-hydroxy-3-methylazetidin-1-yl)methyl]-6-methoxypyrazin-2-yl]phenyl]phenyl]-3-methoxypyrazin-2-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]ethanone	IC50	0.064 nM	US-10710986: PD-1/PD-L1 inhibitors
1-[[5-[2-chloro-3-[2-chloro-3-[5-[[(3R)-3-(hydroxymethyl)pyrrolidin-1-yl]methyl]-6-methoxypyrazin-2-yl]phenyl]phenyl]-3-methoxypyrazin-2-yl]methyl]-3-methylazetidin-3-ol	IC50	0.064 nM	US-10710986: PD-1/PD-L1 inhibitors
2-[[6-[2-chloro-3-[2-chloro-3-[6-methoxy-5-[(6-oxo-2,5-diazaspiro[3.4]octan-2-yl)methyl]pyrazin-2-yl]phenyl]phenyl]-1-methylpyrrolo[3,2-b]pyridin-3-yl]methyl]-2,5-diazaspiro[3.4]octan-6-one	IC50	0.064 nM	US-10710986: PD-1/PD-L1 inhibitors
2-[[5-[3-[3-[5-[(2-carbamoyloxyethylamino)methyl]-6-methoxypyrazin-2-yl]-2-chlorophenyl]-2-chlorophenyl]-3-methoxypyrazin-2-yl]methylamino]ethyl carbamate	IC50	0.064 nM	US-10710986: PD-1/PD-L1 inhibitors
2-[1-[[5-[2-chloro-3-[2-chloro-3-[5-[[3-(2-hydroxypropan-2-yl)azetidin-1-yl]methyl]-6-methoxypyrazin-2-yl]phenyl]phenyl]-3-methoxypyrazin-2-yl]methyl]azetidin-3-yl]propan-2-ol	IC50	0.064 nM	US-10710986: PD-1/PD-L1 inhibitors
(4R)-4-[[[5-[2-chloro-3-[2-chloro-3-[6-methoxy-5-[[[(3R)-5-oxopyrrolidin-3-yl]methylamino]methyl]pyrazin-2-yl]phenyl]phenyl]-3-methoxypyrazin-2-yl]methylamino]methyl]pyrrolidin-2-one	IC50	0.064 nM	US-10710986: PD-1/PD-L1 inhibitors
(5S)-5-[[[5-[3-[3-[5-[(2-acetyl-2,6-diazaspiro[3.3]heptan-6-yl)methyl]-6-(methylamino)pyrazin-2-yl]-2-chlorophenyl]-2-chlorophenyl]-3-methoxypyrazin-2-yl]methylamino]methyl]pyrrolidin-2-one	IC50	0.064 nM	US-10710986: PD-1/PD-L1 inhibitors
1-[6-[[6-[3-[3-[5-[(2-acetyl-2,6-diazaspiro[3.3]heptan-6-yl)methyl]-6-methoxypyrazin-2-yl]-2-chlorophenyl]-2-chlorophenyl]-1-methylpyrrolo[2,3-b]pyridin-3-yl]methyl]-2,6-diazaspiro[3.3]heptan-2-yl]ethanone	IC50	0.064 nM	US-10710986: PD-1/PD-L1 inhibitors
(5S)-5-[[[5-[2-chloro-3-[2-chloro-3-[5-[[(3S)-3-(2-hydroxypropan-2-yl)pyrrolidin-1-yl]methyl]-6-methoxypyrazin-2-yl]phenyl]phenyl]-3-methoxypyrazin-2-yl]methylamino]methyl]pyrrolidin-2-one	IC50	0.064 nM	US-10710986: PD-1/PD-L1 inhibitors
(3S)-1-[[5-[2-chloro-3-[2-chloro-3-[6-methoxy-5-[[[(2S)-5-oxopyrrolidin-2-yl]methylamino]methyl]-2-pyridinyl]phenyl]phenyl]-3-methoxypyrazin-2-yl]methyl]pyrrolidine-3-carboxylic acid	IC50	0.064 nM	US-10710986: PD-1/PD-L1 inhibitors
(5S)-5-[[[5-[2-chloro-3-[2-chloro-3-[5-[[(2S,3S)-3-hydroxy-2-methylpyrrolidin-1-yl]methyl]-6-methoxypyrazin-2-yl]phenyl]phenyl]-3-methoxypyrazin-2-yl]methylamino]methyl]pyrrolidin-2-one	IC50	0.064 nM	US-10710986: PD-1/PD-L1 inhibitors
(5S)-5-[[[5-[3-[3-[5-[[bis(2-hydroxyethyl)amino]methyl]-6-methoxypyrazin-2-yl]-2-chlorophenyl]-2-chlorophenyl]-3-methoxypyrazin-2-yl]methylamino]methyl]pyrrolidin-2-one	IC50	0.064 nM	US-10710986: PD-1/PD-L1 inhibitors
1-[1-[[5-[2-chloro-3-[2-chloro-3-[6-methoxy-5-[[[(2S)-5-oxopyrrolidin-2-yl]methylamino]methyl]pyrazin-2-yl]phenyl]phenyl]-3-methoxypyrazin-2-yl]methyl]pyrrolidin-3-yl]imidazolidin-2-one	IC50	0.064 nM	US-10710986: PD-1/PD-L1 inhibitors
7-[[5-[2-chloro-3-[2-chloro-3-[6-methoxy-5-[(2-oxo-1,7-diazaspiro[4.4]nonan-7-yl)methyl]pyrazin-2-yl]phenyl]phenyl]-3-methoxypyrazin-2-yl]methyl]-1,7-diazaspiro[4.4]nonan-2-one	IC50	0.064 nM	US-10710986: PD-1/PD-L1 inhibitors

ChEMBL bioactivities

5925 potent at pChembl≥5 of 6100 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
11.00	IC50	0.01	nM	CHEMBL5411833
10.72	Kd	0.019	nM	CHEMBL4473436
10.49	IC50	0.032	nM	CHEMBL6041367
10.47	IC50	0.034	nM	CHEMBL5816891
10.40	IC50	0.04	nM	CHEMBL5182195
10.40	IC50	0.04	nM	CHEMBL6061706
10.29	IC50	0.051	nM	CHEMBL4865838
10.24	IC50	0.058	nM	CHEMBL4862360
10.22	IC50	0.06	nM	CHEMBL5890938
10.22	IC50	0.06	nM	CHEMBL5777528
10.22	IC50	0.06	nM	CHEMBL5889053
10.22	IC50	0.06	nM	CHEMBL5743690
10.22	IC50	0.06	nM	CHEMBL5920904
10.22	IC50	0.06	nM	CHEMBL5831012
10.19	IC50	0.064	nM	CHEMBL6025911
10.19	IC50	0.064	nM	CHEMBL5944322
10.19	IC50	0.064	nM	CHEMBL5975129
10.19	IC50	0.064	nM	CHEMBL5971416
10.19	IC50	0.064	nM	CHEMBL5926015
10.19	IC50	0.064	nM	CHEMBL5917876
10.19	IC50	0.064	nM	CHEMBL5970033
10.19	IC50	0.064	nM	CHEMBL5755581
10.19	IC50	0.064	nM	CHEMBL5965337
10.19	IC50	0.064	nM	CHEMBL6020002
10.19	IC50	0.064	nM	CHEMBL5773471
10.19	IC50	0.064	nM	CHEMBL6053156
10.19	IC50	0.064	nM	CHEMBL5791950
10.19	IC50	0.064	nM	CHEMBL5833807
10.19	IC50	0.064	nM	CHEMBL5826045
10.19	IC50	0.064	nM	CHEMBL5785770
10.19	IC50	0.064	nM	CHEMBL5964067
10.19	IC50	0.064	nM	CHEMBL6006236
10.19	IC50	0.064	nM	CHEMBL5785148
10.19	IC50	0.064	nM	CHEMBL5826709
10.19	IC50	0.064	nM	CHEMBL5758891
10.19	IC50	0.064	nM	CHEMBL5948806
10.19	IC50	0.064	nM	CHEMBL5856770
10.19	IC50	0.064	nM	CHEMBL5989882
10.19	IC50	0.064	nM	CHEMBL5827762
10.19	IC50	0.064	nM	CHEMBL6037230
10.19	IC50	0.064	nM	CHEMBL5966006
10.19	IC50	0.064	nM	CHEMBL5864311
10.19	IC50	0.064	nM	CHEMBL5894438
10.19	IC50	0.064	nM	CHEMBL5971082
10.19	IC50	0.064	nM	CHEMBL5772234
10.19	IC50	0.064	nM	CHEMBL5847490
10.19	IC50	0.064	nM	CHEMBL6008168
10.19	IC50	0.064	nM	CHEMBL5891751
10.19	IC50	0.064	nM	CHEMBL5765331
10.19	IC50	0.064	nM	CHEMBL5915120

PubChem BioAssay actives

1598 with measured affinity, of 3144 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(2S)-1-[[4-[[2-bromo-3-(2,3-dihydro-1,4-benzodioxin-6-yl)phenyl]methoxy]-5-chloro-2-[(2-cyano-4-pyridinyl)methoxy]phenyl]methyl]piperidine-2-carboxylic acid	1985059: Inhibition of His-tagged PD-1 (unknown origin)/hFc-tagged PD-L1 (unknown origin) protein-protein interaction incubated for 15 mins by HTRF assay	ic50	<0.0001	uM
(2S)-1-[[4-[(2-bromo-3-phenylphenyl)methoxy]-5-chloro-2-[(2-cyano-4-pyridinyl)methoxy]phenyl]methyl]piperidine-2-carboxylic acid	1985059: Inhibition of His-tagged PD-1 (unknown origin)/hFc-tagged PD-L1 (unknown origin) protein-protein interaction incubated for 15 mins by HTRF assay	ic50	<0.0001	uM
(2S)-1-[[4-[(2-bromo-3-phenylphenyl)methoxy]-5-chloro-2-[(5-cyano-3-pyridinyl)methoxy]phenyl]methyl]piperidine-2-carboxylic acid	1985059: Inhibition of His-tagged PD-1 (unknown origin)/hFc-tagged PD-L1 (unknown origin) protein-protein interaction incubated for 15 mins by HTRF assay	ic50	<0.0001	uM
(2R)-2-[[4-[[3-[3-[[4-[[[(1R)-1-carboxy-2-hydroxyethyl]amino]methyl]-3-[(5-cyano-3-pyridinyl)methoxy]phenoxy]methyl]-2-methylphenyl]-2-methylphenyl]methoxy]-2-[(5-cyano-3-pyridinyl)methoxy]phenyl]methylamino]-3-hydroxypropanoic acid	1634345: Binding affinity to FC-tagged human PDL1 by SPR assay	kd	<0.0001	uM
(2S)-1-[[4-[2-(2-bromo-3-phenylphenyl)ethyl]-5-chloro-2-[(2-cyano-4-pyridinyl)methoxy]phenyl]methyl]piperidine-2-carboxylic acid	1533369: Inhibition of recombinant human PD1 (25 to 167 residues)/human PDL1 (19 to 238 residues) interaction after 40 mins by HTRF assay	ic50	<0.0001	uM
(2S)-2-[[4-[[3-[3-[[4-[[[(1R)-1-carboxy-3-hydroxypropyl]amino]methyl]-2-chloro-5-[(3-cyanophenyl)methoxy]phenoxy]methyl]-2-methylphenyl]phenyl]methoxy]-5-chloro-2-(pyridin-3-ylmethoxy)phenyl]methylamino]-4-hydroxybutanoic acid	1845762: Inhibition of PD-1/PD-L1 interaction (unknown origin) by HTRF binding assay	ic50	<0.0001	uM
(2S)-1-[[4-[2-(2-bromo-3-phenylphenyl)ethyl]-2-[(2-cyano-4-pyridinyl)methoxy]phenyl]methyl]piperidine-2-carboxylic acid	1845764: Inhibition of His-tagged PD-1/PD-L1 interaction (unknown origin) incubated for 1 to 4 hrs by HTRF binding assay	ic50	<0.0001	uM
(2S,4S)-1-[[6-[[(1S)-4-[(1S)-1-[[5-[[(2S,4S)-2-carboxy-4-hydroxypyrrolidin-1-yl]methyl]-3-chloro-6-[(5-methylsulfonyl-3-pyridinyl)methoxy]-2-pyridinyl]oxy]-2,3-dihydro-1H-inden-4-yl]-2,3-dihydro-1H-inden-1-yl]oxy]-5-chloro-2-[(5-methylsulfonyl-3-pyridinyl)methoxy]-3-pyridinyl]methyl]-4-hydroxypyrrolidine-2-carboxylic acid	1752584: Inhibition of PD1/PD-L1 (unknown origin)	ic50	0.0001	uM
(2S)-2-[[6-[[(1S)-4-[(1S)-1-[[5-[[[(2S)-2-carboxy-1-hydroxypropan-2-yl]amino]methyl]-3-chloro-6-[(5-methylsulfonyl-3-pyridinyl)methoxy]-2-pyridinyl]oxy]-2,3-dihydro-1H-inden-4-yl]-2,3-dihydro-1H-inden-1-yl]oxy]-5-chloro-2-[(5-methylsulfonyl-3-pyridinyl)methoxy]-3-pyridinyl]methylamino]-3-hydroxy-2-methylpropanoic acid	1752584: Inhibition of PD1/PD-L1 (unknown origin)	ic50	0.0001	uM
(2R)-1-[[6-[[3-[3-[(2R)-2-amino-2,3-dihydro-1H-inden-5-yl]-2-chlorophenyl]-2-chlorophenyl]methoxy]-5-bromo-2-[2-(5-methylsulfonyl-3-pyridinyl)ethyl]-3-pyridinyl]methyl]piperidine-2-carboxylic acid	2035804: Inhibition of human PD-L1/PD-L1 interaction incubated for 15 mins by TR-FRET assay	ic50	0.0001	uM
(2S)-1-[[5-chloro-2-[(3-cyanophenyl)methoxy]-4-[[2-methyl-3-[2-methyl-3-(3-morpholin-4-ylpropoxy)phenyl]phenyl]methoxy]phenyl]methyl]piperidine-2-carboxylic acid	2035797: Inhibition of PD-L1 (unknown origin) by HTRF assay	ic50	0.0002	uM
(5S)-5-[[[5-[2-chloro-3-[2-chloro-3-[6-methoxy-5-[[[(2S)-5-oxopyrrolidin-2-yl]methylamino]methyl]pyrazin-2-yl]phenyl]phenyl]-3-methoxypyrazin-2-yl]methylamino]methyl]pyrrolidin-2-one	2089806: Inhibition of PD-1/PD-L1 interaction (unknown origin)	ic50	0.0002	uM
(2R)-2-[[4-[[3-[3-[[4-[[[(1R)-1-carboxy-2-hydroxyethyl]amino]methyl]-3-[(5-cyano-3-pyridinyl)methoxy]phenoxy]methyl]-2-methylphenyl]phenyl]methoxy]-2-[(5-cyano-3-pyridinyl)methoxy]phenyl]methylamino]-3-hydroxypropanoic acid	1634345: Binding affinity to FC-tagged human PDL1 by SPR assay	kd	0.0002	uM
(2R)-2-[[4-[[3-[3-[[4-[[[(1R)-1-carboxy-2-hydroxyethyl]amino]methyl]-3-[(5-cyano-3-pyridinyl)methoxy]phenoxy]methyl]-2-methylphenyl]-2-methylphenyl]methoxy]-2-methoxyphenyl]methylamino]-3-hydroxypropanoic acid	1634345: Binding affinity to FC-tagged human PDL1 by SPR assay	kd	0.0002	uM
(5S)-5-[[[6-[2-chloro-3-[1-[4-[(3-hydroxy-3-methylazetidin-1-yl)methyl]-3,5-dimethoxyphenyl]indazol-4-yl]phenyl]-2-methoxy-3-pyridinyl]methylamino]methyl]pyrrolidin-2-one	2128947: Inhibition of Fc-tagged recombinant human PD-1/His-tagged recombinant human PD-L1 interaction by ALPHA assay	ic50	0.0002	uM
(5S)-5-[[[6-[2-chloro-3-[1-[3,5-dimethoxy-4-[[[(2S)-5-oxopyrrolidin-2-yl]methylamino]methyl]phenyl]indol-4-yl]phenyl]-2-methoxy-3-pyridinyl]methylamino]methyl]pyrrolidin-2-one	2128947: Inhibition of Fc-tagged recombinant human PD-1/His-tagged recombinant human PD-L1 interaction by ALPHA assay	ic50	0.0002	uM
ethyl (E)-2-cyano-3-(3-cyanophenyl)prop-2-enoate	1985066: Inhibition of [89Zr]Zr-atezolizumab binding from human PD-L1 transfected in CHO cells preincubated for 30 mins followed by [89Zr]Zr-atezolizumab addition measured after 60 mins by Wizard2 gamma counter analysis	ki	0.0002	uM
2-[3-[[(3S,6S,9S,15S,18S,21S,27R,30S,33S,36S,39S,42S,45S,48S,50R)-42-(2-aminoethyl)-6-(aminomethyl)-15-(2-amino-2-oxoethyl)-27-[(2-amino-2-oxoethyl)carbamoyl]-33,36-dibutyl-50-hydroxy-21-[(4-hydroxyphenyl)methyl]-45-(1H-indol-3-ylmethyl)-18,19,34,37-tetramethyl-3,30-bis(2-methylpropyl)-2,5,8,14,17,20,23,29,32,35,38,41,44,47-tetradecaoxo-25-thia-1,4,7,13,16,19,22,28,31,34,37,40,43,46-tetradecazatricyclo[46.3.0.09,13]henpentacontan-39-yl]methyl]indol-1-yl]acetic acid	2099894: Inhibition of PD-1/PD-L1 (unknown origin) protein-protein interaction expressed in HEK293 cells by HTRF method	ic50	0.0003	uM
(2R)-2-[[4-[[3-[3-[[4-[[[(1R)-1-carboxy-2-hydroxyethyl]amino]methyl]-3-[(5-cyano-3-pyridinyl)methoxy]phenoxy]methyl]-2-methylphenyl]-2-methylphenyl]methoxy]phenyl]methylamino]-3-hydroxypropanoic acid	1634345: Binding affinity to FC-tagged human PDL1 by SPR assay	kd	0.0003	uM
2-[[6-[2-chloro-3-[1-[3,5-dimethoxy-4-[[[(2S)-5-oxopyrrolidin-2-yl]methylamino]methyl]phenyl]indazol-4-yl]phenyl]-2-methoxy-3-pyridinyl]methyl]-2,5-diazaspiro[3.4]octan-6-one	2128947: Inhibition of Fc-tagged recombinant human PD-1/His-tagged recombinant human PD-L1 interaction by ALPHA assay	ic50	0.0003	uM
2-[[6-[2-chloro-3-[1-[3,5-dimethoxy-4-[[[(2S)-5-oxopyrrolidin-2-yl]methylamino]methyl]phenyl]indazol-4-yl]phenyl]-2-methoxy-3-pyridinyl]methyl]-2,7-diazaspiro[3.4]octan-6-one	2128947: Inhibition of Fc-tagged recombinant human PD-1/His-tagged recombinant human PD-L1 interaction by ALPHA assay	ic50	0.0003	uM
2-[(3R,6S,9S,12S,15S,18S,21S,24S,27S,30S,33S,36S)-3-[(2-amino-2-oxoethyl)carbamoyl]-9,36-dibenzyl-24,30-bis[(2S)-butan-2-yl]-6,15,21-tris[3-(diaminomethylideneamino)propyl]-33-(2-methylpropyl)-5,8,11,14,17,20,23,26,29,32,35,38-dodecaoxo-12,27-di(propan-2-yl)-1-thia-4,7,10,13,16,19,22,25,28,31,34,37-dodecazacyclononatriacont-18-yl]acetic acid	1930232: Inhibition of human PD-1 expressed in rat PBMCs/human PD-L1 expressed in MDA-MB-231 cells protein-protein interaction assessed as increase in PBMCs proliferation	ec50	0.0004	uM
5-[(2-hydroxyethylamino)methyl]-N-[3-[3-[[5-[(2-hydroxyethylamino)methyl]pyridine-2-carbonyl]amino]-2-methylphenyl]-2-methylphenyl]pyridine-2-carboxamide	1998919: Inhibition of PD-1 (unknown origin)/PD-L1 (unknown origin) interaction by HTRF binding assay	ic50	0.0004	uM
2-[[4-[4-[2-chloro-3-[5-[[(3-hydroxycyclobutyl)amino]methyl]-6-methoxy-2-pyridinyl]phenyl]indazol-1-yl]-2,6-dimethoxyphenyl]methyl]-2,7-diazaspiro[3.4]octan-6-one	2128947: Inhibition of Fc-tagged recombinant human PD-1/His-tagged recombinant human PD-L1 interaction by ALPHA assay	ic50	0.0004	uM
(5S)-5-[[[6-[2-chloro-3-[1-[4-[[(3-hydroxycyclobutyl)methylamino]methyl]-3,5-dimethoxyphenyl]indazol-4-yl]phenyl]-2-methoxy-3-pyridinyl]methylamino]methyl]pyrrolidin-2-one	2128947: Inhibition of Fc-tagged recombinant human PD-1/His-tagged recombinant human PD-L1 interaction by ALPHA assay	ic50	0.0004	uM
(5S)-5-[[[4-[4-[3-[5-[(2-acetyl-2,6-diazaspiro[3.3]heptan-6-yl)methyl]-6-methoxy-2-pyridinyl]-2-chlorophenyl]indazol-1-yl]-2,6-dimethoxyphenyl]methylamino]methyl]pyrrolidin-2-one	2128947: Inhibition of Fc-tagged recombinant human PD-1/His-tagged recombinant human PD-L1 interaction by ALPHA assay	ic50	0.0004	uM
5-[[4-chloro-5-[[3-[3-[3-(3,3-difluoropyrrolidin-1-yl)propoxy]-2-methylphenyl]-2-methylphenyl]methoxy]-2-[[[1,3-dihydroxy-2-(hydroxymethyl)propan-2-yl]-methylamino]methyl]phenoxy]methyl]pyridine-3-carbonitrile	1652976: Inhibition of human PD1/PDL1 protein-protein interaction by HTRF assay	ic50	0.0005	uM
(2S)-1-[[5-chloro-2-[(5-cyano-3-pyridinyl)methoxy]-4-[[3-[3-[3-(4-hydroxypiperidin-1-yl)propoxy]-2-methylphenyl]-2-methylphenyl]methoxy]phenyl]methyl]piperidine-2-carboxylic acid	2035797: Inhibition of PD-L1 (unknown origin) by HTRF assay	ic50	0.0005	uM
(2S)-2-[[5-chloro-2-[(5-cyano-3-pyridinyl)methoxy]-4-[[3-[3-[3-(4-hydroxypiperidin-1-yl)propoxy]phenyl]-2-methylphenyl]methoxy]phenyl]methylamino]-3-hydroxypropanoic acid	1845762: Inhibition of PD-1/PD-L1 interaction (unknown origin) by HTRF binding assay	ic50	0.0005	uM
1-[[4-[2-chloro-3-(2,3-dihydro-1,4-benzodioxin-6-yl)phenyl]-2-methoxyphenyl]methyl]-N’,N’-dimethylpiperidine-4-carbohydrazide	1978454: Inhibition of human PD-1/PDL1 interaction incubated for 1 hr by HTRF assay	ic50	0.0005	uM
1-[[4-[2-chloro-3-(2,3-dihydro-1,4-benzodioxin-6-yl)phenyl]-2-methoxyphenyl]methyl]pyrrolidine-2-carboxylic acid	1978454: Inhibition of human PD-1/PDL1 interaction incubated for 1 hr by HTRF assay	ic50	0.0005	uM
1-[[4-[2-chloro-3-(2,3-dihydro-1,4-benzodioxin-6-yl)phenyl]-2-methoxyphenyl]methyl]-N-(1,3-dihydroxypropan-2-yl)pyrrolidine-3-carboxamide	1978454: Inhibition of human PD-1/PDL1 interaction incubated for 1 hr by HTRF assay	ic50	0.0005	uM
1-[[4-[2-chloro-3-(2,3-dihydro-1,4-benzodioxin-6-yl)phenyl]-2-methoxyphenyl]methyl]-N-(2-hydroxyethyl)pyrrolidine-3-carboxamide	1978454: Inhibition of human PD-1/PDL1 interaction incubated for 1 hr by HTRF assay	ic50	0.0005	uM
N-(2-aminoethyl)-1-[[4-[2-chloro-3-(2,3-dihydro-1,4-benzodioxin-6-yl)phenyl]-2-methoxyphenyl]methyl]piperidine-4-carboxamide	1978454: Inhibition of human PD-1/PDL1 interaction incubated for 1 hr by HTRF assay	ic50	0.0005	uM
1-[[4-[2-chloro-3-(2,3-dihydro-1,4-benzodioxin-6-yl)phenyl]-2-methoxyphenyl]methyl]-N’,N’-dimethylpyrrolidine-2-carbohydrazide	1978454: Inhibition of human PD-1/PDL1 interaction incubated for 1 hr by HTRF assay	ic50	0.0005	uM
1-[[4-[2-chloro-3-(2,3-dihydro-1,4-benzodioxin-6-yl)phenyl]-2-methoxyphenyl]methyl]piperidine-3-carboxylic acid	1978454: Inhibition of human PD-1/PDL1 interaction incubated for 1 hr by HTRF assay	ic50	0.0005	uM
1-[[4-[2-chloro-3-(2,3-dihydro-1,4-benzodioxin-6-yl)phenyl]-2-methoxyphenyl]methyl]-N-(1,3-dihydroxypropan-2-yl)piperidine-4-carboxamide	1978454: Inhibition of human PD-1/PDL1 interaction incubated for 1 hr by HTRF assay	ic50	0.0005	uM
1-[[4-[2-chloro-3-(2,3-dihydro-1,4-benzodioxin-6-yl)phenyl]-2-methoxyphenyl]methyl]-N-(1,3-dihydroxypropan-2-yl)pyrrolidine-2-carboxamide	1978454: Inhibition of human PD-1/PDL1 interaction incubated for 1 hr by HTRF assay	ic50	0.0005	uM
1-[[4-[2-chloro-3-(2,3-dihydro-1,4-benzodioxin-6-yl)phenyl]-2-methoxyphenyl]methyl]-N-(2-hydroxyethyl)pyrrolidine-2-carboxamide	1978454: Inhibition of human PD-1/PDL1 interaction incubated for 1 hr by HTRF assay	ic50	0.0005	uM
N-(2-aminoethyl)-1-[[4-[2-chloro-3-(2,3-dihydro-1,4-benzodioxin-6-yl)phenyl]-2-methoxyphenyl]methyl]pyrrolidine-2-carboxamide	1978454: Inhibition of human PD-1/PDL1 interaction incubated for 1 hr by HTRF assay	ic50	0.0005	uM
1-[[4-[2-chloro-3-(2,3-dihydro-1,4-benzodioxin-6-yl)phenyl]-2-methoxyphenyl]methyl]-N-[1,3-dihydroxy-2-(hydroxymethyl)propan-2-yl]pyrrolidine-2-carboxamide	1978454: Inhibition of human PD-1/PDL1 interaction incubated for 1 hr by HTRF assay	ic50	0.0005	uM
1-[[4-[2-chloro-3-(2,3-dihydro-1,4-benzodioxin-6-yl)phenyl]-2-methoxyphenyl]methyl]-N-[1,3-dihydroxy-2-(hydroxymethyl)propan-2-yl]pyrrolidine-3-carboxamide	1978454: Inhibition of human PD-1/PDL1 interaction incubated for 1 hr by HTRF assay	ic50	0.0005	uM
1-[[4-[2-chloro-3-(2,3-dihydro-1,4-benzodioxin-6-yl)phenyl]-2-methoxyphenyl]methyl]-N-[1,3-dihydroxy-2-(hydroxymethyl)propan-2-yl]piperidine-4-carboxamide	1978454: Inhibition of human PD-1/PDL1 interaction incubated for 1 hr by HTRF assay	ic50	0.0005	uM
1-[[4-[2-chloro-3-(2,3-dihydro-1,4-benzodioxin-6-yl)phenyl]-2-methoxyphenyl]methyl]pyrrolidine-3-carbohydrazide	1978454: Inhibition of human PD-1/PDL1 interaction incubated for 1 hr by HTRF assay	ic50	0.0005	uM
1-[[4-[2-chloro-3-(2,3-dihydro-1,4-benzodioxin-6-yl)phenyl]-2-methoxyphenyl]methyl]-N-(2-hydroxyethyl)piperidine-3-carboxamide	1978454: Inhibition of human PD-1/PDL1 interaction incubated for 1 hr by HTRF assay	ic50	0.0005	uM
1-[[4-[2-chloro-3-(2,3-dihydro-1,4-benzodioxin-6-yl)phenyl]-2-methoxyphenyl]methyl]piperidine-4-carboxylic acid	1978454: Inhibition of human PD-1/PDL1 interaction incubated for 1 hr by HTRF assay	ic50	0.0005	uM
1-[[4-[2-chloro-3-(2,3-dihydro-1,4-benzodioxin-6-yl)phenyl]-2-methoxyphenyl]methyl]-N-(2-hydroxyethyl)piperidine-4-carboxamide	1978454: Inhibition of human PD-1/PDL1 interaction incubated for 1 hr by HTRF assay	ic50	0.0006	uM
1-[[4-[2-chloro-3-(2,3-dihydro-1,4-benzodioxin-6-yl)phenyl]-2-methoxyphenyl]methyl]piperidine-2-carboxylic acid	1978454: Inhibition of human PD-1/PDL1 interaction incubated for 1 hr by HTRF assay	ic50	0.0006	uM
5-(3,4-dimethoxyphenyl)-2-pyridin-2-yl-4H-pyrazol-3-one	1908515: Binding affinity towards His-tagged recombinant human PD-L1 measured by MST dimerization binding assay	kd	0.0007	uM
(5S)-5-[[[6-[2-chloro-3-[1-[3,5-dimethoxy-4-[[[(2S)-5-oxopyrrolidin-2-yl]methylamino]methyl]phenyl]indazol-4-yl]phenyl]-2-methoxy-3-pyridinyl]methylamino]methyl]pyrrolidin-2-one	2128947: Inhibition of Fc-tagged recombinant human PD-1/His-tagged recombinant human PD-L1 interaction by ALPHA assay	ic50	0.0007	uM

CTD chemical–gene interactions

125 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, decreases methylation	4
Lipopolysaccharides	increases reaction, affects response to substance, affects cotreatment, increases expression	3
Nickel	increases expression	3
immune checkpoint inhibitor BMS-1	affects binding, affects cotreatment, decreases expression, increases reaction	2
cinnamaldehyde	increases expression	2
sodium arsenite	affects binding, increases reaction, decreases expression, increases expression	2
nickel sulfate	decreases expression, increases expression	2
evodiamine	decreases reaction, increases expression, decreases expression	2
CPG-oligonucleotide	increases expression, increases reaction, decreases reaction	2
Benzo(a)pyrene	increases expression	2
Calcitriol	increases expression, affects cotreatment	2
Cisplatin	decreases expression, increases reaction	2
Dinitrochlorobenzene	increases expression	2
Manganese	decreases expression, increases abundance, increases expression	2
Carboplatin	decreases expression	2
Lactic Acid	decreases reaction, increases expression, affects reaction	2
Particulate Matter	increases abundance, increases expression	2
Paris saponin VII	affects cotreatment, decreases expression, decreases phosphorylation	1
Glupearl 19S	increases expression	1
GW 506033X	increases expression	1
nano-diamino-tetrac	decreases expression, increases reaction, decreases reaction, increases expression	1
abivertinib	affects binding	1
sotorasib	affects cotreatment, decreases expression	1
disitamab vedotin	affects reaction, increases response to substance	1
TL8-506	affects cotreatment, increases expression	1
spinacetin	affects binding	1
kaempferol	affects binding	1
bisphenol A	decreases expression	1
kojic acid	increases expression	1
trichostatin A	increases expression	1

ChEMBL screening assays

525 unique, capped per target: 520 binding, 5 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3583018	Binding	Binding affinity to His-tagged PD-L1 (unknown origin) assessed as inhibition of interaction with PD1 preincubated for 15 mins followed by PD1 addition measured after 15 mins by HTRF assay	Inhibitors of the PD-1/PD-L1 Pathway Can Mobilize the Immune System: An Innovative Potential Therapy for Cancer and Chronic Infections. — *ACS Med Chem Lett*
CHEMBL4769870	Functional	Protac like activity at CRBN/PD-L1 in human MDA-MB-231 cells assessed as reduction in cell surface PD-L1 expression at 10 uM measured after 24 hrs by flow cytometry relative to control	Discovery of novel resorcinol diphenyl ether-based PROTAC-like molecules as dual inhibitors and degraders of PD-L1. — *Eur J Med Chem*

Cellosaurus cell lines

37 cell lines: 25 cancer cell line, 6 transformed cell line, 5 spontaneously immortalized cell line, 1 induced pluripotent stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A8AE	Raji-hPD-L1	Cancer cell line	Male
CVCL_B1ER	Abcam A-549 CD274 KO 1	Cancer cell line	Male
CVCL_B2MA	Abcam A-549 CD274 KO 2	Cancer cell line	Male
CVCL_B7NL	MC38-hPD-L1	Cancer cell line	Female
CVCL_B7NP	CT26-hPD-L1	Cancer cell line	Female
CVCL_B7Q0	MC38-hPD-L1-LZ	Cancer cell line	Female
CVCL_C9D8	KSCBi005-A-8	Induced pluripotent stem cell	Male
CVCL_D2S5	LN229/hPD-L1	Cancer cell line	Female
CVCL_D2S6	CHO/hPD-L1	Spontaneously immortalized cell line	Female
CVCL_D6CP	HyCyte THP-1 KO-hCD274	Cancer cell line	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for CD274 across ~30M SureChEMBL compounds — explore on Sugi Predict.