EGLN1

Summary

EGLN1 (egl-9 family hypoxia inducible factor 1, HGNC:1232) is a protein-coding gene on chromosome 1q42.2, encoding Egl nine homolog 1 (Q9GZT9). Cellular oxygen sensor that catalyzes, under normoxic conditions, the post-translational formation of 4-hydroxyproline in hypoxia-inducible factor (HIF) alpha proteins. It is a selective cancer dependency (DepMap: 16.6% of cell lines).

The protein encoded by this gene catalyzes the post-translational formation of 4-hydroxyproline in hypoxia-inducible factor (HIF) alpha proteins. HIF is a transcriptional complex that plays a central role in mammalian oxygen homeostasis. This protein functions as a cellular oxygen sensor, and under normal oxygen concentration, modification by prolyl hydroxylation is a key regulatory event that targets HIF subunits for proteasomal destruction via the von Hippel-Lindau ubiquitylation complex. Mutations in this gene are associated with erythrocytosis familial type 3 (ECYT3).

Source: NCBI Gene 54583 — RefSeq curated summary.

At a glance

• Gene–disease (curated): EGLN1-related erythrocytosis and pheochromocytoma/paraganglioma predisposition (Definitive, ClinGen) — +4 more curated relationships
• GWAS associations: 15
• Clinical variants (ClinVar): 1,294 total — 12 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 5
• Druggable target: yes — 11 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 16.6% of screened cell lines
• MANE Select transcript: NM_022051

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1232
Approved symbol	EGLN1
Name	egl-9 family hypoxia inducible factor 1
Location	1q42.2
Locus type	gene with protein product
Status	Approved
Aliases	SM-20, PHD2, ZMYND6, HIFPH2
Ensembl gene	ENSG00000135766
Ensembl biotype	protein_coding
OMIM	606425
Entrez	54583

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 7 protein_coding, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000366641, ENST00000476717, ENST00000654803, ENST00000658954, ENST00000663780, ENST00000667629, ENST00000670301, ENST00000889866, ENST00000889867, ENST00000951830

RefSeq mRNA: 3 — MANE Select: NM_022051 NM_001377260, NM_001377261, NM_022051

CCDS: CCDS1595

Canonical transcript exons

ENST00000366641 — 5 exons

Exon	Start	End
ENSE00001257532	231420998	231422287
ENSE00003466537	231370562	231370698
ENSE00003555551	231373980	231374099
ENSE00003587948	231367569	231367636
ENSE00003861393	231363756	231366475

Expression profiles

Bgee: expression breadth ubiquitous, 214 present calls, max score 98.83.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 25.4190 / max 551.4716, expressed in 1811 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
17986	23.5286	1807
17991	0.4827	259
17987	0.4664	263
17988	0.3417	171
17983	0.1632	31
17989	0.1568	63
17982	0.1260	47
17984	0.1129	31
17985	0.0219	4
17990	0.0188	4

Top tissues by expression

244 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
gastrocnemius	UBERON:0001388	98.83	gold quality
muscle of leg	UBERON:0001383	98.61	gold quality
adrenal tissue	UBERON:0018303	97.93	gold quality
calcaneal tendon	UBERON:0003701	97.91	gold quality
hindlimb stylopod muscle	UBERON:0004252	97.73	gold quality
cortical plate	UBERON:0005343	96.50	gold quality
ventricular zone	UBERON:0003053	95.85	gold quality
islet of Langerhans	UBERON:0000006	95.56	gold quality
body of pancreas	UBERON:0001150	95.22	gold quality
ganglionic eminence	UBERON:0004023	94.59	gold quality
right atrium auricular region	UBERON:0006631	94.35	gold quality
smooth muscle tissue	UBERON:0001135	94.34	gold quality
heart left ventricle	UBERON:0002084	94.18	gold quality
tibial artery	UBERON:0007610	94.06	gold quality
popliteal artery	UBERON:0002250	94.05	gold quality
skin of leg	UBERON:0001511	93.83	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	93.76	gold quality
tibial nerve	UBERON:0001323	93.67	gold quality
skin of abdomen	UBERON:0001416	93.66	gold quality
right adrenal gland cortex	UBERON:0035827	93.63	gold quality
rectum	UBERON:0001052	93.61	gold quality
muscle layer of sigmoid colon	UBERON:0035805	93.53	gold quality
cardiac ventricle	UBERON:0002082	93.33	gold quality
lower esophagus	UBERON:0013473	93.33	gold quality
lower esophagus muscularis layer	UBERON:0035833	93.32	gold quality
omental fat pad	UBERON:0010414	93.21	gold quality
pancreas	UBERON:0001264	93.18	gold quality
aorta	UBERON:0000947	93.17	gold quality
peritoneum	UBERON:0002358	93.10	gold quality
descending thoracic aorta	UBERON:0002345	93.09	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.55

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
ATP13A2	Activation

Upstream regulators (CollecTRI, top): AHR, EPAS1, ESR2, ETV4, HIF1A, SIRT1, UNCX

miRNA regulators (miRDB)

212 targeting EGLN1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4533	100.00	69.48	2758
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-520G-5P	99.99	66.76	658
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 16.6% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• PHD2 is the critical oxygen sensor setting the low steady-state levels of HIF-1alpha in normoxia. It is upregulated by oxygen. (PMID:12912907)
• we demonstrate that PHD2 is not affected by overexpression or downregulation of HIF-2alpha (PMID:15156561)
• PHD1, PHD2, and PHD3 have roles in the regulation of hypoxia-inducible factor (PMID:15247232)
• The phd2 gene is transcribed exclusively from the downstream promoter that contains a functional hypoxia-responsive, cis-regulatory element. (PMID:15563275)
• the N-terminal region of PHD2 contains a Myeloid translocation protein 8, Nervy, and DEAF1 (MYND)-type zinc finger domain, whereas the catalytic domain is located in its C-terminal region; the MYND domain inhibits the catalytic activity of PHD2 (PMID:16155211)
• Accumulated EGLN1 in hypoxia acts as a negative-feedback mechanism to modulate HIF-1alpha target gene expression. (PMID:16157596)
• EGLN1 can be considered as a candidate tumor suppressor on chromosome 1q, and our observation could open the new aspect in exploring the machinery of senescence induction associated with hypoxia-inducible factor 1, alpha signal transduction (PMID:16161047)
• Critical for normal regulation of hypoxia-inducible factor. (PMID:16407130)
• PHD2 shows strongly elevated expression both at the mRNA and protein level in head and neck squamous cell carcinoma. (PMID:16489060)
• Crystal structures of the catalytic domain of human PHD2 were described. (PMID:16782814)
• a novel mechanism by which a growth factor controls hypoxia-inducible transcription factor-1 (HIF-1alpha)stability, and thereby drives the expression of specific genes, through the regulation of PHD2 levels (PMID:16815840)
• A recombinant form of a human prolyl-4-hydroxylase (PHD2) was characterised and shown to have an unexpectedly high affinity for, and to copurify with endogenous levels of, its Fe(ii) cofactor and 2-oxoglutarate cosubstrate. (PMID:16880998)
• PHD2 induction is an underlying mechanism of NO-induced degradation of HIF-1alpha (PMID:17060326)
• Data suggest that the peptidyl prolyl cis/trans isomerase FKBP38 determines hypoxia-inducible transcription factor prolyl-4-hydroxylase PHD2 protein stability. (PMID:17353276)
• PHD2 mutation is associated with abnormal erythrocytosis (PMID:17579185)
• PHD inhibitors preferentially bind to the active site of PHD2 and stabilize HIF activity, induce angiogenesis and protect against cerebral ischemia. (PMID:17932321)
• Genetic defects are first frameshift and nonsense mutations reported in PHD2 gene and suggest that a decreased prolyl hydroxylase activity disturbing the oxygen-sensing pathway might be the cause of erythrocytosis. (PMID:17933562)
• PHD2 does not mediate the TCDD-mediated HIF-1 alpha destabilization nor control the interference of AhR and HIF-1 alpha pathways. (PMID:18072750)
• Chronic hypoxia not only increases the pool of PHDs but also overactivates the three PHD isoforms. (PMID:18347341)
• PHD2 has a role in modulating tumor-forming potential (PMID:18505927)
• suggest a role for PHD2 as a decisive oxygen sensor of the hypoxia-inducible factor degradation pathway within the cell nucleus (PMID:18776187)
• Biochemical characterization of PHD2 variants associated with polycythemia is reported. (PMID:18834144)
• These data suggest that the effects of Egln1 knockdown depend on the status of pVHL and can be correlated with effects on Rpb1. (PMID:19159641)
• Given the role of PHD2 as an oxygen sensor in mammalian cells, these results raise the possibility that PHD2 links vascular smooth muscle cell proliferation to O(2) availability (PMID:19304911)
• Results describe the localization signal of HIF-prolyl hydroxylases (PHDs) 1-3, and their intracellular localization in response to hypoxia. (PMID:19339211)
• PHD2 plays a critical role in regulating tumor angiogenesis. (PMID:19477431)
• Data indicate that PHD2 protein stability is regulated by a ubiquitin-independent proteasomal pathway involving FKBP38 as adaptor protein that mediates proteasomal interaction. (PMID:19546213)
• study on the reactivity of the cysteines in the catalytic domain of PHD2; results reveal that of the seven cysteinyl residues in the catalytic domain, Cys201 is the most nucleophilic (PMID:19563769)
• these findings provide new insights into the mechanisms of the regulation of the oxygen sensor cascade of PHD1 and PHD2 in different cellular compartments. (PMID:19631610)
• nuclear PHD2 expression may act as a surrogate marker for radiation resistance in squamous cell cancer of the head and neck (PMID:19639506)
• BRCA1 tumours correlate with a HIF-1alpha phenotype and have a poor prognosis through modulation of hydroxylase enzyme profile expression. (PMID:19724277)
• EGLN1 CPG-island methylation was not observed in various plasma cell dyscrasias. (PMID:19737309)
• Its mutation accelerates the transcription of EPO gene by stabilizing HIF-alpha protein. (review) (PMID:19915370)
• Regulation and expression of both PHD2 and HIF-1a are important to the biology of sarcomas, and loss of PHD2 function has an additional adverse effect in the prognosis of sarcomas in tumors expressing HIF-1a. (PMID:20026900)
• our findings recognize the PHD/HIF regulatory axis as a novel therapeutic target to disable a tumor’s ability to adjust to hypoxic conditions and control cell survival (PMID:20028863)
• Nuclear PHD2 localization promotes malignant cancer phenotype. (PMID:20156434)
• Depletion of PHD2 results in greater HIF-2alpha levels and enhances SOX9-induced cartilage matrix production. (PMID:20404338)
• genome-wide scans reveal positive selection in regions with genes whose products likely involved in high-altitude adaptation; positively selected haplotypes of EGLN1 and PPARA associated with decreased hemoglobin unique to highland population of Tibet (PMID:20466884)
• Methylation-induced epigenetic silencing of PHD1, PHD2, PHD3 and FIH is unlikely to underlie up-regulated HIF-1alpha expression in human breast cancer but may play a role in other tumour types. (PMID:20727020)
• PHD2 affects cell migration and F-actin formation via RhoA/rho-associated kinase-dependent cofilin phosphorylation (PMID:20801873)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	egln1b	ENSDARG00000004632
danio_rerio	egln1a	ENSDARG00000038996
danio_rerio	egln1b	ENSDARG00000105156
mus_musculus	Egln1	ENSMUSG00000031987
caenorhabditis_elegans		WBGENE00001178

Paralogs (2): EGLN3 (ENSG00000129521), EGLN2 (ENSG00000269858)

Protein

Protein identifiers

Egl nine homolog 1 — Q9GZT9 (reviewed: Q9GZT9)

Alternative names: Hypoxia-inducible factor prolyl hydroxylase 2, Prolyl hydroxylase domain-containing protein 2, SM-20

All UniProt accessions (6): A0A590UJ78, A0A590UJD6, A0A590UJT7, A0A590UJZ0, Q9GZT9, R4SCQ0

UniProt curated annotations — full annotation on UniProt →

Function. Cellular oxygen sensor that catalyzes, under normoxic conditions, the post-translational formation of 4-hydroxyproline in hypoxia-inducible factor (HIF) alpha proteins. Hydroxylates a specific proline found in each of the oxygen-dependent degradation (ODD) domains (N-terminal, NODD, and C-terminal, CODD) of HIF1A. Also hydroxylates HIF2A. Has a preference for the CODD site for both HIF1A and HIF1B. Hydroxylated HIFs are then targeted for proteasomal degradation via the von Hippel-Lindau ubiquitination complex. Under hypoxic conditions, the hydroxylation reaction is attenuated allowing HIFs to escape degradation resulting in their translocation to the nucleus, heterodimerization with HIF1B, and increased expression of hypoxy-inducible genes. EGLN1 is the most important isozyme under normoxia and, through regulating the stability of HIF1, involved in various hypoxia-influenced processes such as angiogenesis in retinal and cardiac functionality. Target proteins are preferentially recognized via a LXXLAP motif.

Subunit / interactions. Monomer. Interacts with ING4; the interaction inhibits the hydroxylation of HIF alpha proteins. Interacts with PTGES3 (via PXLE motif); thereby recruiting EGLN1 to the HSP90 pathway to facilitate HIF alpha proteins hydroxylation. Interacts with LIMD1. Found in a complex composed of LIMD1, VHL, EGLN1/PHD2, ELOB and CUL2. Interacts with EPAS1. Interacts with CBFA2T3. Interacts with HIF1A.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. According to PubMed:11056053, widely expressed with highest levels in skeletal muscle and heart, moderate levels in pancreas, brain (dopaminergic neurons of adult and fetal substantia nigra) and kidney, and lower levels in lung and liver. According to PubMed:12351678 widely expressed with highest levels in brain, kidney and adrenal gland. Expressed in cardiac myocytes, aortic endothelial cells and coronary artery smooth muscle. According to PubMed:12788921; expressed in adult and fetal heart, brain, liver, lung, skeletal muscle and kidney. Also expressed in placenta. Highest levels in adult heart, brain, lung and liver and fetal brain, heart spleen and skeletal muscle.

Post-translational modifications. S-nitrosylation inhibits the enzyme activity up to 60% under aerobic conditions. Chelation of Fe(2+) has no effect on the S-nitrosylation. It is uncertain whether nitrosylation occurs on Cys-323 or Cys-326.

Disease relevance. Erythrocytosis, familial, 3 (ECYT3) [MIM:609820] An autosomal dominant disorder characterized by elevated serum hemoglobin and hematocrit, and normal serum erythropoietin levels. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Following exposure to hypoxia, activated in HeLa cells but not in cardiovascular cells.

Cofactor. Binds 1 Fe(2+) ion per subunit.

Domain organisation. The beta(2)beta(3) ‘finger-like’ loop domain is important for substrate (HIFs’ CODD/NODD) selectivity.

Polymorphism. Variations in EGLN1 are associated with adaptation to high altitude. High-altitude hypoxia (reduced inspired oxygen tension due to decreased barometric pressure) exerts severe physiological stress on the human body and leads to an elevation of hematocrit levels and an increased number of erythrocytes (polycythemia) in non-adapted individuals. Genetic variations in EGLN1 contribute to adaptation to high altitute by maintaining hematocrit levels comparable to those for populations living at sea level and are present in two high-altitude regions where humans have lived for millennia, the Andean Altiplano and the Tibetan Plateau. Variants Glu-4 and Ser-127, which are frequently associated together and are present in the majority of Tibetan populations, participate in adaptation to high altitude. Molecular mechanisms explaining this adaptation are however unclear. According to a report, variants Glu-4 and Ser-127 lead to decreased interaction with PTGES3 and subsequent decrease of HIF alpha proteins degradation. According to a second report, Glu-4 and Ser-127 haplotype enhances the catalytic activity under hypoxic conditions, promoting increased HIF alpha proteins degradation, thereby abrogating hypoxia-induced and HIF alpha-mediated augmentation of erythropoiesis and protecting Tibetans from polycythemia at high altitude.

Miscellaneous. Inactive isoform.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9GZT9-1	1	yes
Q9GZT9-2	2
Q9GZT9-3	3

RefSeq proteins (3): NP_001364189, NP_001364190, NP_071334* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002893	Znf_MYND	Domain
IPR005123	Oxoglu/Fe-dep_dioxygenase_dom	Domain
IPR006620	Pro_4_hyd_alph	Domain
IPR044862	Pro_4_hyd_alph_FE2OG_OXY	Domain
IPR051559	HIF_prolyl_hydroxylases	Family

Pfam: PF01753, PF13640

Enzyme classification (BRENDA):

• EC 1.14.11.2 — procollagen-proline 4-dioxygenase (BRENDA: 37 organisms, 182 substrates, 264 inhibitors, 251 Km, 44 kcat entries)
• EC 1.14.11.29 — hypoxia-inducible factor-proline dioxygenase (BRENDA: 7 organisms, 73 substrates, 125 inhibitors, 61 Km, 16 kcat entries)

Substrate kinetics (BRENDA)

101 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
2-OXOGLUTARATE	0.001–1	37
POLY(L-PROLINE)	0.0002–1.59	26
(L-PRO-L-PRO-GLY)10	0.015–2.9	15
(PRO-PRO-GLY)10	0.011–1.27	15
POLY(L-PRO)	0.002–0.65	15
FE2+	0.0004–0.016	9
O2	0.03–1.5	9
ASCORBATE	0.14–0.37	8
(L-PRO-L-PRO-GLY)5	0.12–1.8	6
PROTOCOLLAGEN	—	6
2-OXOGLUTARATE	0.0007–0.06	6
HYPOXIA-INDUCIBLE FACTOR-L-PROLINE	0.001–0.067	5
O2	0.1–0.76	5
(L-PRO-L-ALA-L-PRO-L-LYS)3	0.09–0.31	4
(SER-PRO)5	0.14–0.78	4

Catalyzed reactions (Rhea), 1 shown:

• L-prolyl-[hypoxia-inducible factor alpha subunit] + 2-oxoglutarate + O2 = trans-4-hydroxy-L-prolyl-[hypoxia-inducible factor alpha subunit] + succinate + CO2 (RHEA:48400)

UniProt features (75 total): strand 16, binding site 12, mutagenesis site 11, helix 9, modified residue 8, sequence variant 4, region of interest 4, compositionally biased region 3, splice variant 2, turn 2, initiator methionine 1, chain 1, domain 1, zinc finger region 1

Structure

Experimental structures (PDB)

64 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
7Q5V	X-RAY DIFFRACTION	1.17
7Q5X	X-RAY DIFFRACTION	1.21
8Q64	X-RAY DIFFRACTION	1.36
8Q6E	X-RAY DIFFRACTION	1.37
8RV1	X-RAY DIFFRACTION	1.39
6QGV	X-RAY DIFFRACTION	1.4
8Q6D	X-RAY DIFFRACTION	1.4
6YW1	X-RAY DIFFRACTION	1.46
8Q5S	X-RAY DIFFRACTION	1.49
6YW4	X-RAY DIFFRACTION	1.53
4BQY	X-RAY DIFFRACTION	1.53
6NMQ	X-RAY DIFFRACTION	1.58
2HBT	X-RAY DIFFRACTION	1.6
8RUT	X-RAY DIFFRACTION	1.62
8RUV	X-RAY DIFFRACTION	1.66
2G19	X-RAY DIFFRACTION	1.7
3OUI	X-RAY DIFFRACTION	1.7
5LB6	X-RAY DIFFRACTION	1.7
5LBB	X-RAY DIFFRACTION	1.7
4UWD	X-RAY DIFFRACTION	1.72
5LBE	X-RAY DIFFRACTION	1.75
4BQW	X-RAY DIFFRACTION	1.79
4BQX	X-RAY DIFFRACTION	1.79
6ZBO	X-RAY DIFFRACTION	1.79
6YVX	X-RAY DIFFRACTION	1.8
7UJV	X-RAY DIFFRACTION	1.8
7UMP	X-RAY DIFFRACTION	1.8
5L9R	X-RAY DIFFRACTION	1.81
8Z31	X-RAY DIFFRACTION	1.81
5LBC	X-RAY DIFFRACTION	1.82

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9GZT9-F1	73.81	0.50

Functional residue map

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

Ligand- & substrate-binding residues (12): 21; 24; 33; 36; 42; 46; 54; 58; 313; 315; 374; 383

Post-translational modifications (8): 2, 12, 125, 201, 208, 302, 323, 326

Mutagenesis-validated functional residues (11):

Position	Phenotype
201	little change in enzyme activity.
208	little change in enzyme activity.
252	reduced c-terminal odd domain (codd) hydroxylation of hif1a.
254	reduced c-terminal odd domain (codd) hxdroxylation of hif1a.
266	little change in enzyme activity.
283	little change in enzyme activity.
302	slight increase in enzyme activity.
303	no effect.
323	little change in enzyme activity.
326	slight increase in enzyme activity.
383	reduces enzyme activity by 95%.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-1234176	Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha

MSigDB gene sets: 278 (showing top): GOBP_CARDIAC_CHAMBER_DEVELOPMENT, GOBP_LABYRINTHINE_LAYER_DEVELOPMENT, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, FREAC2_01, GOBP_MUSCLE_TISSUE_DEVELOPMENT, GOBP_CARDIAC_SEPTUM_DEVELOPMENT, GOBP_VENTRICULAR_SEPTUM_MORPHOGENESIS, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_HEART_TRABECULA_MORPHOGENESIS, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_PAIRED_DONORS_WITH_INCORPORATION_OR_REDUCTION_OF_MOLECULAR_OXYGEN, GOBP_CARDIAC_CHAMBER_MORPHOGENESIS, NKX25_02, GCANCTGNY_MYOD_Q6, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN

GO Biological Process (15): response to hypoxia (GO:0001666), intracellular iron ion homeostasis (GO:0006879), intracellular oxygen homeostasis (GO:0032364), regulation of neuron apoptotic process (GO:0043523), regulation of angiogenesis (GO:0045765), positive regulation of transcription by RNA polymerase II (GO:0045944), cardiac muscle tissue morphogenesis (GO:0055008), heart trabecula formation (GO:0060347), ventricular septum morphogenesis (GO:0060412), labyrinthine layer development (GO:0060711), cellular response to hypoxia (GO:0071456), response to nitric oxide (GO:0071731), regulation of modification of postsynaptic structure (GO:0099159), regulation protein catabolic process at postsynapse (GO:0140252), negative regulation of hypoxia-inducible factor-1alpha signaling pathway (GO:1902072)

GO Molecular Function (15): enzyme inhibitor activity (GO:0004857), ferrous iron binding (GO:0008198), zinc ion binding (GO:0008270), 2-oxoglutarate-dependent dioxygenase activity (GO:0016706), enzyme binding (GO:0019899), L-ascorbic acid binding (GO:0031418), peptidyl-proline dioxygenase activity (GO:0031543), peptidyl-proline 4-dioxygenase activity (GO:0031545), hypoxia-inducible factor-proline dioxygenase activity (GO:0160082), iron ion binding (GO:0005506), protein binding (GO:0005515), oxidoreductase activity (GO:0016491), oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen (GO:0016705), metal ion binding (GO:0046872), dioxygenase activity (GO:0051213)

GO Cellular Component (5): nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), postsynaptic density (GO:0014069), glutamatergic synapse (GO:0098978)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Cellular response to hypoxia	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
catalytic activity	2
transition metal ion binding	2
oxidoreductase activity	2
cellular anatomical structure	2
response to stress	1
response to decreased oxygen levels	1
intracellular monoatomic cation homeostasis	1
inorganic ion homeostasis	1
intracellular chemical homeostasis	1
regulation of apoptotic process	1
neuron apoptotic process	1
angiogenesis	1
regulation of anatomical structure morphogenesis	1
regulation of vasculature development	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
heart morphogenesis	1
cardiac muscle tissue development	1
muscle tissue morphogenesis	1
cardiac chamber morphogenesis	1
trabecula formation	1
heart trabecula morphogenesis	1
ventricular septum development	1
cardiac septum morphogenesis	1
embryonic placenta development	1
anatomical structure development	1
response to hypoxia	1
cellular response to stress	1
cellular response to decreased oxygen levels	1
response to nitrogen compound	1
response to oxygen-containing compound	1
modification of postsynaptic structure	1
regulation of modification of synaptic structure	1
postsynapse	1
regulation protein catabolic process at synapse	1
hypoxia-inducible factor-1alpha signaling pathway	1
negative regulation of cellular response to hypoxia	1
regulation of hypoxia-inducible factor-1alpha signaling pathway	1
negative regulation of intracellular signal transduction	1

Protein interactions and networks

STRING

1722 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EGLN1	HIF1A	Q16665	982
EGLN1	EPAS1	Q99814	969
EGLN1	VHL	P40337	950
EGLN1	ARNT	P27540	922
EGLN1	OS9	Q13438	921
EGLN1	EPO	P01588	851
EGLN1	ELOC	Q15369	846
EGLN1	HIF3A	Q9Y2N7	841
EGLN1	CDC34	P49427	806
EGLN1	EIF5B	O60841	802
EGLN1	HIF1AN	Q9NWT6	796
EGLN1	LIMD1	Q9UGP4	740
EGLN1	H3-3A	P06351	732
EGLN1	P4HA1	P13674	730
EGLN1	SIAH2	O43255	728

IntAct

187 interactions, top by confidence:

A	B	Type	Score
EGLN1	HIF1A	psi-mi:“MI:0210”(hydroxylation reaction)	0.860
HIF1A	EGLN1	psi-mi:“MI:0210”(hydroxylation reaction)	0.860
EGLN1	HIF1A	psi-mi:“MI:0915”(physical association)	0.860
EGLN1	HIF1A	psi-mi:“MI:0414”(enzymatic reaction)	0.860
VHL	HIF1A	psi-mi:“MI:0915”(physical association)	0.660
OS9	HIF1A	psi-mi:“MI:0914”(association)	0.650
EPAS1	EGLN1	psi-mi:“MI:0915”(physical association)	0.630
FKBP8	EGLN1	psi-mi:“MI:0915”(physical association)	0.630
EGLN1	EPAS1	psi-mi:“MI:0915”(physical association)	0.630
EGLN1	FKBP8	psi-mi:“MI:0915”(physical association)	0.630
FKBP8	EGLN1	psi-mi:“MI:0403”(colocalization)	0.630
IGF1R	PIK3R2	psi-mi:“MI:2364”(proximity)	0.590
EEF1AKMT1	EEF1A1	psi-mi:“MI:0914”(association)	0.530
PTGES3	AIP	psi-mi:“MI:0914”(association)	0.530
EEF1AKMT1	TTLL12	psi-mi:“MI:0914”(association)	0.530
	EGLN1	psi-mi:“MI:0915”(physical association)	0.500
OS9	EGLN1	psi-mi:“MI:0915”(physical association)	0.500
SDCBP	EGLN1	psi-mi:“MI:0407”(direct interaction)	0.440
EGLN1	DLG3	psi-mi:“MI:0407”(direct interaction)	0.440
EGLN1	TIAM2	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (198): PLD1 (Affinity Capture-Western), PLD1 (Reconstituted Complex), HIF1A (Affinity Capture-Western), EGLN1 (Affinity Capture-Western), EGLN1 (Affinity Capture-MS), EGLN1 (Affinity Capture-MS), EGLN1 (Affinity Capture-MS), EGLN1 (Affinity Capture-MS), EGLN1 (Affinity Capture-MS), EGLN1 (Proximity Label-MS), PLD2 (Affinity Capture-Western), EGLN1 (Affinity Capture-Western), EGLN1 (Affinity Capture-Western), HIF1A (Affinity Capture-Western), GPLD1 (Affinity Capture-Western)

ESM2 similar proteins: D3YXJ0, D3ZVP7, E9PUQ8, M9MRI4, O00562, O14827, O35954, O70143, O75689, O76902, O95248, P08240, P11862, P34657, Q02280, Q05B78, Q15057, Q16760, Q17QP1, Q29RQ5, Q2I6J0, Q2KI13, Q38JA7, Q4R584, Q505D9, Q5F3R2, Q5RFL4, Q5U2N3, Q5W7F2, Q5ZK62, Q64398, Q68FU1, Q6NNF2, Q6NVJ5, Q6ZPE2, Q6ZTA4, Q810J8, Q86XP1, Q8C7M3, Q8VCM3

Diamond homologs: A9CPT4, C3RZA1, D3ZKV9, E1C5V0, F1QN74, F1RET2, O74467, P97443, Q0P585, Q12529, Q3TYX3, Q4VC12, Q5BJI7, Q5F3V0, Q5R5X9, Q5RGL7, Q5UNT8, Q5ZIZ2, Q6C9E7, Q6GMV2, Q6GN68, Q6GPQ4, Q7M6Z3, Q7TSV3, Q7ZXV5, Q8BTK5, Q8IYR2, Q8NB12, Q8R5A0, Q91YE3, Q96E35, Q9BXT4, Q9CQG3, Q9CWR2, Q9D5Z5, Q9GZT9, Q9H7B4, Q9N3Q8, Q9NRG4, A3M0J3

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
dimethyloxalylglycine	“down-regulates activity”	EGLN1	“chemical inhibition”
EGLN1	“down-regulates quantity by destabilization”	HIF1A	hydroxylation
Hypoxia	down-regulates	EGLN1
EIF2S2	“up-regulates quantity”	EGLN1	“translation regulation”
PRKAA1	“down-regulates activity”	EGLN1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 140 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Ras activation upon Ca2+ influx through NMDA receptor	6	35.0×	2e-06
Unblocking of NMDA receptors, glutamate binding and activation	5	27.8×	7e-05
Negative regulation of NMDA receptor-mediated neuronal transmission	5	27.8×	7e-05
Long-term potentiation	5	24.3×	1e-04
Assembly and cell surface presentation of NMDA receptors	9	23.3×	3e-08
Neurexins and neuroligins	10	20.1×	3e-08
Protein-protein interactions at synapses	6	16.3×	1e-04
RHOB GTPase cycle	5	7.9×	7e-03

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	10	44.4×	1e-11
protein localization to synapse	6	35.1×	3e-06
receptor clustering	7	33.4×	6e-07
regulation of postsynaptic membrane neurotransmitter receptor levels	7	26.5×	2e-06
protein-containing complex assembly	10	8.7×	3e-05
cell-cell adhesion	11	8.5×	1e-05
actin cytoskeleton organization	9	5.4×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

1294 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	12
Likely pathogenic	1
Uncertain significance	690
Likely benign	465
Benign	60

Top pathogenic / likely-pathogenic (13)

Variant ID	HGVS	Classification
1048777	NM_022051.3(EGLN1):c.1010dup (p.Val338fs)	Pathogenic
2864415	NM_022051.3(EGLN1):c.494del (p.Pro165fs)	Pathogenic
2901944	NM_022051.3(EGLN1):c.774G>A (p.Trp258Ter)	Pathogenic
3608822	NM_022051.3(EGLN1):c.773G>A (p.Trp258Ter)	Pathogenic
3723092	NM_022051.3(EGLN1):c.373_403del (p.Ser125fs)	Pathogenic
4356	NM_022051.3(EGLN1):c.1112G>A (p.Arg371His)	Pathogenic
4357	NM_022051.3(EGLN1):c.1121A>G (p.His374Arg)	Pathogenic
4723205	NM_022051.3(EGLN1):c.1133del (p.Pro378fs)	Pathogenic
4724899	NM_022051.3(EGLN1):c.174C>A (p.Cys58Ter)	Pathogenic
4732941	NM_022051.3(EGLN1):c.1137del (p.Tyr380fs)	Pathogenic
4733674	NM_022051.3(EGLN1):c.1044_1045insATTTTCCAGAAAATTTCCAGAA (p.Gly349fs)	Pathogenic
649669	NM_022051.3(EGLN1):c.461C>A (p.Ser154Ter)	Pathogenic
4542336	NM_022051.3(EGLN1):c.1012-2A>C	Likely pathogenic

SpliceAI

938 predictions. Top by Δscore:

Variant	Effect	Δscore
1:231366473:CACCT:C	acceptor_loss	1.0000
1:231366474:ACC:A	acceptor_loss	1.0000
1:231366476:C:T	acceptor_loss	1.0000
1:231366477:T:A	acceptor_loss	1.0000
1:231370556:TACTA:T	donor_loss	1.0000
1:231370561:C:A	donor_gain	1.0000
1:231370561:C:CA	donor_loss	1.0000
1:231370586:T:TA	donor_gain	1.0000
1:231370694:CTTAC:C	acceptor_gain	1.0000
1:231373975:CATA:C	donor_loss	1.0000
1:231373976:ATAC:A	donor_loss	1.0000
1:231373977:TA:T	donor_loss	1.0000
1:231373978:A:C	donor_loss	1.0000
1:231374096:TGGC:T	acceptor_gain	1.0000
1:231366473:CAC:C	acceptor_gain	0.9900
1:231366476:C:CC	acceptor_gain	0.9900
1:231370695:TTAC:T	acceptor_gain	0.9900
1:231370696:TAC:T	acceptor_gain	0.9900
1:231370699:C:A	acceptor_loss	0.9900
1:231370700:T:G	acceptor_loss	0.9900
1:231372630:TCAA:T	donor_gain	0.9900
1:231374014:CATG:C	donor_gain	0.9900
1:231374015:A:C	donor_gain	0.9900
1:231374097:GGCCT:G	acceptor_loss	0.9900
1:231374098:GC:G	acceptor_gain	0.9900
1:231374099:CC:C	acceptor_gain	0.9900
1:231374099:CCT:C	acceptor_loss	0.9900
1:231374100:C:CC	acceptor_gain	0.9900
1:231374100:C:G	acceptor_loss	0.9900
1:231374101:T:G	acceptor_loss	0.9900

AlphaMissense

2782 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:231367589:G:T	A399D	1.000
1:231367590:C:G	A399P	1.000
1:231367597:T:A	R396S	1.000
1:231367597:T:G	R396S	1.000
1:231367598:C:A	R396I	1.000
1:231367598:C:G	R396T	1.000
1:231367601:T:A	E395V	1.000
1:231367610:T:A	D392V	1.000
1:231367612:A:C	F391L	1.000
1:231367612:A:T	F391L	1.000
1:231367613:A:C	F391C	1.000
1:231367613:A:G	F391S	1.000
1:231367614:A:C	F391V	1.000
1:231367614:A:G	F391L	1.000
1:231367614:A:T	F391I	1.000
1:231367616:T:C	Y390C	1.000
1:231367616:T:G	Y390S	1.000
1:231367617:A:C	Y390D	1.000
1:231367617:A:G	Y390H	1.000
1:231367618:C:A	W389C	1.000
1:231367618:C:G	W389C	1.000
1:231367619:C:A	W389L	1.000
1:231367619:C:G	W389S	1.000
1:231367620:A:G	W389R	1.000
1:231367620:A:T	W389R	1.000
1:231367622:A:T	V388D	1.000
1:231367625:G:A	T387I	1.000
1:231367625:G:T	T387N	1.000
1:231367626:T:G	T387P	1.000
1:231367628:A:C	I386R	1.000

dbSNP variants (sampled 300 via entrez): RS1000055324 (1:231422729 T>A), RS1000169953 (1:231380910 T>C), RS1000194717 (1:231419500 A>G), RS1000199918 (1:231372235 A>C), RS1000309510 (1:231372680 A>G), RS1000316521 (1:231422580 G>GGGCAGCGC), RS1000325764 (1:231408206 G>C,T), RS1000353893 (1:231396342 C>T), RS1000378220 (1:231408548 A>G), RS1000429574 (1:231364412 G>A,T), RS1000451167 (1:231378986 C>G), RS1000596764 (1:231401820 T>A), RS1000608095 (1:231386059 G>T), RS1000628933 (1:231394751 G>A), RS1000682677 (1:231395014 T>C)

Disease associations

OMIM: gene MIM:606425 | disease phenotypes: MIM:609820, MIM:613659

GenCC curated gene-disease

Disease	Classification	Inheritance
erythrocytosis, familial, 3	Definitive	Autosomal dominant
EGLN1-related erythrocytosis and pheochromocytoma/paraganglioma predisposition	Definitive	Autosomal dominant
autosomal dominant secondary polycythemia	Supportive	Autosomal dominant
hereditary pheochromocytoma-paraganglioma	Limited	Autosomal dominant
hemoglobin, high altitude adaptation	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
EGLN1-related erythrocytosis and pheochromocytoma/paraganglioma predisposition	Definitive	AD

Mondo (6): erythrocytosis, familial, 3 (MONDO:0012353), gastric cancer (MONDO:0001056), hereditary pheochromocytoma-paraganglioma (MONDO:0017366), (MONDO:0044274), EGLN1-related erythrocytosis and pheochromocytoma/paraganglioma predisposition (MONDO:1060184), (MONDO:0016599)

Orphanet (1): Autosomal dominant secondary polycythemia (Orphanet:247511)

HPO phenotypes

5 total (5 of 5 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0001871	Abnormality of blood and blood-forming tissues
HP:0001898	Increased red blood cell mass
HP:0001899	Increased hematocrit
HP:0001900	Increased circulating hemoglobin concentration

GWAS associations

15 associations (top):

Study	Trait	p-value
GCST004601_12	Red blood cell count	2.000000e-09
GCST004601_13	Red blood cell count	8.000000e-20
GCST004604_18	Hematocrit	8.000000e-16
GCST004604_19	Hematocrit	8.000000e-25
GCST004615_87	Hemoglobin concentration	2.000000e-24
GCST006054_4	High altitude adaptation	6.000000e-15
GCST009391_1315	Metabolite levels	4.000000e-06
GCST010083_267	Hemoglobin levels	8.000000e-44
GCST011381_8	Cutaneous mastocytosis	8.000000e-07
GCST90002383_153	Hematocrit	3.000000e-31
GCST90002383_154	Hematocrit	9.000000e-50
GCST90002384_32	Hemoglobin	2.000000e-25
GCST90002384_33	Hemoglobin	3.000000e-48
GCST90002403_69	Red blood cell count	1.000000e-22
GCST90002403_70	Red blood cell count	2.000000e-43

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004305	erythrocyte count
EFO:0004348	hematocrit
EFO:0004509	hemoglobin measurement
EFO:0009105	high altitude adaptation
EFO:0010519	pantothenic acid measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C565221	Erythrocytosis, Familial, 3 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3831261 (PROTEIN FAMILY), CHEMBL5697 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

11 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,969,800 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL2338329	ROXADUSTAT	4	1,063
CHEMBL3544988	DAPRODUSTAT	4	308
CHEMBL3646221	VADADUSTAT	4	533
CHEMBL4297619	ENARODUSTAT	3	109
CHEMBL4650314	DESIDUSTAT	3	254
CHEMBL503160	FUMARIC ACID	3	845,433
CHEMBL576	SUCCINIC ACID	3	1,121,639
CHEMBL3115298	IZILENDUSTAT	2	51
CHEMBL3646118	MOLIDUSTAT	2	354
CHEMBL3931782	MOLIDUSTAT SODIUM	1	34
CHEMBL4162752	DDO-3055	1	22

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Prolyl hydroxylases

Most potent curated ligand interactions (6 total), top 6:

Ligand	Action	Affinity	Parameter
compound 6ee [PMID: 22364528]	Inhibition	9.7	pIC50
IOX2	Inhibition	7.66	pIC50
vadadustat	Inhibition	7.54	pIC50
DDO-3055	Inhibition	7.19	pIC50
enarodustat	Inhibition	6.66	pIC50
IOX1	Inhibition	4.48	pIC50

Binding affinities (BindingDB)

1110 measured of 1163 human assays (1171 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
(S)-6-(4-(4-cyanophenyl)-5-hydroxy-1H-pyrazol-1-yl)-N-(4-methoxybutan-2-yl)nicotinamide	IC50	1.78 nM	US-10407409: 6-(5-hydroxy-1H-pyrazol-1-yl)nicotinamide inhibitors of PHD
6-(4-(4-cyano-2-methylphenyl)-5-hydroxy-1H-pyrazol-1-yl)-N,N-dimethylnicotinamide	IC50	2.14 nM	US-10407409: 6-(5-hydroxy-1H-pyrazol-1-yl)nicotinamide inhibitors of PHD
2-fluoro-4-(5-hydroxy-1-(5-(morpholine-4-carbonyl)pyridin-2-yl)-1H-pyrazol-4-yl)-5-methylbenzonitrile	IC50	2.24 nM	US-10407409: 6-(5-hydroxy-1H-pyrazol-1-yl)nicotinamide inhibitors of PHD
2-fluoro-4-(5-hydroxy-1-(5-(4-methyl-4,7-diazaspiro[2.5]octane-7-carbonyl)pyridin-2-yl)-1H-pyrazol-4-yl)-5-methylbenzonitrile	IC50	2.34 nM	US-10407409: 6-(5-hydroxy-1H-pyrazol-1-yl)nicotinamide inhibitors of PHD
4-(5-hydroxy-1-(5-(4-propylpiperazine-1-carbonyl)pyridin-2-yl)-1H-pyrazol-4-yl)-3-methylbenzonitrile	IC50	2.51 nM	US-10407409: 6-(5-hydroxy-1H-pyrazol-1-yl)nicotinamide inhibitors of PHD
(S)-6-(4-(4-cyano-2-methylphenyl)-5-hydroxy-1H-pyrazol-1-yl)-N-(4-methoxybutan-2-yl)nicotinamide	IC50	2.51 nM	US-10407409: 6-(5-hydroxy-1H-pyrazol-1-yl)nicotinamide inhibitors of PHD
2-fluoro-4-(5-hydroxy-1-(5-(4-methylpiperazine-1-carbonyl)pyridin-2-yl)-1H-pyrazol-4-yl)-5-methylbenzonitrile	IC50	2.57 nM	US-10407409: 6-(5-hydroxy-1H-pyrazol-1-yl)nicotinamide inhibitors of PHD
(S)-4-(1-(5-(3-((2,2-difluoroethyl)(methyl)amino)piperidine-1-carbonyl)pyridin-2-yl)-5-hydroxy-1H-pyrazol-4-yl)-2-fluoro-3-methylbenzonitrile	IC50	2.82 nM	US-10407409: 6-(5-hydroxy-1H-pyrazol-1-yl)nicotinamide inhibitors of PHD
2-fluoro-4-(5-hydroxy-1-(5-(4-methyl-4,7-diazaspiro[2.5]octane-7-carbonyl)pyridin-2-yl)-1H-pyrazol-4-yl)-3-methylbenzonitrile	IC50	2.88 nM	US-10407409: 6-(5-hydroxy-1H-pyrazol-1-yl)nicotinamide inhibitors of PHD
(R)-4-(1-(5-(3-((2,2-difluoroethyl)(methyl)amino)piperidine-1-carbonyl)pyridin-2-yl)-5-hydroxy-1H-pyrazol-4-yl)-2-fluoro-3-methylbenzonitrile	IC50	2.95 nM	US-10407409: 6-(5-hydroxy-1H-pyrazol-1-yl)nicotinamide inhibitors of PHD
(S)-4-(1-(5-(4-ethyl-3-methylpiperazine-1-carbonyl)pyridin-2-yl)-5-hydroxy-1H-pyrazol-4-yl)-2-fluoro-5-methylbenzonitrile	IC50	3.02 nM	US-10407409: 6-(5-hydroxy-1H-pyrazol-1-yl)nicotinamide inhibitors of PHD
4-(1-(5-(4-(2,2-difluoroethyl)piperazine-1-carbonyl)pyridin-2-yl)-5-hydroxy-1H-pyrazol-4-yl)-3-methylbenzonitrile	IC50	3.09 nM	US-10407409: 6-(5-hydroxy-1H-pyrazol-1-yl)nicotinamide inhibitors of PHD
4-(5-hydroxy-1-(5-(4-(2,2,2-trifluoroethyl)piperazine-1-carbonyl)pyridin-2-yl)-1H-pyrazol-4-yl)-3-methylbenzonitrile	IC50	3.16 nM	US-10407409: 6-(5-hydroxy-1H-pyrazol-1-yl)nicotinamide inhibitors of PHD
(S)-4-(1-(5-(3,4-dimethylpiperazine-1-carbonyl)pyridin-2-yl)-5-hydroxy-1H-pyrazol-4-yl)-2-fluoro-5-methylbenzonitrile	IC50	3.16 nM	US-10407409: 6-(5-hydroxy-1H-pyrazol-1-yl)nicotinamide inhibitors of PHD
(S)-4-(1-(5-(3,4-dimethylpiperazine-1-carbonyl)pyridin-2-yl)-5-hydroxy-1H-pyrazol-4-yl)-2-fluoro-3-methylbenzonitrile	IC50	3.16 nM	US-10407409: 6-(5-hydroxy-1H-pyrazol-1-yl)nicotinamide inhibitors of PHD
(R)-2-fluoro-4-(5-hydroxy-1-(5-(octahydropyrrolo[1,2-a]pyrazine-2-carbonyl)pyridin-2-yl)-1H-pyrazol-4-yl)-3-methylbenzonitrile	IC50	3.16 nM	US-10407409: 6-(5-hydroxy-1H-pyrazol-1-yl)nicotinamide inhibitors of PHD
6-(4-(4-cyano-3-fluoro-2-methylphenyl)-5-hydroxy-1H-pyrazol-1-yl)-N-(3-methoxypropyl)nicotinamide	IC50	3.24 nM	US-10407409: 6-(5-hydroxy-1H-pyrazol-1-yl)nicotinamide inhibitors of PHD
(R)-4-(1-(5-(4-ethyl-3-methylpiperazine-1-carbonyl)pyridin-2-yl)-5-hydroxy-1H-pyrazol-4-yl)-2-fluoro-5-methylbenzonitrile	IC50	3.31 nM	US-10407409: 6-(5-hydroxy-1H-pyrazol-1-yl)nicotinamide inhibitors of PHD
6-(4-(4-cyano-5-fluoro-2-methylphenyl)-5-hydroxy-1H-pyrazol-1-yl)-N-(3-methoxypropyl)nicotinamide	IC50	3.31 nM	US-10407409: 6-(5-hydroxy-1H-pyrazol-1-yl)nicotinamide inhibitors of PHD
US10407409, Example 288	IC50	3.31 nM	US-10407409: 6-(5-hydroxy-1H-pyrazol-1-yl)nicotinamide inhibitors of PHD
6-(4-(4-cyano-2-fluorophenyl)-5-hydroxy-1H-pyrazol-1-yl)-N-(4-methoxybutyl)nicotinamide	IC50	3.31 nM	US-10407409: 6-(5-hydroxy-1H-pyrazol-1-yl)nicotinamide inhibitors of PHD
2-fluoro-4-(5-hydroxy-1-(5-(morpholine-4-carbonyl)pyridin-2-yl)-1H-pyrazol-4-yl)-3-methylbenzonitrile	IC50	3.39 nM	US-10407409: 6-(5-hydroxy-1H-pyrazol-1-yl)nicotinamide inhibitors of PHD
(S)-2-fluoro-4-(5-hydroxy-1-(5-(3-(methyl(2,2,2-trifluoroethyl)amino)piperidine-1-carbonyl)pyridin-2-yl)-1H-pyrazol-4-yl)-3-methylbenzonitrile	IC50	3.39 nM	US-10407409: 6-(5-hydroxy-1H-pyrazol-1-yl)nicotinamide inhibitors of PHD
(S)-4-(1-(5-(4-ethyl-2-methylpiperazine-1-carbonyl)pyridin-2-yl)-5-hydroxy-1H-pyrazol-4-yl)-2-fluoro-3-methylbenzonitrile	IC50	3.39 nM	US-10407409: 6-(5-hydroxy-1H-pyrazol-1-yl)nicotinamide inhibitors of PHD
US10407409, Example 299	IC50	3.47 nM	US-10407409: 6-(5-hydroxy-1H-pyrazol-1-yl)nicotinamide inhibitors of PHD
(R)-6-(4-(4-cyanophenyl)-5-hydroxy-1H-pyrazol-1-yl)-N-(4-methoxybutan-2-yl)nicotinamide	IC50	3.47 nM	US-10407409: 6-(5-hydroxy-1H-pyrazol-1-yl)nicotinamide inhibitors of PHD
(R)-6-(4-(4-cyano-2-methylphenyl)-5-hydroxy-1H-pyrazol-1-yl)-N-(4-methoxybutan-2-yl)nicotinamide	IC50	3.55 nM	US-10407409: 6-(5-hydroxy-1H-pyrazol-1-yl)nicotinamide inhibitors of PHD
4-(5-hydroxy-1-(5-(3,3,4-trimethylpiperazine-1-carbonyl)pyridin-2-yl)-1H-pyrazol-4-yl)-3-methylbenzonitrile	IC50	3.63 nM	US-10407409: 6-(5-hydroxy-1H-pyrazol-1-yl)nicotinamide inhibitors of PHD
2-fluoro-4-(5-hydroxy-1-(5-(pyrrolidine-1-carbonyl)pyridin-2-yl)-1H-pyrazol-4-yl)-3-methylbenzonitrile	IC50	3.63 nM	US-10407409: 6-(5-hydroxy-1H-pyrazol-1-yl)nicotinamide inhibitors of PHD
(R)-4-(1-(5-(3,4-dimethylpiperazine-1-carbonyl)pyridin-2-yl)-5-hydroxy-1H-pyrazol-4-yl)-2-fluoro-5-methylbenzonitrile	IC50	3.63 nM	US-10407409: 6-(5-hydroxy-1H-pyrazol-1-yl)nicotinamide inhibitors of PHD
2-fluoro-4-(5-hydroxy-1-(5-(3-(piperidin-1-yl)azetidine-1-carbonyl)pyridin-2-yl)-1H-pyrazol-4-yl)-3-methylbenzonitrile	IC50	3.72 nM	US-10407409: 6-(5-hydroxy-1H-pyrazol-1-yl)nicotinamide inhibitors of PHD
6-(4-(4-cyano-2-methylphenyl)-5-hydroxy-1H-pyrazol-1-yl)-N-(1-(2,2,2-trifluoroethyl)piperidin-4-yl)nicotinamide	IC50	3.89 nM	US-10407409: 6-(5-hydroxy-1H-pyrazol-1-yl)nicotinamide inhibitors of PHD
6-(4-(4-cyano-2-methylphenyl)-5-hydroxy-1H-pyrazol-1-yl)-N-(2-oxaspiro[3.3]heptan-6-yl)nicotinamide	IC50	3.98 nM	US-10407409: 6-(5-hydroxy-1H-pyrazol-1-yl)nicotinamide inhibitors of PHD
6-(4-(4-cyano-2-methylphenyl)-5-hydroxy-1H-pyrazol-1-yl)-N-(2-(tetrahydrofuran-2-yl)ethyl)nicotinamide	IC50	3.98 nM	US-10407409: 6-(5-hydroxy-1H-pyrazol-1-yl)nicotinamide inhibitors of PHD
4-(1-(5-(3-(dimethylamino)azetidine-1-carbonyl)pyridin-2-yl)-5-hydroxy-1H-pyrazol-4-yl)-2-fluoro-3-methylbenzonitrile	IC50	3.98 nM	US-10407409: 6-(5-hydroxy-1H-pyrazol-1-yl)nicotinamide inhibitors of PHD
6-(4-(4-cyano-2-methylphenyl)-5-hydroxy-1H-pyrazol-1-yl)-N-methylnicotinamide	IC50	3.98 nM	US-10407409: 6-(5-hydroxy-1H-pyrazol-1-yl)nicotinamide inhibitors of PHD
(R)-4-(1-(5-(4-ethyl-3-methylpiperazine-1-carbonyl)pyridin-2-yl)-5-hydroxy-1H-pyrazol-4-yl)-2-fluoro-3-methylbenzonitrile	IC50	3.98 nM	US-10407409: 6-(5-hydroxy-1H-pyrazol-1-yl)nicotinamide inhibitors of PHD
6-(5-hydroxy-4-(2-methoxypyridin-4-yl)-1H-pyrazol-1-yl)-N-((1-(methoxymethyl)cyclopentyl)methyl)nicotinamide	IC50	3.98 nM	US-10407409: 6-(5-hydroxy-1H-pyrazol-1-yl)nicotinamide inhibitors of PHD
US10407409, Example 297	IC50	4.07 nM	US-10407409: 6-(5-hydroxy-1H-pyrazol-1-yl)nicotinamide inhibitors of PHD
4-(1-(5-(4-cyclopropylpiperazine-1-carbonyl)pyridin-2-yl)-5-hydroxy-1H-pyrazol-4-yl)-2-fluoro-3-methylbenzonitrile	IC50	4.07 nM	US-10407409: 6-(5-hydroxy-1H-pyrazol-1-yl)nicotinamide inhibitors of PHD
(S)-4-(1-(5-(4-ethyl-3-methylpiperazine-1-carbonyl)pyridin-2-yl)-5-hydroxy-1H-pyrazol-4-yl)-2-fluoro-3-methylbenzonitrile	IC50	4.07 nM	US-10407409: 6-(5-hydroxy-1H-pyrazol-1-yl)nicotinamide inhibitors of PHD
(R)-4-(1-(5-(3,4-dimethylpiperazine-1-carbonyl)pyridin-2-yl)-5-hydroxy-1H-pyrazol-4-yl)-2-fluoro-3-methylbenzonitrile	IC50	4.07 nM	US-10407409: 6-(5-hydroxy-1H-pyrazol-1-yl)nicotinamide inhibitors of PHD
4-(1-(5-(4-cyclopropylpiperazine-1-carbonyl)pyridin-2-yl)-5-hydroxy-1H-pyrazol-4-yl)-3-methylbenzonitrile	IC50	4.07 nM	US-10407409: 6-(5-hydroxy-1H-pyrazol-1-yl)nicotinamide inhibitors of PHD
2-(4-Hydroxy-2-oxo-1-(3’- (trifluoromethoxy)-[1,1’- biphenyl]-4-yl)-1,2,5,7- tetrahydrothieno[3,4-b] pyridine-3-arboxamido) acetic acid	IC50	4.1 nM	US-10208060: Inhibitors of HIF prolyl hydroxylase
(R)-2-fluoro-4-(5-hydroxy-1-(5-(4-isopropyl-3-methylpiperazine-1-carbonyl)pyridin-2-yl)-1H-pyrazol-4-yl)-3-methylbenzonitrile	IC50	4.37 nM	US-10407409: 6-(5-hydroxy-1H-pyrazol-1-yl)nicotinamide inhibitors of PHD
6-(4-(4-cyanophenyl)-5-hydroxy-1H-pyrazol-1-yl)-N-(1-(2-methoxy ethyl)cyclopentyl)nicotinamide	IC50	4.37 nM	US-10407409: 6-(5-hydroxy-1H-pyrazol-1-yl)nicotinamide inhibitors of PHD
(S)-4-(1-(5-(3-(dimethylamino)pyrrolidine-1-carbonyl)pyridin-2-yl)-5-hydroxy-1H-pyrazol-4-yl)-2-fluoro-3-methylbenzonitrile	IC50	4.47 nM	US-10407409: 6-(5-hydroxy-1H-pyrazol-1-yl)nicotinamide inhibitors of PHD
4-(1-(5-(3-(dimethylamino)azetidine-1-carbonyl)pyridin-2-yl)-5-hydroxy-1H-pyrazol-4-yl)-3-methylbenzonitrile	IC50	4.47 nM	US-10407409: 6-(5-hydroxy-1H-pyrazol-1-yl)nicotinamide inhibitors of PHD
(R)-4-(1-(5-(4-ethyl-2-methylpiperazine-1-carbonyl)pyridin-2-yl)-5-hydroxy-1H-pyrazol-4-yl)-2-fluoro-3-methylbenzonitrile	IC50	4.57 nM	US-10407409: 6-(5-hydroxy-1H-pyrazol-1-yl)nicotinamide inhibitors of PHD
4-(1-(5-(4-cyclopropyl-1,4-diazepane-1-carbonyl)pyridin-2-yl)-5-hydroxy-1H-pyrazol-4-yl)-2-fluoro-3-methylbenzonitrile	IC50	4.68 nM	US-10407409: 6-(5-hydroxy-1H-pyrazol-1-yl)nicotinamide inhibitors of PHD

ChEMBL bioactivities

2304 potent at pChembl≥5 of 2717 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.70	IC50	0.2	nM	CHEMBL2043325
9.70	IC50	0.2	nM	CHEMBL2041169
9.70	IC50	0.2	nM	CHEMBL2041175
9.70	IC50	0.2	nM	CHEMBL2041182
9.70	IC50	0.2	nM	CHEMBL2041184
9.70	IC50	0.2	nM	CHEMBL2041185
9.70	IC50	0.2	nM	CHEMBL2041186
9.70	IC50	0.2	nM	CHEMBL2041190
9.70	IC50	0.2	nM	CHEMBL2041192
9.70	IC50	0.2	nM	CHEMBL2041193
9.40	IC50	0.4	nM	CHEMBL2043010
9.40	IC50	0.4	nM	CHEMBL2043168
9.40	IC50	0.4	nM	CHEMBL2043169
9.40	IC50	0.4	nM	CHEMBL2043324
9.40	IC50	0.4	nM	CHEMBL2041188
9.40	IC50	0.4	nM	CHEMBL2041189
9.30	IC50	0.5	nM	CHEMBL2043326
9.30	IC50	0.5	nM	CHEMBL2041178
9.30	IC50	0.5	nM	CHEMBL2041183
9.30	IC50	0.5012	nM	CHEMBL2042853
9.22	IC50	0.6	nM	CHEMBL2041010
9.22	IC50	0.6	nM	CHEMBL2041170
9.22	IC50	0.6	nM	CHEMBL2040854
9.21	IC50	0.62	nM	CHEMBL4167582
9.19	IC50	0.65	nM	CHEMBL3115307
9.15	IC50	0.7	nM	CHEMBL2042993
9.15	IC50	0.7	nM	CHEMBL3115276
9.15	IC50	0.7	nM	CHEMBL3115311
9.15	IC50	0.7	nM	CHEMBL4171446
9.10	IC50	0.8	nM	CHEMBL2043171
9.10	IC50	0.8	nM	CHEMBL2041177
9.10	IC50	0.8	nM	CHEMBL2041187
9.10	IC50	0.8	nM	CHEMBL2041194
9.05	IC50	0.9	nM	CHEMBL2040897
9.05	IC50	0.9	nM	CHEMBL4161223
9.00	IC50	1	nM	CHEMBL2043172
9.00	IC50	1	nM	CHEMBL2041191
9.00	IC50	1	nM	CHEMBL2443222
9.00	IC50	1	nM	CHEMBL4170335
9.00	IC50	1	nM	CHEMBL4783524
9.00	IC50	1	nM	CHEMBL5572635
9.00	IC50	1	nM	CHEMBL5590779
8.96	IC50	1.1	nM	CHEMBL2043011
8.96	IC50	1.1	nM	CHEMBL2041171
8.96	IC50	1.1	nM	CHEMBL4785918
8.89	IC50	1.3	nM	CHEMBL4161223
8.89	IC50	1.3	nM	CHEMBL4796629
8.85	IC50	1.4	nM	CHEMBL4781541
8.82	IC50	1.5	nM	CHEMBL2041174
8.82	IC50	1.5	nM	CHEMBL3115302

PubChem BioAssay actives

663 with measured affinity, of 1301 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
3-[4-(1,3-benzothiazol-5-yl)phenyl]-8-[(3-methyl-2-pyridinyl)methyl]-1-(6-oxo-1H-pyrimidin-4-yl)-1,3,8-triazaspiro[4.5]decane-2,4-dione	666420: Inhibition of FLAG-tagged PHD2 expressed in baculovirus infected insect sf9 cells using biotinyl-DLDLEMLAPYIPMDDDFQL as substrate preincubated with compound for 30 mins measured after 2 hrs by time resolved fluorescence analysis	ic50	0.0002	uM
8-[(3-methyl-2-pyridinyl)methyl]-1-(6-oxo-1H-pyrimidin-4-yl)-3-[4-[4-(1H-pyrazol-5-yl)phenyl]phenyl]-1,3,8-triazaspiro[4.5]decane-2,4-dione	666420: Inhibition of FLAG-tagged PHD2 expressed in baculovirus infected insect sf9 cells using biotinyl-DLDLEMLAPYIPMDDDFQL as substrate preincubated with compound for 30 mins measured after 2 hrs by time resolved fluorescence analysis	ic50	0.0002	uM
3-methyl-4-[4-[8-[(3-methyl-2-pyridinyl)methyl]-2,4-dioxo-1-pyrimidin-4-yl-1,3,8-triazaspiro[4.5]decan-3-yl]phenyl]benzoic acid	1067674: Inhibition of FLAG-tagged full length PHD2 (unknown origin) expressed in Sf9 cells using HIF-1alpha peptide as substrate preincubated for 30 mins followed by substrate addition measured after 2 hrs by HTRF assay in presence of 2-oxoglutarate	ic50	0.0002	uM
3-methyl-4-[4-[8-[(3-methyl-2-pyridinyl)methyl]-1-(2-methylpyrimidin-4-yl)-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-3-yl]phenyl]benzoic acid	666420: Inhibition of FLAG-tagged PHD2 expressed in baculovirus infected insect sf9 cells using biotinyl-DLDLEMLAPYIPMDDDFQL as substrate preincubated with compound for 30 mins measured after 2 hrs by time resolved fluorescence analysis	ic50	0.0002	uM
4-[4-[1-(6-methoxypyrimidin-4-yl)-8-[(3-methyl-2-pyridinyl)methyl]-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-3-yl]phenyl]-3-methylbenzoic acid	666420: Inhibition of FLAG-tagged PHD2 expressed in baculovirus infected insect sf9 cells using biotinyl-DLDLEMLAPYIPMDDDFQL as substrate preincubated with compound for 30 mins measured after 2 hrs by time resolved fluorescence analysis	ic50	0.0002	uM
4-[4-[8-[(3-methyl-2-pyridinyl)methyl]-2,4-dioxo-1-pyrimidin-4-yl-1,3,8-triazaspiro[4.5]decan-3-yl]phenyl]benzoic acid	666420: Inhibition of FLAG-tagged PHD2 expressed in baculovirus infected insect sf9 cells using biotinyl-DLDLEMLAPYIPMDDDFQL as substrate preincubated with compound for 30 mins measured after 2 hrs by time resolved fluorescence analysis	ic50	0.0002	uM
3-methyl-4-[4-[8-[(3-methyl-2-pyridinyl)methyl]-2,4-dioxo-1-pyrazin-2-yl-1,3,8-triazaspiro[4.5]decan-3-yl]phenyl]benzoic acid	666420: Inhibition of FLAG-tagged PHD2 expressed in baculovirus infected insect sf9 cells using biotinyl-DLDLEMLAPYIPMDDDFQL as substrate preincubated with compound for 30 mins measured after 2 hrs by time resolved fluorescence analysis	ic50	0.0002	uM
3-methyl-4-[4-[8-[(3-methyl-2-pyridinyl)methyl]-1-(6-methylpyrimidin-4-yl)-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-3-yl]phenyl]benzoic acid	666420: Inhibition of FLAG-tagged PHD2 expressed in baculovirus infected insect sf9 cells using biotinyl-DLDLEMLAPYIPMDDDFQL as substrate preincubated with compound for 30 mins measured after 2 hrs by time resolved fluorescence analysis	ic50	0.0002	uM
4-[4-[1-(3-methoxypyrazin-2-yl)-8-[(3-methyl-2-pyridinyl)methyl]-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-3-yl]phenyl]-3-methylbenzoic acid	666420: Inhibition of FLAG-tagged PHD2 expressed in baculovirus infected insect sf9 cells using biotinyl-DLDLEMLAPYIPMDDDFQL as substrate preincubated with compound for 30 mins measured after 2 hrs by time resolved fluorescence analysis	ic50	0.0002	uM
3-methyl-4-[4-[1-(3-methylpyrazin-2-yl)-8-[(3-methyl-2-pyridinyl)methyl]-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-3-yl]phenyl]benzoic acid	666420: Inhibition of FLAG-tagged PHD2 expressed in baculovirus infected insect sf9 cells using biotinyl-DLDLEMLAPYIPMDDDFQL as substrate preincubated with compound for 30 mins measured after 2 hrs by time resolved fluorescence analysis	ic50	0.0002	uM
4-[4-[1-(6-methoxypyrimidin-4-yl)-8-[(3-methyl-2-pyridinyl)methyl]-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-3-yl]phenyl]benzoic acid	666420: Inhibition of FLAG-tagged PHD2 expressed in baculovirus infected insect sf9 cells using biotinyl-DLDLEMLAPYIPMDDDFQL as substrate preincubated with compound for 30 mins measured after 2 hrs by time resolved fluorescence analysis	ic50	0.0004	uM
3-fluoro-4-[4-[1-(6-methoxypyrimidin-4-yl)-8-[(3-methyl-2-pyridinyl)methyl]-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-3-yl]phenyl]benzoic acid	666420: Inhibition of FLAG-tagged PHD2 expressed in baculovirus infected insect sf9 cells using biotinyl-DLDLEMLAPYIPMDDDFQL as substrate preincubated with compound for 30 mins measured after 2 hrs by time resolved fluorescence analysis	ic50	0.0004	uM
1-(6-methoxypyrimidin-4-yl)-8-[(3-methyl-2-pyridinyl)methyl]-2,4-dioxo-3-(4-phenylphenyl)-1,3,8-triazaspiro[4.5]decane-6-carboxylic acid	666420: Inhibition of FLAG-tagged PHD2 expressed in baculovirus infected insect sf9 cells using biotinyl-DLDLEMLAPYIPMDDDFQL as substrate preincubated with compound for 30 mins measured after 2 hrs by time resolved fluorescence analysis	ic50	0.0004	uM
3-[4-[1-(6-methoxypyrimidin-4-yl)-8-[(3-methyl-2-pyridinyl)methyl]-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-3-yl]phenyl]benzoic acid	666420: Inhibition of FLAG-tagged PHD2 expressed in baculovirus infected insect sf9 cells using biotinyl-DLDLEMLAPYIPMDDDFQL as substrate preincubated with compound for 30 mins measured after 2 hrs by time resolved fluorescence analysis	ic50	0.0004	uM
3-methyl-4-[4-[8-[(3-methyl-2-pyridinyl)methyl]-2,4-dioxo-1-pyrimidin-2-yl-1,3,8-triazaspiro[4.5]decan-3-yl]phenyl]benzoic acid	666420: Inhibition of FLAG-tagged PHD2 expressed in baculovirus infected insect sf9 cells using biotinyl-DLDLEMLAPYIPMDDDFQL as substrate preincubated with compound for 30 mins measured after 2 hrs by time resolved fluorescence analysis	ic50	0.0004	uM
4-[4-[8-[(3-methyl-2-pyridinyl)methyl]-2,4-dioxo-1-pyrazin-2-yl-1,3,8-triazaspiro[4.5]decan-3-yl]phenyl]benzoic acid	666420: Inhibition of FLAG-tagged PHD2 expressed in baculovirus infected insect sf9 cells using biotinyl-DLDLEMLAPYIPMDDDFQL as substrate preincubated with compound for 30 mins measured after 2 hrs by time resolved fluorescence analysis	ic50	0.0004	uM
4-[4-[1-(6-methoxypyrimidin-4-yl)-8-[(3-methyl-2-pyridinyl)methyl]-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-3-yl]phenyl]-2-methylbenzoic acid	666420: Inhibition of FLAG-tagged PHD2 expressed in baculovirus infected insect sf9 cells using biotinyl-DLDLEMLAPYIPMDDDFQL as substrate preincubated with compound for 30 mins measured after 2 hrs by time resolved fluorescence analysis	ic50	0.0005	uM
3-methyl-4-[4-[8-[(3-methyl-2-pyridinyl)methyl]-2,4-dioxo-1-[6-(trifluoromethyl)pyrimidin-4-yl]-1,3,8-triazaspiro[4.5]decan-3-yl]phenyl]benzoic acid	666420: Inhibition of FLAG-tagged PHD2 expressed in baculovirus infected insect sf9 cells using biotinyl-DLDLEMLAPYIPMDDDFQL as substrate preincubated with compound for 30 mins measured after 2 hrs by time resolved fluorescence analysis	ic50	0.0005	uM
4-[4-[1-(6-methoxypyrimidin-4-yl)-8-[(3-methyl-2-pyridinyl)methyl]-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-3-yl]phenyl]-N-methylbenzamide	666420: Inhibition of FLAG-tagged PHD2 expressed in baculovirus infected insect sf9 cells using biotinyl-DLDLEMLAPYIPMDDDFQL as substrate preincubated with compound for 30 mins measured after 2 hrs by time resolved fluorescence analysis	ic50	0.0005	uM
1’-[(3-methyl-2-pyridinyl)methyl]-1-(4-phenylphenyl)spiro[indole-3,4’-piperidine]-2-one	779535: Inhibition of PHD2 (unknown origin) by HTRF assay	ic50	0.0005	uM
3-[[5-(benzhydrylcarbamoyl)-4-oxo-1H-pyridine-2-carbonyl]amino]propanoic acid	1354497: Inhibition of FLAG- tagged full length HIF-PHD2 (unknown origin) expressed in baculovirus-infected Sf9 cells using biotin labelled DLDLEMLAPYIPMDDDFQL as substrate preincubated for 5 mins followed by substrate addition measured after 45 mins by LANCE assay	ic50	0.0006	uM
3-methyl-4-[5-[8-[(3-methyl-2-pyridinyl)methyl]-2,4-dioxo-1-(6-oxo-1H-pyrimidin-4-yl)-1,3,8-triazaspiro[4.5]decan-3-yl]-2-pyridinyl]benzoic acid	666420: Inhibition of FLAG-tagged PHD2 expressed in baculovirus infected insect sf9 cells using biotinyl-DLDLEMLAPYIPMDDDFQL as substrate preincubated with compound for 30 mins measured after 2 hrs by time resolved fluorescence analysis	ic50	0.0006	uM
8-[(3-methyl-2-pyridinyl)methyl]-3-[4-(4-morpholin-4-ylphenyl)phenyl]-1-(6-oxo-1H-pyrimidin-4-yl)-1,3,8-triazaspiro[4.5]decane-2,4-dione	666420: Inhibition of FLAG-tagged PHD2 expressed in baculovirus infected insect sf9 cells using biotinyl-DLDLEMLAPYIPMDDDFQL as substrate preincubated with compound for 30 mins measured after 2 hrs by time resolved fluorescence analysis	ic50	0.0006	uM
2-[[6-chloro-4-hydroxy-2-oxo-1-[[6-(trifluoromethyl)-3-pyridinyl]methyl]-1,8-naphthyridine-3-carbonyl]amino]acetic acid	1067674: Inhibition of FLAG-tagged full length PHD2 (unknown origin) expressed in Sf9 cells using HIF-1alpha peptide as substrate preincubated for 30 mins followed by substrate addition measured after 2 hrs by HTRF assay in presence of 2-oxoglutarate	ic50	0.0006	uM
5-[4-[1-(6-methoxypyrimidin-4-yl)-8-[(3-methyl-2-pyridinyl)methyl]-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-3-yl]phenyl]thiophene-2-carboxylic acid	666420: Inhibition of FLAG-tagged PHD2 expressed in baculovirus infected insect sf9 cells using biotinyl-DLDLEMLAPYIPMDDDFQL as substrate preincubated with compound for 30 mins measured after 2 hrs by time resolved fluorescence analysis	ic50	0.0006	uM
2-naphthalen-2-yl-N-(6-oxo-2-pyrazol-1-yl-1H-pyrimidin-5-yl)acetamide	1067674: Inhibition of FLAG-tagged full length PHD2 (unknown origin) expressed in Sf9 cells using HIF-1alpha peptide as substrate preincubated for 30 mins followed by substrate addition measured after 2 hrs by HTRF assay in presence of 2-oxoglutarate	ic50	0.0007	uM
N-(6-oxo-2-pyrazol-1-yl-1H-pyrimidin-5-yl)-2-(4-phenylphenyl)acetamide	1354496: Inhibition of FLAG- tagged full length HIF-PHD2 (unknown origin) expressed in baculovirus-infected Sf9 cells using biotin labelled DLDLEMLAPYIPMDDDFQL as substrate preincubated for 30 mins followed by substrate addition measured after 2 hrs by LANCE assay	ic50	0.0007	uM
1’-[(3-methyl-2-pyridinyl)methyl]-2-oxo-1-(4-phenylphenyl)spiro[indole-3,4’-piperidine]-5-carboxylic acid	666420: Inhibition of FLAG-tagged PHD2 expressed in baculovirus infected insect sf9 cells using biotinyl-DLDLEMLAPYIPMDDDFQL as substrate preincubated with compound for 30 mins measured after 2 hrs by time resolved fluorescence analysis	ic50	0.0007	uM
1’-[(6-methyl-2-pyridinyl)methyl]-2-oxo-1-(4-phenylphenyl)spiro[indole-3,4’-piperidine]-5-carboxylic acid	1067674: Inhibition of FLAG-tagged full length PHD2 (unknown origin) expressed in Sf9 cells using HIF-1alpha peptide as substrate preincubated for 30 mins followed by substrate addition measured after 2 hrs by HTRF assay in presence of 2-oxoglutarate	ic50	0.0007	uM
4-[4-[8-[(3-methyl-2-pyridinyl)methyl]-2,4-dioxo-1-pyrimidin-2-yl-1,3,8-triazaspiro[4.5]decan-3-yl]phenyl]benzoic acid	666420: Inhibition of FLAG-tagged PHD2 expressed in baculovirus infected insect sf9 cells using biotinyl-DLDLEMLAPYIPMDDDFQL as substrate preincubated with compound for 30 mins measured after 2 hrs by time resolved fluorescence analysis	ic50	0.0008	uM
4-[4-[1-(6-methoxypyrimidin-4-yl)-8-[(3-methyl-2-pyridinyl)methyl]-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-3-yl]phenyl]benzamide	666420: Inhibition of FLAG-tagged PHD2 expressed in baculovirus infected insect sf9 cells using biotinyl-DLDLEMLAPYIPMDDDFQL as substrate preincubated with compound for 30 mins measured after 2 hrs by time resolved fluorescence analysis	ic50	0.0008	uM
3-chloro-4-[4-[1-(6-methoxypyrimidin-4-yl)-8-[(3-methyl-2-pyridinyl)methyl]-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-3-yl]phenyl]benzoic acid	666420: Inhibition of FLAG-tagged PHD2 expressed in baculovirus infected insect sf9 cells using biotinyl-DLDLEMLAPYIPMDDDFQL as substrate preincubated with compound for 30 mins measured after 2 hrs by time resolved fluorescence analysis	ic50	0.0008	uM
3-methyl-4-[5-[8-[(3-methyl-2-pyridinyl)methyl]-2,4-dioxo-1-pyrimidin-4-yl-1,3,8-triazaspiro[4.5]decan-3-yl]-2-pyridinyl]benzoic acid	666420: Inhibition of FLAG-tagged PHD2 expressed in baculovirus infected insect sf9 cells using biotinyl-DLDLEMLAPYIPMDDDFQL as substrate preincubated with compound for 30 mins measured after 2 hrs by time resolved fluorescence analysis	ic50	0.0008	uM
2-[[7-cyano-10-hydroxy-12-oxo-3-[4-(trifluoromethyl)phenyl]-4-oxa-1-azatricyclo[7.3.1.05,13]trideca-5,7,9(13),10-tetraene-11-carbonyl]amino]acetic acid	1354497: Inhibition of FLAG- tagged full length HIF-PHD2 (unknown origin) expressed in baculovirus-infected Sf9 cells using biotin labelled DLDLEMLAPYIPMDDDFQL as substrate preincubated for 5 mins followed by substrate addition measured after 45 mins by LANCE assay	ic50	0.0009	uM
3-[4-(2,4-dimethyl-1,3-thiazol-5-yl)phenyl]-8-[(3-methyl-2-pyridinyl)methyl]-1-(6-oxo-1H-pyrimidin-4-yl)-1,3,8-triazaspiro[4.5]decane-2,4-dione	666420: Inhibition of FLAG-tagged PHD2 expressed in baculovirus infected insect sf9 cells using biotinyl-DLDLEMLAPYIPMDDDFQL as substrate preincubated with compound for 30 mins measured after 2 hrs by time resolved fluorescence analysis	ic50	0.0009	uM
2-[[7-cyano-10-hydroxy-12-oxo-3-[4-(trifluoromethyl)phenyl]-1,4-diazatricyclo[7.3.1.05,13]trideca-5,7,9(13),10-tetraene-11-carbonyl]amino]acetic acid	1354497: Inhibition of FLAG- tagged full length HIF-PHD2 (unknown origin) expressed in baculovirus-infected Sf9 cells using biotin labelled DLDLEMLAPYIPMDDDFQL as substrate preincubated for 5 mins followed by substrate addition measured after 45 mins by LANCE assay	ic50	0.0010	uM
N-[(6-cyano-3-pyridinyl)methyl]-5-hydroxy-2-(6-hydroxy-2-azaspiro[3.3]heptan-2-yl)-1,7-naphthyridine-6-carboxamide	2098227: Inhibition of PHD2 (unknown origin) preincubated for 30 mins followed by substrate addition and measured after 30 mins by HTS plate reader analysis	ic50	0.0010	uM
N-[(6-cyano-3-pyridinyl)methyl]-5-hydroxy-2-[methyl(oxan-4-yl)amino]-1,7-naphthyridine-6-carboxamide	2098227: Inhibition of PHD2 (unknown origin) preincubated for 30 mins followed by substrate addition and measured after 30 mins by HTS plate reader analysis	ic50	0.0010	uM
N-[bis(4-methoxyphenyl)methyl]-6-oxo-2-pyridazin-3-yl-1H-pyrimidine-5-carboxamide	1735022: Inhibition of FLAG-tagged full-length HIF-PHD2 (unknown origin) expressed in baculovirus infected Sf9 cells using 2-oxoglutarate and HIF1alpha biotinyl-DLDLEMLAPYIPMDDDFQL as peptide substrates preincubated for 30 mins followed by substrate addition and measured after 2 hrs by LANCE assay	ic50	0.0010	uM
2-chloro-4-[4-[1-(6-methoxypyrimidin-4-yl)-8-[(3-methyl-2-pyridinyl)methyl]-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-3-yl]phenyl]benzoic acid	666420: Inhibition of FLAG-tagged PHD2 expressed in baculovirus infected insect sf9 cells using biotinyl-DLDLEMLAPYIPMDDDFQL as substrate preincubated with compound for 30 mins measured after 2 hrs by time resolved fluorescence analysis	ic50	0.0010	uM
3-methyl-4-[5-[8-[(3-methyl-2-pyridinyl)methyl]-2,4-dioxo-1-pyrazin-2-yl-1,3,8-triazaspiro[4.5]decan-3-yl]-2-pyridinyl]benzoic acid	666420: Inhibition of FLAG-tagged PHD2 expressed in baculovirus infected insect sf9 cells using biotinyl-DLDLEMLAPYIPMDDDFQL as substrate preincubated with compound for 30 mins measured after 2 hrs by time resolved fluorescence analysis	ic50	0.0010	uM
3-[5-methyl-6-[[1-oxo-2-(4-phenylphenyl)-2,8-diazaspiro[4.5]decan-8-yl]methyl]-3-pyridinyl]propanoic acid	779535: Inhibition of PHD2 (unknown origin) by HTRF assay	ic50	0.0010	uM
4-[4-[8-[(3-methyl-2-pyridinyl)methyl]-2,4-dioxo-1-(6-oxo-1H-pyrimidin-4-yl)-1,3,8-triazaspiro[4.5]decan-3-yl]phenyl]benzoic acid	666420: Inhibition of FLAG-tagged PHD2 expressed in baculovirus infected insect sf9 cells using biotinyl-DLDLEMLAPYIPMDDDFQL as substrate preincubated with compound for 30 mins measured after 2 hrs by time resolved fluorescence analysis	ic50	0.0011	uM
N-[bis(4-methoxyphenyl)methyl]-6-oxo-2-pyrazol-1-yl-1H-pyrimidine-5-carboxamide	1735022: Inhibition of FLAG-tagged full-length HIF-PHD2 (unknown origin) expressed in baculovirus infected Sf9 cells using 2-oxoglutarate and HIF1alpha biotinyl-DLDLEMLAPYIPMDDDFQL as peptide substrates preincubated for 30 mins followed by substrate addition and measured after 2 hrs by LANCE assay	ic50	0.0011	uM
1-(6-methoxypyrimidin-4-yl)-8-[(3-methyl-2-pyridinyl)methyl]-3-[4-[4-(5-oxo-1,2-dihydropyrazol-3-yl)phenyl]phenyl]-1,3,8-triazaspiro[4.5]decane-2,4-dione	666420: Inhibition of FLAG-tagged PHD2 expressed in baculovirus infected insect sf9 cells using biotinyl-DLDLEMLAPYIPMDDDFQL as substrate preincubated with compound for 30 mins measured after 2 hrs by time resolved fluorescence analysis	ic50	0.0011	uM
6-oxo-N-[(4-phenylphenyl)methyl]-2-pyrazol-1-yl-1H-pyrimidine-5-carboxamide	1735022: Inhibition of FLAG-tagged full-length HIF-PHD2 (unknown origin) expressed in baculovirus infected Sf9 cells using 2-oxoglutarate and HIF1alpha biotinyl-DLDLEMLAPYIPMDDDFQL as peptide substrates preincubated for 30 mins followed by substrate addition and measured after 2 hrs by LANCE assay	ic50	0.0013	uM
N-[(1S)-1-(4-methoxyphenyl)ethyl]-6-oxo-2-pyrazol-1-yl-1H-pyrimidine-5-carboxamide	1735022: Inhibition of FLAG-tagged full-length HIF-PHD2 (unknown origin) expressed in baculovirus infected Sf9 cells using 2-oxoglutarate and HIF1alpha biotinyl-DLDLEMLAPYIPMDDDFQL as peptide substrates preincubated for 30 mins followed by substrate addition and measured after 2 hrs by LANCE assay	ic50	0.0014	uM
2-[[7-cyano-10-hydroxy-12-oxo-3-[4-(trifluoromethyl)phenyl]-4-thia-1-azatricyclo[7.3.1.05,13]trideca-5,7,9(13),10-tetraene-11-carbonyl]amino]acetic acid	1354497: Inhibition of FLAG- tagged full length HIF-PHD2 (unknown origin) expressed in baculovirus-infected Sf9 cells using biotin labelled DLDLEMLAPYIPMDDDFQL as substrate preincubated for 5 mins followed by substrate addition measured after 45 mins by LANCE assay	ic50	0.0015	uM
2-[[2-(2-fluorophenyl)-5-hydroxy-8-methyl-7-oxopyrido[2,3-d]pyrimidine-6-carbonyl]amino]acetic acid	1067678: Inhibition of PHD2 (unknown origin) using P564 HIFlalpha as substrate after 1 hr by TR-FRET assay	ic50	0.0015	uM
3-[4-(3H-benzimidazol-5-yl)phenyl]-1-(6-methoxypyrimidin-4-yl)-8-[(3-methyl-2-pyridinyl)methyl]-1,3,8-triazaspiro[4.5]decane-2,4-dione	666420: Inhibition of FLAG-tagged PHD2 expressed in baculovirus infected insect sf9 cells using biotinyl-DLDLEMLAPYIPMDDDFQL as substrate preincubated with compound for 30 mins measured after 2 hrs by time resolved fluorescence analysis	ic50	0.0015	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Oxygen	increases reaction, affects cotreatment, decreases reaction, decreases activity, increases stability (+3 more)	7
cobaltous chloride	decreases reaction, decreases expression, increases expression	4
Tobacco Smoke Pollution	increases expression, affects expression	4
Valproic Acid	affects expression, decreases expression	3
zinc chloride	decreases reaction, increases expression, increases activity	2
nickel chloride	decreases activity, increases expression	2
andrographolide	decreases reaction, increases expression, decreases expression	2
N,N,N’,N’-tetrakis(2-pyridylmethyl)ethylenediamine	increases activity, decreases reaction	2
Tretinoin	increases expression	2
Zinc	decreases reaction, increases activity, decreases expression	2
aristolochic acid I	decreases expression	1
1-cyclopropyl-4-(4-((5-methyl-3-(3-(4-(trifluoromethoxy)phenyl)-1,2,4-oxadiazol-5-yl)-1H-pyrazol-1-yl)methyl)pyridin-2-yl)piperazine	decreases expression, increases reaction	1
GSK-J4	increases expression	1
FR900359	affects phosphorylation	1
dicrotophos	decreases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
alpha-naphthoflavone	affects cotreatment, decreases expression, decreases reaction, increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
ferrous sulfate	increases activity	1
1,10-phenanthroline	increases expression	1
cobalt sulfate	increases expression	1
myricetin	decreases expression, increases activity	1
3,3’,4,5’-tetrahydroxystilbene	decreases expression, increases activity	1
testosterone-3-carboxymethyloxime-bovine serum albumin conjugate	affects expression	1
dinophysistoxin 1	increases expression	1
CGP 52608	affects binding, increases reaction	1
entinostat	decreases expression	1
azaspiracid	increases expression	1
motexafin gadolinium	affects cotreatment, increases expression	1

ChEMBL screening assays

211 unique, capped per target: 211 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4411721	Binding	Inhibition of PHD (unknown origin) expressed in mouse NIH/3T3 cells harboring HRE-driven luciferase gene assessed as transactivation of HIF1alpha after 6 hrs by luciferase reporter gene assay	Triterpenoid Hydroxamates as HIF Prolyl Hydrolase Inhibitors. — J Nat Prod

Cellosaurus cell lines

5 cell lines: 4 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B7X2	Abcam Raji EGLN1 KO	Cancer cell line	Male
CVCL_B9XN	Abcam THP-1 EGLN1 KO	Cancer cell line	Male
CVCL_C6ZI	Abcam PC-3 EGLN1 KO	Cancer cell line	Male
CVCL_D9E1	Ubigene HEK293 EGLN1 KO	Transformed cell line	Female
CVCL_SL51	HAP1 EGLN1 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

301 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00365508	PHASE4	COMPLETED	Counseling and Nicotine Replacement Therapy in Helping Adult Smokers Quit Smoking
NCT00558155	PHASE4	COMPLETED	The Impact of Immunostimulating Nutrition on the Outcome of Surgery
NCT00576940	PHASE4	COMPLETED	Standard and Immunostimulating Enteral Nutrition in Surgical Patients
NCT00666978	PHASE4	COMPLETED	Health Education Counseling With or Without Bupropion in Helping African Americans Stop Smoking
NCT01038154	PHASE4	UNKNOWN	Study to Evaluate the Efficacy of Pravastatin on Survival and Recurrence of Advanced Gastroesophageal Cancer
NCT01234272	PHASE4	COMPLETED	Comparison of the Analgesic Effect Between Intrathecal Morphine and IV-fentanyl Patient Controlled Analgesia (ITM-IVPCA) and Epidural PCA (PCEA) in Patients Undergoing Gastrectomy -Randomized Allocation Study-
NCT01260194	PHASE4	TERMINATED	A Study of Herceptin (Trastuzumab) in Combination With Standard Chemotherapy in Patients With HER Positive Metastatic Gastric Cancer
NCT01271582	PHASE4	UNKNOWN	Investigation of Association Between UGT1A1 Polymorphisms and Irinotecan Toxicity in Korean Patients
NCT01401075	PHASE4	COMPLETED	RCT With Adjuvant Mistletoe Treatment in Gastric Cancer Patients
NCT01471756	PHASE4	COMPLETED	Improving Complete Endoscopic Mucosal Resection (EMR) of Colorectal Neoplasia
NCT01766765	PHASE4	UNKNOWN	Early Jejunostomy Nutrition Minimizes Time to Chemotherapy
NCT01910948	PHASE4	UNKNOWN	Perioperative Application of Omega-3 Polyunsaturated Fatty Acids in Gastric Cancer Patients
NCT01927328	PHASE4	UNKNOWN	Iron Replacement in Oesophagogastric Neoplasia
NCT01962272	PHASE4	COMPLETED	The Effect of Nutritional Counseling for Cancer Patients
NCT01962376	PHASE4	UNKNOWN	Preoperative Chemotherapy With Bevacizumab For Potentially Resectable Gastric Cancer With Liver Metastasis
NCT02047994	PHASE4	RECRUITING	Multicentric Randomized Study of H. Pylori Eradication and Pepsinogen Testing for Prevention of Gastric Cancer Mortality
NCT02235246	PHASE4	COMPLETED	The Effect of Perioperative Intravenous Magnesium on Pain After Endoscopic Submucosal Dissection for Gastric Neoplasm: Prospective Randomized Double-blind Placebo Controlled Study
NCT02366819	PHASE4	SUSPENDED	Genetic Analysis-Guided Irinotecan Hydrochloride Dosing of mFOLFIRINOX in Treating Patients With Locally Advanced Gastroesophageal or Stomach Cancer
NCT02401971	PHASE4	UNKNOWN	Irinotecan Plus Thalidomide in Second Line Advanced Gastric Cancer
NCT02458573	PHASE4	COMPLETED	Comparison of the Effects of Continuous Epidural Analgesia and Continuous Intravenous Analgesia on Postoperative Bowel Movement in Patients Undergoing Laparoscopic Gastrectomy
NCT02638584	PHASE4	COMPLETED	Effects of Ilaprazole on Ulcer Healing Rate and Prevention of Gastrointestinal Bleeding in the Patients Undergone ESD.
NCT02776527	PHASE4	UNKNOWN	A Clinical Trial of Maintenance Treatment of Apatinib in Advanced Gastric Cancer Patients Have Completed Postoprative Adjuvant Chemotherapy
NCT03384511	PHASE4	COMPLETED	The Use of 18F-ALF-NOTA-PRGD2 PET/CT Scan to Predict the Efficacy and Adverse Events of Apatinib in Malignancies.
NCT03550482	PHASE4	COMPLETED	Oncoxin® and Quality of Life in Cancer Patients
NCT03609892	PHASE4	COMPLETED	Helicobacter Rescue Therapy With Berberine Plus Amoxicillin Quadruple Therapy Versus Tetracycline Plus Furazolidone Quadruple Therapy
NCT03642093	PHASE4	UNKNOWN	HOPE - A Study to Evaluate the Effect of a Prehabilitation Program on GI Cancer Patients Planning to Undergo Surgery
NCT03733639	PHASE4	UNKNOWN	Tisseel® as a Reinforcement of Esophagojejunal Anastomoses
NCT04168346	PHASE4	NOT_YET_RECRUITING	Preoperative Intravenous Iron Therapy in Patients With Gastric Cancer
NCT04209933	PHASE4	COMPLETED	Helicobacter Pylori Eradication With Different Bismuth Quadruple Therapies
NCT04591028	PHASE4	WITHDRAWN	A Study to Evaluate Indocyanine Green Lymphangiography to Improve Lymphadenectomy in Gastric Cancer Patients
NCT04607057	PHASE4	UNKNOWN	Supplemental Parenteral Nutrition During Postgastrectomy in Nutritionally at Risk Patient
NCT04660123	PHASE4	COMPLETED	A Real World Study of Bismuth Colloidal Pectin Granules Quadruple Therapy for H. Pylori Eradication
NCT04678492	PHASE4	COMPLETED	Helicobacter Rescue Therapy With High-dose Esomeprazole and Amoxicillin Dual Therapy Versus Bismuth-containing Quadruple Therapy
NCT04697186	PHASE4	COMPLETED	Helicobacter Pylori Eradication With Berberine Plus Amoxicillin Triple Therapy Versus Bismuth-containing Quadruple Therapy
NCT05029453	PHASE4	UNKNOWN	Apatinib Combined With Chemotherapy Versus Chemotherapy in Second-line Gastric Cancer Receiving Prior Anti-PD-1 Therapy
NCT05183126	PHASE4	RECRUITING	Pharmacokinetic Study of Skeletal Muscle Area-based Paclitaxel Infusion in Patients With Cancer
NCT05354856	PHASE4	TERMINATED	The Effect of Chemoradiotherapy on Gastric Perfusion in Patients With Gastric Cancer.
NCT05410535	PHASE4	COMPLETED	To Evaluate Efficacy of Ursodeoxycholic Acid (UDCA) for the Prevention of Gallstone Formation After Gasterectomy
NCT05498766	PHASE4	NOT_YET_RECRUITING	Effect and Safety of Huaier Granule Versus SOX Regimen in Gastric Cancer Patients
NCT05518929	PHASE4	COMPLETED	Hypoxia During Gastroenterological Endoscope Procedures Sedated With Ciprofol In Overweight Or Obesity Patients