NOS2
gene geneOn this page
Also known as iNOSNOSHEP-NOS
Summary
NOS2 (nitric oxide synthase 2, HGNC:7873) is a protein-coding gene on chromosome 17q11.2, encoding Nitric oxide synthase, inducible (P35228). Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body.
Nitric oxide is a reactive free radical which acts as a biologic mediator in several processes, including neurotransmission and antimicrobial and antitumoral activities. This gene encodes a nitric oxide synthase which is expressed in liver and is inducible by a combination of lipopolysaccharide and certain cytokines. Three related pseudogenes are located within the Smith-Magenis syndrome region on chromosome 17.
Source: NCBI Gene 4843 — RefSeq curated summary.
At a glance
- Gene–disease (curated): schizophrenia (No Known Disease Relationship, GenCC)
- Clinical variants (ClinVar): 213 total
- GTEx eGene: eQTL in 43 tissues, sQTL in 3 (q < 0.05)
- Drug target: yes — 2 curated mechanism-of-action drugs, 1 via a complex or family; 10 molecules with ChEMBL bioactivity (top 3% of genes corpus-wide)
- Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.86 (unconstrained)
- MANE Select transcript:
NM_000625 - Interaction hub: 2,454 STRING partners (top 4% of genes corpus-wide)
- Notable: 213 clinical variants but no curated precision-oncology (CIViC) evidence yet
Identifiers
Gene identifiers
| Field | Value |
|---|---|
| HGNC ID | HGNC:7873 |
| Approved symbol | NOS2 |
| Name | nitric oxide synthase 2 |
| Location | 17q11.2 |
| Locus type | gene with protein product |
| Status | Approved |
| Aliases | iNOS, NOS, HEP-NOS |
| Ensembl gene | ENSG00000007171 |
| Ensembl biotype | protein_coding |
| OMIM | 163730 |
| Entrez | 4843 |
Gene structure
Transcript identifiers
Ensembl transcripts: 9 — 5 protein_coding, 3 nonsense_mediated_decay, 1 retained_intron
MANE Select: ENST00000313735
Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1
ENST00000313735, ENST00000646938, ENST00000697337, ENST00000697338, ENST00000697339, ENST00000697340, ENST00000697341, ENST00000886820, ENST00001139812
RefSeq mRNA: 1 — MANE Select: NM_000625
NM_000625
CCDS: CCDS11223
Canonical transcript exons
ENST00000313735 — 27 exons
| Exon | Start | End |
|---|---|---|
| ENSE00000406697 | 27769535 | 27769584 |
| ENSE00000704507 | 27773161 | 27773243 |
| ENSE00000704841 | 27778690 | 27778791 |
| ENSE00000705157 | 27782015 | 27782106 |
| ENSE00000946394 | 27770913 | 27771017 |
| ENSE00001126885 | 27765535 | 27765716 |
| ENSE00001126938 | 27778882 | 27779056 |
| ENSE00001126954 | 27781036 | 27781177 |
| ENSE00001251604 | 27763981 | 27764144 |
| ENSE00001251789 | 27780767 | 27780906 |
| ENSE00001292830 | 27762798 | 27763005 |
| ENSE00001302992 | 27798700 | 27798882 |
| ENSE00001304187 | 27761144 | 27761231 |
| ENSE00001309781 | 27768977 | 27769151 |
| ENSE00001310933 | 27766510 | 27766588 |
| ENSE00001310953 | 27788809 | 27788931 |
| ENSE00001312003 | 27774257 | 27774451 |
| ENSE00001312300 | 27782944 | 27783106 |
| ENSE00001322003 | 27758881 | 27759075 |
| ENSE00001327291 | 27789604 | 27789688 |
| ENSE00001327457 | 27772308 | 27772452 |
| ENSE00001347743 | 27767705 | 27767837 |
| ENSE00001347946 | 27787678 | 27787826 |
| ENSE00001704085 | 27756766 | 27757353 |
| ENSE00001842263 | 27800339 | 27800529 |
| ENSE00002334691 | 27760030 | 27760178 |
| ENSE00002411104 | 27760623 | 27760744 |
Expression profiles
Bgee: expression breadth ubiquitous, 153 present calls, max score 94.55.
FANTOM5 (CAGE): breadth broad, TPM avg 8.9028 / max 1337.0827, expressed in 242 samples.
Highest expression (Bgee): cartilage tissue, olfactory segment of nasal mucosa, mucosa of paranasal sinus, mucosa of transverse colon, rectum.
Genetic regulation across tissues (GTEx eQTL / sQTL)
NOS2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 43 tissues and its splicing (sQTL) in 3 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.
showing 20 of 46 significant tissue × QTL associations:
| Tissue | QTL | q-value | Slope | Lead variant |
|---|---|---|---|---|
| Nerve Tibial | eqtl | 7.7e-167 | -1.07 | 17:27879388:C:A |
| Skin Sun Exposed Lower leg | eqtl | 2.0e-125 | -1.09 | 17:27879388:C:A |
| Skin Not Sun Exposed Suprapubic | eqtl | 1.9e-84 | -1.04 | 17:27879388:C:A |
| Artery Tibial | eqtl | 2.7e-79 | -0.87 | 17:27879388:C:A |
| Esophagus Muscularis | eqtl | 8.2e-79 | -1.01 | 17:27879388:C:A |
| Adipose Subcutaneous | eqtl | 1.4e-72 | -0.82 | 17:27879388:C:A |
| Esophagus Gastroesophageal Junction | eqtl | 6.0e-67 | -0.99 | 17:27879388:C:A |
| Muscle Skeletal | eqtl | 4.6e-59 | -0.72 | 17:27879388:C:A |
| Brain Nucleus accumbens basal ganglia | eqtl | 5.3e-54 | -0.97 | 17:27879388:C:A |
| Brain Cerebellar Hemisphere | eqtl | 2.7e-45 | -0.76 | 17:27879388:C:A |
| Brain Cerebellum | eqtl | 2.9e-44 | -0.82 | 17:27879388:C:A |
| Breast Mammary Tissue | eqtl | 1.5e-42 | -0.83 | 17:27879388:C:A |
| Pancreas | eqtl | 8.7e-42 | -1.08 | 17:27879388:C:A |
| Brain Putamen basal ganglia | eqtl | 8.2e-41 | -0.90 | 17:27879388:C:A |
| Thyroid | eqtl | 2.6e-40 | -0.75 | 17:27879388:C:A |
| Brain Caudate basal ganglia | eqtl | 1.5e-38 | -0.85 | 17:27879388:C:A |
| Brain Hypothalamus | eqtl | 1.6e-33 | -0.94 | 17:27879388:C:A |
| Stomach | eqtl | 1.2e-32 | -0.78 | 17:27879388:C:A |
| Colon Sigmoid | eqtl | 3.5e-31 | -0.67 | 17:27879388:C:A |
| Artery Aorta | eqtl | 4.2e-29 | -0.70 | 17:27895494:G:A |
FANTOM5 promoters
5 alternative TSS:
| Promoter ID | TPM avg | Samples expressed |
|---|---|---|
| 164964 | 8.5358 | 227 |
| 164961 | 0.1287 | 21 |
| 164960 | 0.0832 | 17 |
| 164965 | 0.0786 | 14 |
| 164962 | 0.0766 | 21 |
Top tissues by expression
showing 100 of 281 tissues by Bgee expression score (0-100, higher = more expressed):
| Tissue | Anatomy ID | Expression score | Quality |
|---|---|---|---|
| cartilage tissue | UBERON:0002418 | 94.55 | gold quality |
| olfactory segment of nasal mucosa | UBERON:0005386 | 89.37 | gold quality |
| mucosa of paranasal sinus | UBERON:0005030 | 83.14 | silver quality |
| mucosa of transverse colon | UBERON:0004991 | 78.91 | gold quality |
| rectum | UBERON:0001052 | 78.33 | gold quality |
| vermiform appendix | UBERON:0001154 | 77.76 | gold quality |
| male germ line stem cell (sensu Vertebrata) in testis | CL:0000089 ∩ UBERON:0000473 | 72.81 | silver quality |
| caecum | UBERON:0001153 | 71.55 | gold quality |
| prefrontal cortex | UBERON:0000451 | 69.81 | gold quality |
| duodenum | UBERON:0002114 | 68.57 | gold quality |
| right frontal lobe | UBERON:0002810 | 68.40 | gold quality |
| nasal cavity mucosa | UBERON:0001826 | 68.37 | gold quality |
| small intestine | UBERON:0002108 | 67.13 | gold quality |
| small intestine Peyer’s patch | UBERON:0003454 | 67.03 | gold quality |
| transverse colon | UBERON:0001157 | 66.91 | gold quality |
| colonic epithelium | UBERON:0000397 | 65.38 | silver quality |
| Brodmann (1909) area 9 | UBERON:0013540 | 65.14 | gold quality |
| dorsolateral prefrontal cortex | UBERON:0009834 | 64.91 | gold quality |
| frontal cortex | UBERON:0001870 | 64.53 | gold quality |
| parotid gland | UBERON:0001831 | 64.02 | gold quality |
| neocortex | UBERON:0001950 | 63.13 | gold quality |
| Brodmann (1909) area 10 | UBERON:0013541 | 62.90 | gold quality |
| jejunal mucosa | UBERON:0000399 | 62.05 | gold quality |
| frontal pole | UBERON:0002795 | 62.00 | gold quality |
| intestine | UBERON:0000160 | 61.33 | gold quality |
| ventricular zone | UBERON:0003053 | 60.66 | gold quality |
| tendon of biceps brachii | UBERON:0008188 | 60.61 | gold quality |
| cingulate cortex | UBERON:0003027 | 60.41 | gold quality |
| endometrium epithelium | UBERON:0004811 | 60.31 | gold quality |
| upper lobe of left lung | UBERON:0008952 | 60.28 | gold quality |
| anterior cingulate cortex | UBERON:0009835 | 60.14 | gold quality |
| buccal mucosa cell | CL:0002336 | 59.95 | gold quality |
| large intestine | UBERON:0000059 | 59.83 | gold quality |
| colon | UBERON:0001155 | 59.64 | gold quality |
| cortical plate | UBERON:0005343 | 59.45 | gold quality |
| cerebral cortex | UBERON:0000956 | 59.24 | gold quality |
| right lung | UBERON:0002167 | 59.19 | gold quality |
| ganglionic eminence | UBERON:0004023 | 58.88 | gold quality |
| middle frontal gyrus | UBERON:0002702 | 58.82 | gold quality |
| decidua | UBERON:0002450 | 58.66 | gold quality |
| upper lobe of lung | UBERON:0008948 | 58.41 | gold quality |
| smooth muscle tissue | UBERON:0001135 | 58.21 | gold quality |
| paraflocculus | UBERON:0005351 | 58.14 | gold quality |
| medial globus pallidus | UBERON:0002477 | 57.65 | gold quality |
| lymph node | UBERON:0000029 | 56.72 | gold quality |
| telencephalon | UBERON:0001893 | 56.42 | gold quality |
| pancreatic ductal cell | CL:0002079 | 56.13 | silver quality |
| forebrain | UBERON:0001890 | 55.86 | gold quality |
| ileal mucosa | UBERON:0000331 | 55.78 | gold quality |
| adult mammalian kidney | UBERON:0000082 | 55.43 | gold quality |
| colonic mucosa | UBERON:0000317 | 55.39 | gold quality |
| metanephros cortex | UBERON:0010533 | 55.19 | gold quality |
| brain | UBERON:0000955 | 55.13 | gold quality |
| adenohypophysis | UBERON:0002196 | 55.02 | gold quality |
| central nervous system | UBERON:0001017 | 54.95 | gold quality |
| amygdala | UBERON:0001876 | 54.83 | gold quality |
| pituitary gland | UBERON:0000007 | 54.74 | gold quality |
| cerebellar hemisphere | UBERON:0002245 | 54.61 | gold quality |
| cerebellar cortex | UBERON:0002129 | 54.58 | gold quality |
| embryo | UBERON:0000922 | 54.36 | gold quality |
| right hemisphere of cerebellum | UBERON:0014890 | 54.28 | gold quality |
| hindlimb stylopod muscle | UBERON:0004252 | 54.20 | gold quality |
| mucosa of sigmoid colon | UBERON:0004993 | 54.06 | gold quality |
| cerebellar vermis | UBERON:0004720 | 54.00 | gold quality |
| globus pallidus | UBERON:0001875 | 53.91 | gold quality |
| cerebellum | UBERON:0002037 | 53.90 | gold quality |
| primary visual cortex | UBERON:0002436 | 53.70 | gold quality |
| gall bladder | UBERON:0002110 | 53.49 | gold quality |
| lung | UBERON:0002048 | 53.42 | gold quality |
| muscle of leg | UBERON:0001383 | 53.21 | gold quality |
| nucleus accumbens | UBERON:0001882 | 53.04 | gold quality |
| tibial nerve | UBERON:0001323 | 53.00 | gold quality |
| muscle organ | UBERON:0001630 | 52.52 | gold quality |
| Brodmann (1909) area 46 | UBERON:0006483 | 52.47 | gold quality |
| hair follicle | UBERON:0002073 | 52.43 | gold quality |
| jejunum | UBERON:0002115 | 52.19 | gold quality |
| caudate nucleus | UBERON:0001873 | 52.09 | gold quality |
| metanephros | UBERON:0000081 | 52.02 | gold quality |
| hypothalamus | UBERON:0001898 | 51.97 | gold quality |
| quadriceps femoris | UBERON:0001377 | 51.94 | gold quality |
| deltoid | UBERON:0001476 | 51.93 | gold quality |
| muscle tissue | UBERON:0002385 | 51.92 | gold quality |
| gastrocnemius | UBERON:0001388 | 51.91 | gold quality |
| putamen | UBERON:0001874 | 51.83 | gold quality |
| cortex of kidney | UBERON:0001225 | 51.80 | gold quality |
| thymus | UBERON:0002370 | 51.66 | silver quality |
| sigmoid colon | UBERON:0001159 | 51.55 | gold quality |
| kidney | UBERON:0002113 | 51.38 | gold quality |
| tibial artery | UBERON:0007610 | 51.01 | gold quality |
| popliteal artery | UBERON:0002250 | 50.93 | gold quality |
| muscle layer of sigmoid colon | UBERON:0035805 | 50.89 | gold quality |
| placenta | UBERON:0001987 | 50.85 | gold quality |
| vastus lateralis | UBERON:0001379 | 50.84 | gold quality |
| primordial germ cell in gonad | CL:0000670 ∩ UBERON:0000991 | 50.58 | silver quality |
| epithelial cell of pancreas | CL:0000083 | 50.53 | gold quality |
| occipital lobe | UBERON:0002021 | 50.46 | gold quality |
| left adrenal gland cortex | UBERON:0035825 | 50.45 | gold quality |
| right coronary artery | UBERON:0001625 | 50.32 | gold quality |
| skeletal muscle tissue | UBERON:0001134 | 50.27 | gold quality |
| left adrenal gland | UBERON:0001234 | 50.05 | gold quality |
Single-cell (SCXA)
Detected in 1 experiment(s), a significant marker in 1.
| Experiment | Marker? | Max mean expression |
|---|---|---|
| E-ANND-3 | yes | 4.03 |
HPA expression
RNA tissue specificity: Group enriched
showing 60 of 102 HPA tissues / cells by nTPM:
| Tissue / cell | Axis | nTPM | Protein (IHC) |
|---|---|---|---|
| Small intestine | tissue | 19.6 | not detected |
| Appendix | tissue | 13.8 | medium |
| Duodenum | tissue | 11.0 | low |
| Rectum | tissue | 8.2 | medium |
| Colon | tissue | 6.3 | medium |
| Urinary bladder | tissue | 3.3 | not detected |
| Cerebral cortex | tissue | 2.1 | low |
| Postcentral gyrus | tissue | 2.1 | |
| Insular cortex | tissue | 2.1 | |
| Testis | tissue | 1.9 | high |
| Prefrontal cortex | tissue | 1.7 | |
| Basal ganglia | tissue | 1.7 | low |
| Retrosplenial and cingulate cortex | tissue | 1.7 | |
| Smooth muscle | tissue | 1.6 | low |
| Motor cortex | tissue | 1.6 | |
| Putamen | tissue | 1.6 | |
| Hippocampal formation | tissue | 1.6 | |
| Ventral forebrain | tissue | 1.6 | |
| Retrosplenial cortex | tissue | 1.6 | |
| Temporal cortex | tissue | 1.6 | |
| Entorhinal cortex | tissue | 1.5 | |
| Amygdala | tissue | 1.4 | |
| Septum | tissue | 1.4 | |
| Somatosensory cortex | tissue | 1.4 | |
| Pituitary gland | tissue | 1.3 | |
| Occipital cortex | tissue | 1.3 | |
| Testis | tissue | 1.2 | not detected |
| Olfactory bulb | tissue | 1.2 | |
| Hypothalamus | tissue | 1.1 | |
| Lung | tissue | 1.1 | not detected |
| Corpus callosum | tissue | 0.9 | |
| Spinal cord | tissue | 0.8 | |
| Periaqueductal gray | tissue | 0.8 | |
| Pons | tissue | 0.7 | |
| Adipose tissue | tissue | 0.7 | not detected |
| Medulla oblongata | tissue | 0.7 | |
| Superior colliculi | tissue | 0.7 | |
| Lymph node | tissue | 0.6 | not detected |
| Skeletal muscle | tissue | 0.6 | low |
| Midbrain | tissue | 0.6 | |
| Thalamus | tissue | 0.6 | |
| Substantia nigra | tissue | 0.6 | |
| Ovary | tissue | 0.5 | not detected |
| Tongue | tissue | 0.5 | |
| Frontal cortex | tissue | 0.5 | |
| Nucleus accumbens | tissue | 0.4 | |
| Placenta | tissue | 0.4 | not detected |
| Cerebellum | tissue | 0.4 | not detected |
| Thyroid gland | tissue | 0.3 | not detected |
| Gallbladder | tissue | 0.3 | not detected |
| Kidney | tissue | 0.3 | low |
| Locus coeruleus | tissue | 0.3 | |
| Hippocampus | tissue | 0.3 | not detected |
| Fallopian tube | tissue | 0.3 | not detected |
| Caudate putamen | tissue | 0.3 | |
| Cerebral cortex | tissue | 0.3 | not detected |
| Motor cortex | tissue | 0.3 | |
| Basal ganglia | tissue | 0.3 | not detected |
| Hippocampal formation | tissue | 0.3 | |
| Postcentral gyrus | tissue | 0.3 |
Brain sub-regions (HPA Brain Atlas): detected in 359; highest nTPM — Precentral gyrus (1.8), Precentral gyrus, middle (1.7), Postcentral gyrus, middle (1.6), Subiculum (1.6), Transversal temporal gyrus, anterior (1.4).
Regulation
Is transcription factor: no
miRNA regulators (miRDB)
Targeting NOS2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).
showing 30 of 55 miRNAs:
| miRNA | Max score | Avg score | miRNA target_count |
|---|---|---|---|
| HSA-MIR-5692A | 100.00 | 74.40 | 6850 |
| HSA-MIR-559 | 99.95 | 72.28 | 3609 |
| HSA-MIR-548AB | 99.95 | 71.31 | 3488 |
| 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 |
| HSA-MIR-548H-5P | 99.94 | 71.24 | 3488 |
| HSA-MIR-548I | 99.94 | 71.25 | 3481 |
| HSA-MIR-548J-5P | 99.94 | 71.14 | 3489 |
| HSA-MIR-548O-5P | 99.94 | 71.24 | 3488 |
| HSA-MIR-548W | 99.94 | 71.24 | 3488 |
| HSA-MIR-548Y | 99.94 | 71.28 | 3514 |
| HSA-MIR-4525 | 99.94 | 64.38 | 675 |
| HSA-MIR-5010-5P | 99.94 | 64.11 | 705 |
| HSA-MIR-1297 | 99.91 | 73.41 | 3162 |
| HSA-MIR-609 | 99.82 | 64.26 | 505 |
| HSA-MIR-34B-5P | 99.78 | 67.56 | 1175 |
| HSA-MIR-449C-5P | 99.78 | 67.63 | 1168 |
Functional genomics
gnomAD constraint: pLI 2.06e-22, LOEUF 0.858, missense Z 2.17 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD
Regional missense constraint (gnomAD)
ENST00000313735 splits into 3 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD
| Region (GRCh38) | Missense obs / exp | o/e | Constrained |
|---|---|---|---|
| 17:27,757,249–27,774,380 | 782 / 909.9 | 0.86 | no |
| 17:27,774,381–27,778,715 | 15 / 41.6 | 0.36 | no |
| 17:27,778,716–27,798,809 | 440 / 545.4 | 0.81 | no |
Literature-anchored findings (GeneRIF, showing 40)
- The specific NOS2 inhibitor, 1400W, sensitizes HepG2 cells to genotoxic, oxidative, xenobiotic, and endoplasmic reticulum stresses (PMID:11761338)
- Inos enzyme overexpressioin is an early event in esophageal carcinogenesis and useful biomarkers for early detection. (PMID:11783017)
- Human renal epithelial cells express iNOS in response to cytokines but not bacteria (PMID:11849384)
- The human alveolar type II epithelium-like cell line A549 expresses nitric oxide synthase type 2 (NOS2) (PMID:11880293)
- Immunohistochemical expression of iNOS in colorectal carcinoma (PMID:11956620)
- Increased expression of iNOS may be responsible for gastric carcinogenesis and tumor aggressiveness of gastric cancer and correlates significantly with lymph node metastasis in northern China. (PMID:11978184)
- demonstrated that the iNOS gene was actively transcribed in cutaneous leishmaniasis lesions (PMID:11985871)
- Inducible nitric oxide synthase is expressed in normal human melanocytes but not in melanoma cells (PMID:12060397)
- epithelial iNOS binds to EPB50 which directs vectorial nitric oxide output (PMID:12080081)
- allelic polymorphism of the inducible nitric oxide synthase (iNOS) gene associated with retinopathy in an Asian Indian population (PMID:12081717)
- enzyme expressed in septic patients is nitrated on selected tyrosine residues; implications for enzymic activity (PMID:12097137)
- expression of inducible nitric oxide synthase in skin lesions of patients with cutaneous leishmaniasis (PMID:12117977)
- Data show that prostacyclin receptor mediated increases in cAMP play a role in enhancing LPS/IFN-gamma-induced iNOS expression in human monocytes/macrophages and may contribute to the increased production of NO during peritonitis. (PMID:12119468)
- expression is increased in malaria, thus producing more nitric oxide (PMID:12125143)
- inducible nitric oxide synthase promoter polymorphism in rheumatoid arthritis (PMID:12140750)
- iNOS is induced by HIV-1 tat in astrocytes and may play a role in HIV-associated dementia (PMID:12167619)
- expressions of iNOS and VEGF may serve as indexes for evaluating staging of gastric carcinoma and forecasting its risk of metastasis (PMID:12174362)
- iNOS is subject to ubiquitination and ubiquitination is required for its degradation. (PMID:12221289)
- EGF protects against oxidative disruption of the intestinal barrier by stabilizing the cytoskeleton in large part through the activation of PKC-zeta and downregulation of iNOS (PMID:12223351)
- These results suggest that IL-15 is a potent regulator of iNOS expression by HGEC and involved in innate immunity in the mucosal epithelium. (PMID:12237122)
- Data demonstrate that the PI3-kinase signaling pathway is involved in basal trophoblast motility and that both mitogen-activated protein kinase and PI3-kinase signaling pathways are important in HGF-stimulated motility and iNOS expression. (PMID:12243747)
- Synovial fluid leucocytes, in particular granulocytes, express iNOS and may thus contribute to intra-articular NO production in arthritis. (PMID:12296866)
- iNOS may not correlate with cancer cell-proliferative activity or apoptosis (PMID:12374680)
- role of NF-kappa B-repressing factor (NRF) in basal repression of the hiNOS gene (PMID:12381793)
- strong upregulation of iNOS might contribute to inflammatory processes in fulminant hepatic failure (PMID:12399227)
- Activation might be associated with malignant potential of epithelial odontogenic tumors (PMID:12406306)
- Association analysis of five polymorphic microsatellite markers in cluster headache (CH) patients reveals that genetic variations in NOS2A do not contribute greatly to CH susceptibility. (PMID:12421162)
- hepatic inducible nitric oxide synthase staining was significantly more intense in patients with chronic viral hepatitis; these results suggest that inducible nitric oxide synthase may have a critical role in the pathogenesis of chronic viral hepatitis (PMID:12431203)
- NOS2 promoter -1173 C–>T single nucleotide polymorphism is associated with protection against cerebral malaria and severe malarial anaemia (PMID:12433515)
- Increased intrahepatic iNOS expression and nitrotyrosine accumulation in biliary cirrhosis and autoimmune hepatitis, related to histological severity of liver disease. (PMID:12445411)
- nitric oxide synthases(inducible, brain and endothelial) were expressed in human pregnant term uterus and did not change in the myometrium during labor (PMID:12445599)
- A positive correlation was found between the positive expression of iNOS mRNA and invasive growth as well as neck lymph node metastatsis of squamous cell carcinoma of tongue. (PMID:12452003)
- Data show that nitric oxide produced by inducible nitric oxide synthase (iNOS) increases the activity of cyclooxygenase-2 (COX-2) pathways in head and neck squamous cell carcinomas, and this effect is probably mediated by endocellular cGMP. (PMID:12459168)
- inducible nitric oxide synthase-cyclooxygenase 2 interactions are involved in tumor cell angiogenesis and migration (PMID:12462194)
- Upregulation of iNOS in myelodysplastic syndromes has no significant correlation with apoptosis. (PMID:12486325)
- Immunolocalization of inducible nitric oxide synthase in gingiva in localized juvenile periodontitis patients. iNOS in gingivitis. Macrophages expressed high levels of iNOS. (PMID:12489192)
- Altered genetic control of NOS2 transcription may be a risk factor for SLE among African-American females. (PMID:12508391)
- study demonstrate that expression of the MDA-7 tumor suppressor can negatively regulate iNOS expression in malignant melanoma cell lines (PMID:12533668)
- A single haplotype, uniquely defined by the NOS2A-1659T allele, was associated with cerebral malaria by a transmission disequilibrium . (PMID:12552317)
- upregulation of hepatic iNOS, associated with peroxisomal localization, is an early molecular early molecular response to hemorrhagic shock (PMID:12578118)
Cross-species orthologs
5 orthologs
| Organism | Symbol | Gene ID |
|---|---|---|
| danio_rerio | nos2a | ENSDARG00000026925 |
| danio_rerio | nos2b | ENSDARG00000031976 |
| mus_musculus | Nos2 | ENSMUSG00000020826 |
| rattus_norvegicus | Nos2 | ENSRNOG00000057443 |
| rattus_norvegicus | Nos2-ps1 | ENSRNOG00000078225 |
Paralogs (5): NOS1 (ENSG00000089250), MTRR (ENSG00000124275), POR (ENSG00000127948), NOS3 (ENSG00000164867), NDOR1 (ENSG00000188566)
Mouse-model phenotypes
Observed phenotypes of the mouse ortholog (MGI:97361) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 153 distinct phenotype terms.
| Mouse phenotype (MP) | Records |
|---|---|
| hyperglycemia | 3 |
| abnormal glucose homeostasis | 3 |
| increased circulating creatinine level | 3 |
| increased body weight | 2 |
| increased circulating triglyceride level | 2 |
| decreased inflammatory response | 2 |
| increased susceptibility to bacterial infection | 2 |
| abnormal osteoclast morphology | 2 |
| abnormal heart ventricle morphology | 2 |
| increased T cell proliferation | 2 |
| increased interferon-gamma secretion | 2 |
| decreased susceptibility to endotoxin shock | 2 |
| abnormal blood homeostasis | 2 |
| abnormal trabecular bone morphology | 1 |
| abnormal circulating glucose level | 1 |
| abnormal circulating serum albumin level | 1 |
| abnormal systemic arterial blood pressure | 1 |
| abnormal heart morphology | 1 |
| decreased digestive secretion | 1 |
| abnormal immune system morphology | 1 |
| abnormal corpus callosum morphology | 1 |
| abnormal uterus morphology | 1 |
| abnormal testis morphology | 1 |
| abnormal eating behavior | 1 |
| abnormal sleep pattern | 1 |
+128 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 |
|---|---|---|---|
| Escherichia coli APEC O1 | A1AEV0 | 100.0% | Diamond |
| Yersinia pestis Pestoides F | A4TPY5 | 100.0% | Diamond |
| Escherichia coli O139:H28 str. E24377A | A7ZQK7 | 100.0% | Diamond |
| Escherichia coli ATCC 8739 | B1IU77 | 100.0% | Diamond |
| Staphylococcus aureus | P0A004 | 100.0% | Diamond |
| Staphylococcus aureus subsp. aureus Mu50 | P0A092 | 100.0% | Diamond |
| Staphylococcus aureus subsp. aureus N315 | P0A093 | 100.0% | Diamond |
| Staphylococcus aureus subsp. aureus MW2 | P0A094 | 100.0% | Diamond |
| Shigella flexneri 5 str. 8401 | Q0T1I8 | 100.0% | Diamond |
| Escherichia coli 536 | Q0TEA2 | 100.0% | Diamond |
| Yersinia pestis Antiqua | Q1C3Z0 | 100.0% | Diamond |
| Yersinia pestis Nepal516 | Q1CLS8 | 100.0% | Diamond |
| Escherichia coli UTI89 | Q1R7T4 | 100.0% | Diamond |
| Staphylococcus aureus subsp. aureus COL | Q5HEK7 | 100.0% | Diamond |
| Staphylococcus aureus subsp. aureus MSSA476 | Q6G818 | 100.0% | Diamond |
| Shigella flexneri | Q83QD9 | 100.0% | Diamond |
| Yersinia pestis | Q8ZBN6 | 100.0% | Diamond |
| Escherichia coli K-12 | P38038 | 99.8% | Diamond |
| Shigella boydii Sb227 | Q31XM4 | 99.8% | Diamond |
| Escherichia coli CFT073 | Q8FEI7 | 99.8% | Diamond |
| Vibrio cholerae O395 | A5F3I4 | 99.7% | Diamond |
| Yersinia pseudotuberculosis IP 31758 | A7FLZ0 | 99.7% | Diamond |
| Shigella sonnei Ss046 | Q3YY94 | 99.7% | Diamond |
| Vibrio cholerae O1 biovar El Tor str. N16961 | Q9KUX4 | 99.7% | Diamond |
| Escherichia coli HS | A8A3P5 | 99.3% | Diamond |
| Escherichia coli O157:H7 | Q8X7U1 | 99.3% | Diamond |
| Shigella dysenteriae Sd197 | Q32CG3 | 99.0% | Diamond |
| Yersinia pseudotuberculosis IP 32953 | Q66ED4 | 98.9% | Diamond |
| Staphylococcus aureus subsp. aureus MRSA252 | Q6GFE2 | 98.6% | Diamond |
| Salmonella enterica subsp. enterica serovar Paratyphi B str. SPB7 | A9N2E6 | 98.5% | Diamond |
| Salmonella enterica subsp. enterica serovar Typhimurium str. LT2 | P38039 | 98.5% | Diamond |
| Shewanella sp. MR-4 | Q0HFL6 | 98.5% | Diamond |
| Shewanella sp. MR-7 | Q0HYB4 | 98.5% | Diamond |
| Neisseria meningitidis 053442 | A9LZ73 | 98.3% | Diamond |
| Neisseria meningitidis Z2491 | Q9JUD8 | 98.3% | Diamond |
| Shewanella sp. ANA-3 | A0KTH4 | 98.2% | Diamond |
| Neisseria meningitidis FAM18 | A1KU06 | 98.0% | Diamond |
| Salmonella enterica subsp. enterica serovar Paratyphi A str. ATCC 9150 | Q5PEH7 | 97.8% | Diamond |
| Salmonella enterica subsp. enterica serovar Typhi | Q8Z458 | 97.8% | Diamond |
| Bos taurus | Q27995 | 97.0% | 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 |
|---|---|---|
| LYRM9 | protein-coding | 201229 |
| LINC01992 | ncRNA | 105371708 |
Protein
Protein identifiers
Nitric oxide synthase, inducible — P35228 (reviewed: P35228)
Alternative names: Hepatocyte NOS, Inducible NO synthase, NOS type II, Peptidyl-cysteine S-nitrosylase NOS2
All UniProt accessions (6): P35228, A0A2R8YDS4, A0A8V8TKX9, A0A8V8TKZ7, A0A8V8TLB1, A0A8V8TMI7
UniProt curated annotations — full annotation on UniProt →
Function. Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body. In macrophages, NO mediates tumoricidal and bactericidal actions. Also has nitrosylase activity and mediates cysteine S-nitrosylation of cytoplasmic target proteins such PTGS2/COX2. As component of the iNOS-S100A8/9 transnitrosylase complex involved in the selective inflammatory stimulus-dependent S-nitrosylation of GAPDH on ‘Cys-247’ implicated in regulation of the GAIT complex activity and probably multiple targets including ANXA5, EZR, MSN and VIM. Involved in inflammation, enhances the synthesis of pro-inflammatory mediators such as IL6 and IL8.
Subunit / interactions. Homodimer. Interacts with NHERF1. Interacts with GAPDH; induced by oxidatively-modified low-densitity lipoprotein (LDL(ox)). Interacts with S100A8 and S100A9 to form the iNOS-S100A8/9 transnitrosylase complex. Interacts with SPSB1, SPSB2 and SPSB4. Interacts with ELOC and CUL5 in the presence of SPSB1 or SPSB2 or SPSB4. Forms a complex with ASL, ASS1 and HSP90AA1; the complex regulates cell-autonomous L-arginine synthesis and citrulline recycling while channeling extracellular L-arginine to nitric oxide synthesis pathway.
Subcellular location. Cytoplasm. Cytosol.
Tissue specificity. Expressed in the liver, retina, bone cells and airway epithelial cells of the lung. Not expressed in the platelets. Expressed in chondrocytes.
Post-translational modifications. Polyubiquitinated; mediated by SPSB1, SPSB2 and SPSB4, leading to proteasomal degradation.
Activity regulation. Regulated by calcium/calmodulin. Aspirin inhibits expression and function of this enzyme and effects may be exerted at the level of translational/post-translational modification and directly on the catalytic activity.
Cofactor. Binds 1 FAD. Binds 1 FMN. Tetrahydrobiopterin (BH4). May stabilize the dimeric form of the enzyme.
Induction. By endotoxins and cytokines. Induced by IFNG/IFN-gamma acting synergistically with bacterial lipopolysaccharides (LPS), TNF or IL1B/interleukin-1 beta. Down-regulated by zinc due to inhibition of NF-kappa-B transactivation activity. By oxidatively-modified low-densitity lipoprotein (LDL(ox)).
Polymorphism. Genetic variations in NOS2 are involved in resistance to malaria [MIM:611162].
Similarity. Belongs to the NOS family.
Isoforms (2)
| UniProt ID | Names | Canonical? |
|---|---|---|
| P35228-1 | 1 | yes |
| P35228-2 | 2 |
RefSeq proteins (1): NP_000616* (*=MANE)
Domains & families (InterPro)
| ID | Name | Type |
|---|---|---|
| IPR001094 | Flavdoxin-like | Domain |
| IPR001433 | OxRdtase_FAD/NAD-bd | Domain |
| IPR001709 | Flavoprot_Pyr_Nucl_cyt_Rdtase | Domain |
| IPR003097 | CysJ-like_FAD-binding | Domain |
| IPR004030 | NOS_N | Domain |
| IPR008254 | Flavodoxin/NO_synth | Domain |
| IPR012144 | NOS_euk | Family |
| IPR017927 | FAD-bd_FR_type | Domain |
| IPR017938 | Riboflavin_synthase-like_b-brl | Homologous_superfamily |
| IPR023173 | NADPH_Cyt_P450_Rdtase_alpha | Homologous_superfamily |
| IPR029039 | Flavoprotein-like_sf | Homologous_superfamily |
| IPR036119 | NOS_N_sf | Homologous_superfamily |
| IPR039261 | FNR_nucleotide-bd | Homologous_superfamily |
| IPR044940 | NOS_dom_2 | Homologous_superfamily |
| IPR044943 | NOS_dom_1 | Homologous_superfamily |
| IPR044944 | NOS_dom_3 | Homologous_superfamily |
| IPR050607 | NOS | Family |
Pfam: PF00175, PF00258, PF00667, PF02898
Enzyme classification (BRENDA)
- EC 1.14.13.39 — nitric-oxide synthase (NADPH) (BRENDA: 31 organisms, 140 substrates, 179 inhibitors, 88 Km, 25 kcat entries)
Substrate kinetics (BRENDA)
11 substrates with measured Km, best-characterized 11. Km ranges are aggregated across organisms/conditions.
| Substrate | Km (mM) | Measurements |
|---|---|---|
| L-ARGININE | 0.0019–68.5 | 28 |
| NADPH | 0.0003–0.0041 | 9 |
| TETRAHYDROBIOPTERIN | — | 6 |
| ADRIAMYCIN | 0.012–0.078 | 5 |
| MENADIONE | 0.01–0.041 | 5 |
| MITOMYCIN C | 0.0073–0.055 | 5 |
| NGAMMA-HYDROXY-L-ARGININE | 0.019–0.129 | 5 |
| 2’,3’-DIALDEHYDE-NADPH | 0.0008 | 1 |
| CALMODULIN | — | 1 |
| NITROBLUE TETRAZOLIUM | 0.016 | 1 |
| NITRIC OXIDE | — | 0 |
Catalyzed reactions (Rhea)
- 2 L-arginine + 3 NADPH + 4 O2 + H(+) = 2 L-citrulline + 2 nitric oxide + 3 NADP(+) + 4 H2O (RHEA:19897)
UniProt features (143 total): binding site 45, helix 36, strand 26, sequence conflict 15, sequence variant 5, turn 4, modified residue 4, domain 2, splice variant 2, chain 1, region of interest 1, short sequence motif 1, mutagenesis site 1
Structure
Experimental structures (PDB)
13 structures by resolution:
| PDB | Title | Method | Resolution (Å) |
|---|---|---|---|
| 6JWM | Crystal structure of the SPRY domain of SPSB2 in complex with cR7, a potent cyclic … | X-RAY DIFFRACTION | 1.23 |
| 6KEY | Structural basis for the regulation of inducible nitric oxide synthase (iNOS) by the SPRY … | X-RAY DIFFRACTION | 1.24 |
| 5XN3 | Crystal structure of SPSB2 in complex with a rational designed RGD containing cyclic … | X-RAY DIFFRACTION | 1.34 |
| 6JWN | Crystal structure of the SPRY domain of SPSB2 in complex with cR9, a cyclic peptide … | X-RAY DIFFRACTION | 1.61 |
| 3E7G | Structure of human INOSOX with inhibitor AR-C95791 | X-RAY DIFFRACTION | 2.2 |
| 4NOS | HUMAN INDUCIBLE NITRIC OXIDE SYNTHASE WITH INHIBITOR | X-RAY DIFFRACTION | 2.25 |
| 3HR4 | Human iNOS Reductase and Calmodulin Complex | X-RAY DIFFRACTION | 2.5 |
| 1NSI | HUMAN INDUCIBLE NITRIC OXIDE SYNTHASE, ZN-BOUND, L-ARG COMPLEX | X-RAY DIFFRACTION | 2.55 |
| 3EJ8 | Structure of double mutant of human iNOS oxygenase domain with bound immidazole | X-RAY DIFFRACTION | 2.55 |
| 2NSI | HUMAN INDUCIBLE NITRIC OXIDE SYNTHASE, ZN-FREE, SEITU COMPLEX | X-RAY DIFFRACTION | 3 |
| 4CX7 | Structure of human iNOS heme domain in complex with (R)-6-(3-AMINO-2-(5-(2-(6-AMINO-4- … | X-RAY DIFFRACTION | 3.16 |
| 2LL6 | Solution NMR structure of CaM bound to iNOS CaM binding domain peptide | SOLUTION NMR | |
| 5TP6 | Solution structure of the CaM34 with the iNOS CaM binding domain peptide | SOLUTION NMR |
Predicted structure (AlphaFold)
| Model | pLDDT | Fraction very-high |
|---|---|---|
| AF-P35228-F1 | 85.66 | 0.66 |
Human Protein Atlas
Protein class: Enzymes, ENZYME proteins, Oxidoreductases, Metabolic proteins, Predicted intracellular proteins, Plasma proteins, Cancer-related genes, Candidate cancer biomarkers, FDA approved drug targets, Small molecule drugs, Human disease related genes
Protein evidence: Evidence at protein level
Antibody reliability (HPA): IH enhanced
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 (45)
| Position | Role |
|---|---|
| 372 | L-arginine |
| 373 | L-arginine |
| 377 | L-arginine |
| 381 | (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin |
| 462 | (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin |
| 463 | (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin |
| 476 | (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin |
| 491 | heme b |
| 545 | FMN |
| 546 | FMN |
| 547 | FMN |
| 549 | FMN |
| 550 | FMN |
| 591 | FMN |
| 592 | FMN |
| 628 | FMN |
| 633 | FMN |
| 635 | FMN |
| 661 | FMN |
| 665 | FMN |
| 750 | NADP(+) |
| 772 | FAD |
| 906 | FAD |
| 908 | FAD |
| 909 | FAD |
| 924 | FAD |
| 926 | FAD |
| 929 | NADP(+) |
| 930 | FAD |
| 943 | FAD |
| 944 | FAD |
| 945 | FAD |
| 984 | NADP(+) |
| 1017 | NADP(+) |
| 1046 | NADP(+) |
| 1047 | NADP(+) |
| 1053 | NADP(+) |
| 1055 | NADP(+) |
| 1057 | NADP(+) |
| 1090 | NADP(+) |
| 110 | Zn(2+) |
| 115 | Zn(2+) |
| 118 | (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin |
| 200 | heme b |
| 263 | L-arginine |
Post-translational modifications (4)
| Type | Positions |
|---|---|
| Phosphoserine | 234, 578, 892 |
| Phosphotyrosine | 575 |
Mutagenesis-validated functional residues (1)
| Position | Phenotype |
|---|---|
| 27 | loss of interaction with spsb1 and spsb4. |
Function
Pathways and Gene Ontology
Reactome pathways
4 curated (TAS) of 18; 7 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).
18 pathways:
| ID | Pathway | Evidence |
|---|---|---|
| R-HSA-9636249 | Inhibition of nitric oxide production ⚕ | curated |
| R-HSA-6785807 | Interleukin-4 and Interleukin-13 signaling | curated |
| R-HSA-392154 | Nitric oxide stimulates guanylate cyclase | curated |
| R-HSA-1222556 | ROS and RNS production in phagocytes | curated |
| R-HSA-9824439 | Bacterial Infection Pathways ⚕ | — |
| R-HSA-1643685 | Disease ⚕ | — |
| R-HSA-9635486 | Infection with Mycobacterium tuberculosis ⚕ | — |
| R-HSA-5663205 | Infectious disease ⚕ | — |
| R-HSA-9637690 | Response of Mtb to phagocytosis ⚕ | — |
| R-HSA-9637687 | Suppression of phagosomal maturation ⚕ | — |
| R-HSA-1280215 | Cytokine Signaling in Immune system | — |
| R-HSA-109582 | Hemostasis | — |
| R-HSA-168256 | Immune System | — |
| R-HSA-168249 | Innate Immune System | — |
| R-HSA-9033241 | Peroxisomal protein import | electronic |
| R-HSA-418346 | Platelet homeostasis | — |
| R-HSA-9609507 | Protein localization | — |
| R-HSA-449147 | Signaling by Interleukins | — |
MSigDB gene sets: 351 (showing top):
GOBP_CIRCADIAN_RHYTHM, LEE_NEURAL_CREST_STEM_CELL_DN, MORF_FLT1, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_REGULATION_OF_BLOOD_PRESSURE, MORF_MSH3, GOBP_CIRCULATORY_SYSTEM_PROCESS, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_INFLAMMATORY_RESPONSE, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_PAIRED_DONORS_WITH_INCORPORATION_OR_REDUCTION_OF_MOLECULAR_OXYGEN, GOBP_POSITIVE_REGULATION_OF_INTERLEUKIN_8_PRODUCTION, GOBP_RESPONSE_TO_PEPTIDE, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_CELLULAR_RESPONSE_TO_BIOTIC_STIMULUS, GOBP_ALPHA_AMINO_ACID_METABOLIC_PROCESS
GO Biological Process (24): positive regulation of leukocyte mediated cytotoxicity (GO:0001912), innate immune response in mucosa (GO:0002227), L-arginine catabolic process (GO:0006527), superoxide metabolic process (GO:0006801), nitric oxide biosynthetic process (GO:0006809), inflammatory response (GO:0006954), circadian rhythm (GO:0007623), response to bacterium (GO:0009617), response to hormone (GO:0009725), negative regulation of gene expression (GO:0010629), peptidyl-cysteine S-nitrosylation (GO:0018119), prostaglandin secretion (GO:0032310), response to lipopolysaccharide (GO:0032496), positive regulation of interleukin-6 production (GO:0032755), positive regulation of interleukin-8 production (GO:0032757), Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096), negative regulation of protein catabolic process (GO:0042177), defense response to bacterium (GO:0042742), regulation of cellular respiration (GO:0043457), cell redox homeostasis (GO:0045454), negative regulation of blood pressure (GO:0045776), regulation of insulin secretion (GO:0050796), defense response to Gram-negative bacterium (GO:0050829), regulation of cytokine production involved in inflammatory response (GO:1900015)
GO Molecular Function (12): nitric-oxide synthase activity (GO:0004517), calmodulin binding (GO:0005516), FMN binding (GO:0010181), heme binding (GO:0020037), tetrahydrobiopterin binding (GO:0034617), arginine binding (GO:0034618), protein homodimerization activity (GO:0042803), metal ion binding (GO:0046872), flavin adenine dinucleotide binding (GO:0050660), NADP binding (GO:0050661), protein binding (GO:0005515), oxidoreductase activity (GO:0016491)
GO Cellular Component (9): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), peroxisome (GO:0005777), peroxisomal matrix (GO:0005782), cytosol (GO:0005829), plasma membrane (GO:0005886), cortical cytoskeleton (GO:0030863), perinuclear region of cytoplasm (GO:0048471)
Reactome top-level categories
13 top-level categories:
| Category | Pathways |
|---|---|
| Immune System | 2 |
| Innate Immune System | 1 |
| Platelet homeostasis | 1 |
| Signaling by Interleukins | 1 |
| Protein localization | 1 |
| Suppression of phagosomal maturation | 1 |
| Hemostasis | 1 |
| Cytokine Signaling in Immune system | 1 |
| Disease | 1 |
| Bacterial Infection Pathways | 1 |
| Response of Mtb to phagocytosis | 1 |
| Infection with Mycobacterium tuberculosis | 1 |
| Infectious disease | 1 |
GO top-level categories
showing 60 of 70 GO namespaces:
| Category | Terms |
|---|---|
| cellular anatomical structure | 4 |
| defense response | 2 |
| positive regulation of cytokine production | 2 |
| anion binding | 2 |
| binding | 2 |
| cation binding | 2 |
| cytoplasm | 2 |
| leukocyte mediated cytotoxicity | 1 |
| regulation of leukocyte mediated cytotoxicity | 1 |
| positive regulation of leukocyte mediated immunity | 1 |
| positive regulation of cell killing | 1 |
| mucosal immune response | 1 |
| innate immune response | 1 |
| arginine metabolic process | 1 |
| amino acid catabolic process | 1 |
| proteinogenic amino acid catabolic process | 1 |
| reactive oxygen species metabolic process | 1 |
| biosynthetic process | 1 |
| nitric oxide metabolic process | 1 |
| rhythmic process | 1 |
| response to other organism | 1 |
| response to endogenous stimulus | 1 |
| response to chemical | 1 |
| gene expression | 1 |
| regulation of gene expression | 1 |
| negative regulation of macromolecule biosynthetic process | 1 |
| protein nitrosylation | 1 |
| prostaglandin transport | 1 |
| signal release | 1 |
| icosanoid secretion | 1 |
| lipid export from cell | 1 |
| response to molecule of bacterial origin | 1 |
| response to lipid | 1 |
| response to oxygen-containing compound | 1 |
| interleukin-6 production | 1 |
| regulation of interleukin-6 production | 1 |
| interleukin-8 production | 1 |
| regulation of interleukin-8 production | 1 |
| Fc receptor mediated stimulatory signaling pathway | 1 |
| phagocytosis | 1 |
| Fc-gamma receptor signaling pathway | 1 |
| negative regulation of catabolic process | 1 |
| protein catabolic process | 1 |
| regulation of protein catabolic process | 1 |
| negative regulation of protein metabolic process | 1 |
| response to bacterium | 1 |
| regulation of generation of precursor metabolites and energy | 1 |
| cellular respiration | 1 |
| cellular homeostasis | 1 |
| oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, NAD(P)H as one donor, and incorporation of one atom of oxygen | 1 |
| protein binding | 1 |
| ribonucleotide binding | 1 |
| tetrapyrrole binding | 1 |
| amino acid binding | 1 |
| carboxylic acid binding | 1 |
| identical protein binding | 1 |
| protein dimerization activity | 1 |
| nucleotide binding | 1 |
| adenyl nucleotide binding | 1 |
| catalytic activity | 1 |
Experimentally-supported GO annotations
GO terms backed by direct experimental evidence (ECO experimental codes) — 14 of 46 annotations. The rest are phylogenetic / computational / electronic (IEA).
14 experimentally-supported GO terms:
| GO term | NS | Evidence |
|---|---|---|
| Fc-gamma receptor signaling pathway involved in phagocytosis | BP | mutant phenotype |
| L-arginine catabolic process | BP | direct assay |
| defense response to bacterium | BP | mutant phenotype |
| negative regulation of gene expression | BP | genetic interaction |
| nitric oxide biosynthetic process | BP | direct assay |
| positive regulation of interleukin-6 production | BP | direct assay |
| positive regulation of interleukin-8 production | BP | direct assay |
| prostaglandin secretion | BP | direct assay |
| regulation of cytokine production involved in inflammatory response | BP | direct assay |
| regulation of insulin secretion | BP | mutant phenotype |
| cytoplasm | CC | direct assay |
| cytosol | CC | mutant phenotype |
| peroxisome | CC | direct assay |
| nitric-oxide synthase activity | MF | direct assay |
Protein interactions and networks
STRING
showing 15 of 2,454 interactions by confidence (×1000):
| Protein A | Protein B | Partner UniProt | Score |
|---|---|---|---|
| NOS2 | IL1B | P01584 | 867 |
| NOS2 | PTGS2 | P35354 | 857 |
| NOS2 | IFNG | P01579 | 848 |
| NOS2 | TNF | P01375 | 848 |
| NOS2 | ARG1 | P05089 | 814 |
| NOS2 | IL6 | P05231 | 802 |
| NOS2 | TLR4 | O00206 | 743 |
| NOS2 | IL10 | P22301 | 743 |
| NOS2 | NFKB1 | P19838 | 692 |
| NOS2 | ARG2 | P78540 | 679 |
| NOS2 | IL4 | P05112 | 671 |
| NOS2 | TLR2 | O60603 | 670 |
| NOS2 | IL1A | P01583 | 660 |
| NOS2 | MRC1 | P22897 | 648 |
| NOS2 | EDN1 | P05305 | 644 |
IntAct
Human interaction partners of NOS2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).
4 partners by confidence:
| Partner | Interaction type | MIscore | Records |
|---|---|---|---|
| GAPDH | physical association | 0.500 | 7 |
| S100A8 | association | 0.460 | 2 |
| ADRM1 | physical association | 0.400 | 1 |
| UCHL5 | physical association | 0.400 | 1 |
BioGRID (224 interactions; top human partners by supporting records): SPSB2 (Biochemical Activity; 13 records), SPSB1 (Affinity Capture-Western; 7 records), CALM1 (Reconstituted Complex; 5 records), FBXO45 (Affinity Capture-MS; 3 records), HSP90AA1 (Affinity Capture-MS; 3 records), RAC2 (Affinity Capture-Western; 3 records), SPSB4 (Affinity Capture-Western; 3 records), CAV1 (Co-fractionation; 2 records), CUL5 (Affinity Capture-Western; 2 records), TCEB1 (Affinity Capture-Western; 2 records), UCHL5 (Affinity Capture-Western; 2 records), ACAA1 (FRET), AGR2 (Affinity Capture-MS), AIFM1 (Affinity Capture-MS), AKR1B10 (Affinity Capture-MS)
SIGNOR signaling
9 signaling interactions:
| A | Effect | B | Mechanism |
|---|---|---|---|
| PRKAA1 | down-regulates | NOS2 | |
| MAPK3 | up-regulates | NOS2 | phosphorylation |
| SRC | up-regulates | NOS2 | phosphorylation |
| STAT1 | “up-regulates quantity by expression” | NOS2 | “transcriptional regulation” |
| NfKb-p65/p50 | “up-regulates quantity by expression” | NOS2 | “transcriptional regulation” |
| NOS2 | up-regulates | “nitric oxide” | |
| NOS2 | up-regulates | L-citrulline | |
| L-arginine | up-regulates | NOS2 | |
| NfKb-p65/p50 | up-regulates | NOS2 | “transcriptional regulation” |
Protein complexes (CORUM) (1)
Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).
1 complexes by size:
| Complex | Subunits | Members |
|---|---|---|
| iNOS-S100A8/A9 complex | 3 | S100A8, S100A9, NOS2 |
Disease & clinical
Genetic variants
Variant evidence for NOS2: 213 ClinVar records (0 pathogenic / likely pathogenic).
ClinVar
213 variants total. Per-class counts are floors (≥ shown; pagination cap):
| Classification | Count (floor) |
|---|---|
| Pathogenic | 0 |
| Likely pathogenic | 0 |
| Uncertain significance | 143 |
| Likely benign | 40 |
| Benign | 20 |
AlphaMissense
2,099 missense substitutions predicted likely pathogenic (of 7,616 scored), across 553 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 |
|---|---|---|---|
| M223 | 9 | 0.820 | 0.979 |
| F369 | 8 | 0.976 | 0.997 |
| D435 | 8 | 0.966 | 0.989 |
| F247 | 8 | 0.959 | 0.992 |
| D98 | 8 | 0.954 | 0.987 |
| D280 | 8 | 0.953 | 0.984 |
| H230 | 8 | 0.947 | 0.987 |
| D412 | 8 | 0.947 | 0.985 |
| F443 | 8 | 0.941 | 0.993 |
| D460 | 8 | 0.936 | 0.986 |
| H436 | 8 | 0.933 | 0.986 |
| H333 | 8 | 0.910 | 0.987 |
| D385 | 8 | 0.909 | 0.962 |
| N196 | 8 | 0.908 | 0.994 |
| F339 | 8 | 0.908 | 0.990 |
| H437 | 8 | 0.904 | 0.985 |
| F1128 | 8 | 0.903 | 0.989 |
| N261 | 8 | 0.900 | 0.995 |
| F565 | 8 | 0.899 | 0.981 |
| D833 | 8 | 0.899 | 0.961 |
HPA cancer prognostics
RNA cancer specificity: Group enriched (Colon Adenocarcinoma, Glioblastoma Multiforme, Lung Squamous Cell Carcinoma, Rectum Adenocarcinoma, Stomach Adenocarcinoma)
Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.
2 prognostic cancer types:
| Cancer | Prognostic | p-value |
|---|---|---|
| Kidney Renal Clear Cell Carcinoma (TCGA) | favorable | 2.97e-06 |
| Kidney Renal Clear Cell Carcinoma (validation) | favorable | 0.000338 |
Disease associations
OMIM: gene MIM:163730 | disease phenotypes:
GenCC curated gene-disease
1 curated gene-disease records:
| Disease | Classification | Inheritance | Records |
|---|---|---|---|
| schizophrenia | No Known Disease Relationship | Unknown |
Genomics England panels (PanelApp)
Clinical diagnostic gene panels including this gene (1 panels, 1 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.
1 panels:
| Panel | Rating |
|---|---|
| COVID-19 research | green |
Mondo (1): schizophrenia (MONDO:0005090)
Drugs & pharmacology
Drug and pharmacology data
Is drug target: yes
ChEMBL targets (4): CHEMBL2096621 (SELECTIVITY GROUP), CHEMBL2111350 (SELECTIVITY GROUP), CHEMBL4481 (SINGLE PROTEIN), CHEMBL4630725 (PROTEIN FAMILY)
Drugs by curated mechanism of action (ChEMBL)
Drugs whose curated ChEMBL mechanism of action targets the NOS2 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.
2 curated-mechanism drugs:
| Drug | Modality | Max phase |
|---|---|---|
| GW-274150 | Small molecule | 2 |
| KD7040 | Small molecule | 2 |
Drugs acting on a complex or family that includes this protein
Curated ChEMBL mechanism-of-action drugs whose target is a protein complex or family of ≤10 members that includes NOS2 — the drug acts on the assembly or class, not necessarily on this subunit alone.
1 drugs via a complex or family:
| Drug | Target (ChEMBL) | Members | Max phase |
|---|---|---|---|
| TILARGININE | Nitric oxide synthase | 3 | 3 |
Molecules with ChEMBL bioactivity
Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,049,502 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).
10 molecules by phase:
| Molecule | Name | Phase | Patents |
|---|---|---|---|
| CHEMBL1371 | CHLORZOXAZONE | 4 | 16,875 |
| CHEMBL1485 | ARGININE | 3 | 905,111 |
| CHEMBL140 | CURCUMIN | 3 | 95,185 |
| CHEMBL256147 | TILARGININE | 3 | 2,046 |
| CHEMBL114551 | GW-274150 | 2 | 1,071 |
| CHEMBL1911882 | KD7040 | 2 | 8 |
| CHEMBL1093059 | BARDOXOLONE | 2 | 944 |
| CHEMBL7890 | L-NAME | 2 | 1,196 |
| CHEMBL225304 | PIMAGEDINE | 2 | 24,594 |
| CHEMBL227744 | NITROARGININE | 1 | 2,472 |
PharmGKB: 1 entry (CPIC guideline: no)
GtoPdb / IUPHAR curated pharmacology
(IUPHAR/BPS Guide to Pharmacology — expert-curated)
Target class: enzyme — Nitric oxide synthases
Most potent curated ligand interactions (7 total), top 7:
| Ligand | Action | Affinity | Parameter |
|---|---|---|---|
| 1400W | Inhibition | 8.2 | pIC50 |
| 2-amino-4-methylpyridine | Inhibition | 7.4 | pIC50 |
| PIBTU | Inhibition | 7.3 | pIC50 |
| GW274150 | Inhibition | 7.15 | pIC50 |
| L-NNA | Inhibition | 6.17 | pKi |
| tilarginine | Inhibition | 6.07 | pKi |
| NIL | Inhibition | 5.5 | pIC50 |
Binding affinities (BindingDB)
953 measured of 1094 human assays (1178 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.
| Ligand | Measure | Value | Patent |
|---|---|---|---|
| 2-((R)-1-(2-(1H-imidazol-1-yl)-6-methylpyrimidin-4-yl)pyrrolidin-2-yl)-N-(benzo[d][1,3]dioxol-5-ylmethyl)acetamide | IC50 | 0.12 nM | |
| 2-((R)-1-(2-(1H-imidazol-1-yl)-6-methylpyrimidin-4-yl)pyrrolidin-2-yl)-N-(benzo[d][1,3]dioxol-5-ylmethyl)acetamide | IC50 | 0.13 nM | |
| methyl (3S)-3-{2-[(1,3-benzodioxol-5-ylmethyl)amino]-2-oxoethyl}-4-[2-(1H-imidazol-1-yl)pyrimidin-4-yl]piperazine-1-carboxylate | IC50 | 0.24 nM | |
| N-[(1,3-benzodioxol-5-yl)methyl]-1-[2-(1H-imidazol-1-yl)pyrimidin-4-yl]-4-(6-fluoropyridin-2-yl)-2-piperazineacetamide | IC50 | 0.28 nM | |
| 2-((R)-1-(2-(1H-imidazol-1-yl)pyrimidin-4-yl)pyrrolidin-2-yl)-N-(benzo[d][1,3]dioxol-5-ylmethyl)acetamide | IC50 | 0.28 nM | |
| N-[2-(1,3-BENZODIOXOL-5-YL)ETHYL]-1-[2-(1H-IMIDAZOL-1-YL)-6-METHYLPYRIMIDIN-4-YL]-D-PROLINAMIDE | IC50 | 0.29 nM | |
| 3-{[(Benzo[1,3]dioxol-5-ylmethyl)-carbamoyl]-methyl}-4-(2-imidazol-1-yl-pyrimidin-4-yl)-piperazine-1-carboxylic acid methyl ester | IC50 | 0.38 nM | |
| 2-((R)-1-(2-(1H-imidazol-1-yl)-6-methylpyrimidin-4-yl)pyrrolidin-2-yl)-N-(benzo[d][1,3]dioxol-5-ylmethyl)acetamide | IC50 | 0.48 nM | |
| N-[(1,3-benzodioxol-5-yl)methyl]-1-[2-(1H-imidazol-1-yl)pyrimidin-4-yl]-4-methyl-2-piperazineacetamide | IC50 | 0.48 nM | |
| N-(1,3-benzodioxol-5-ylmethyl)-1-[6-chloro-2-(1H-imidazol-1-yl)-4-pyrimidinyl]-2-piperidineacetamide | IC50 | 0.49 nM | |
| N-[(1,3-benzodioxol-5-yl)methyl]-1-[2-(1H-imidazol-1-yl)pyrimidin-4-yl]-4-(methylsulfonyl)-2-piperazineacetamide | IC50 | 0.5 nM | |
| N-[(1,3-benzodioxol-5-yl)methyl]-1-[2-(1H-imidazol-1-yl)-4-pyrimidinyl]-2-piperidineacetamide | IC50 | 0.5 nM | |
| N-[(1,3-benzodioxol-5-yl)methyl]-1-[2-(1H-imidazol-1-yl)pyrimidin-4-yl]-4-(phenylcarbonyl)-2-piperazineacetamide | IC50 | 0.5 nM | |
| N-[(1,3-benzodioxol-5-yl)methyl]-4-[2-(1H-imidazol-1-yl)-4-pyrimidinyl]-3-morpholineacetamide | IC50 | 0.5 nM | |
| (2R)-N-(2-(benzo[d][1,3]dioxol-5-yl)ethyl)-1-(6-ethyl-2-(1H-imidazol-1-yl)pyrimidin-4-yl)pyrrolidine-2-carboxamide | IC50 | 0.52 nM | |
| N-[(1,3-benzodioxol-5-yl)methyl]-1-[2-(1H-imidazol-1-yl)pyrimidin-4-yl]-2-piperazineacetamide | IC50 | 0.55 nM | |
| N-[(1,3-benzodioxol-5-yl)methyl]-1-[2-(1H-imidazol-1-yl)pyrimidin-4-yl]-4-(2-furylmethyl)-2-piperazineacetamide | IC50 | 0.58 nM | |
| N-(1,3-benzodioxol-5-ylmethyl)-4-(2-furanylcarbonyl)-1-[2-(1H-imidazolyl)-4-pyrimidinyl]-2-piperazineacetamide | IC50 | 0.67 nM | |
| N-[(1,3-benzodioxol-5-yl)methyl]-1-[2-(1H-imidazol-1-yl)pyrimidin-4-yl]-4-(methylsulfonyl)-2-piperazineacetamide | IC50 | 0.7 nM | |
| 2-((R)-4-(2-(1H-imidazol-1-yl)-6-methylpyrimidin-4-yl)-1-isobutyrylpiperazin-2-yl)-N-(benzo[d][1,3]dioxol-5-ylmethyl)acetamide | IC50 | 0.75 nM | |
| 1-[2-(1H-imidazol-1-yl)-4-pyrimidinyl]-N-[(4-methoxyphenyl-)methyl]-2-piperidineacetamide | IC50 | 0.8 nM | |
| N-[(1,3-benzodioxol-5-yl)methyl]-1-[2-(1H-imidazol-1-yl)pyrimidin-4-yl]-4-[(phenylmethoxy)carbonyl]piperazine-2-acetamide | IC50 | 0.8 nM | |
| N-(1,3-benzodioxol-5-ylmethyl)-1-[2-(1H-imidazol-yl)-4-pyrimidinyl]-4-(phenylamino)carbonyl]-2-piperazineacetamide | IC50 | 0.87 nM | |
| N-[(1,3-benzodioxol-5-yl)methyl]-1-[2-(1H-imidazol-1-yl)pyrimidin-4-yl]-4-(2-furylmethyl)-2-piperazineacetamide | IC50 | 0.93 nM | |
| N-(1,3-benzodioxol-5-ylmethyl)-1-[2-(1H-imidazol-yl)-4-pyrimidinyl]-4-[[(phenylmethyl)amino]carbonyl]-2-piperazineacetamide | IC50 | 0.96 nM | |
| N-[(1,3-benzodioxol-5-yl)methyl]-1-[2-(1H-imidazol-1-yl)pyrimidin-4-yl]-4-(phenylmethyl)-2-piperazineacetamide | IC50 | 1 nM | |
| 3-[2-[(1,3-benzodioxol-5-ylmethyl)amino]-2-oxoethyl]-4-[2-(1H-imidazolyl)-4-pyrimidinyl]-1-piperazinecarboxylic Acid, 1-methyl ethyl ester | IC50 | 1 nM | |
| N-[(1,3-benzodioxol-5-yl)methyl]-1-[2-(1H-imidazol-1-yl)pyrimidin-4-yl]-4-[(methylamino)carbonyl]-2-piperazineacetamide | IC50 | 1 nM | |
| 4-(acetyl)-N-[(1,3-benzodioxol-5-yl)methyl]-1-[2-(1H-imidazol-1-yl)pyrimidin-4-yl]-2-piperazineacetamide | IC50 | 1 nM | |
| N-[(1,3-benzodioxol-5-yl)methyl]-1-[2-(1H-imidazol-1-yl)pyrimidin-4-yl]-4-(3-methylbutyl)-2-piperazineacetamide | IC50 | 1 nM | |
| CHEMBL106871 | IC50 | 1 nM | |
| N-Benzo[1,3]dioxol-5-ylmethyl-2-[1-(6-chloro-2-imidazol-1-yl-pyrimidin-4-yl)-piperazin-2-yl]-acetamide | IC50 | 1.1 nM | |
| N-[(1,3-benzodioxol-5-yl)methyl]-4-[(5-dimethylaminonaphthyl)sulfonyl]-1-[2-(1H-imidazol-1-yl)pyrimidin-4-yl]-2-piperazineacetamide | IC50 | 1.1 nM | |
| 3-[2-[(1,3-benzodioxol-5-ylmethyl)amino]-2-oxoethyl]-4-[2-(1H-imidazolyl)-4-pyrimidinyl]-1-piperazinecarboxylic acid, phenyl ester | IC50 | 1.4 nM | |
| 1-[2-(1H-imidazol-1-yl)pyrimidin-4-yl]-N-[(3,4-dimethoxyphenyl)methyl]-2-piperidineacetamide | IC50 | 1.5 nM | |
| N-[(1,3-benzodioxol-5-yl)methyl]-4-[2-(1H-imidazol-1-yl)-6-methylpyrimidin-4-yl]-1-[(1-methylethyl)carbonyl]-2-piperazineacetamide | IC50 | 1.9 nM | |
| 8a-(imidazole-1-carbonyl)-4,4,6a,6b,11,11,14b-heptamethyl-3,13-dioxo-4a,5,6,6a,7,8,9,10,12,12a-decahydropicene-2-carbonitrile | IC50 | 2 nM | US-10189791: Pyridyl analogs of 1-(2-cyano-3,12-dioxooleana-1,9(11)dien-28-oyl) imidazole |
| N-[(1,3-benzodioxol-5-yl)methyl]hexahydro-1-[2-(1H-imidazol-1-yl)-4-pyrimidinyl]-1H-azepine-2-acetamide | IC50 | 2 nM | |
| N-(1,3-benzodioxol-5-ylmethyl)-1-[2-(1H-imidazol-yl)-4-pyrimidinyl]-4-(phenylsulfonyl)-2-piperazineacetamide | IC50 | 2.7 nM | |
| N-[(4-fluorophenyl)methyl]-1-[2-(1H-imidazol-1-yl)pyrimidin-4-yl]-2-piperidineacetamide | IC50 | 3 nM | |
| 1-[2-(1H-imidazol-1-yl)-4-pyrimidinyl]-N-[2-(4-methoxyphenyl)ethyl]-2-piperidineacetamide | IC50 | 3.5 nM | |
| 1-[2-(1H-imidazol-1-yl)pyrimidin-4-yl]-N-[(3-methoxyphenyl-)methyl]-2-piperidineacetamide | IC50 | 3.7 nM | |
| N-(1,3-benzodioxol-5-ylmethyl)-1-[2-(1H-imidazol-1-yl)-6-methyl-4-pyrimidinyl]-2-piperidineacetamide | IC50 | 4.1 nM | |
| 4,4,6a,6b,11,11,14b-heptamethyl-3,13-dioxo-8a-(4-pyridin-3-ylimidazole-1-carbonyl)-4a,5,6,6a,7,8,9,10,12,12a-decahydropicene-2-carbonitrile | IC50 | 4.3 nM | US-10189791: Pyridyl analogs of 1-(2-cyano-3,12-dioxooleana-1,9(11)dien-28-oyl) imidazole |
| 2-[2-[(1,3-benzodioxol-5-ylmethyl)amino]-2-oxoethyl]-4-[2-(1H-imidazol-1-yl)-6-methyl-4-pyrimidinyl]-1-piperazinecarboxylic acid, methyl ester | IC50 | 5.4 nM | |
| N-[(4-chlorophenyl)methyl]-1-[2-(1H-imidazol-1-yl)pyrimidin-4-yl]-2-piperidineacetamide | IC50 | 5.7 nM | |
| 4,4,6a,6b,11,11,14b-heptamethyl-3,13-dioxo-8a-(4-pyridin-2-ylimidazole-1-carbonyl)-4a,5,6,6a,7,8,9,10,12,12a-decahydropicene-2-carbonitrile | IC50 | 5.8 nM | US-10189791: Pyridyl analogs of 1-(2-cyano-3,12-dioxooleana-1,9(11)dien-28-oyl) imidazole |
| N-(3-Aminomethyl-phenyl)-furan-2-carboxamidine | KI | 6 nM | |
| N-(3-Aminomethyl-phenyl)-furan-2-carboxamidine | KI | 6.3 nM | |
| N-[(1,3-benzodioxol-5-yl)methyl]-4-[2-(1H-imidazol-1-yl)-6-methylpyrimidin-4-yl]-1-(methylcarbonyl)-2-piperazineacetamide | IC50 | 8.5 nM |
ChEMBL bioactivities
966 potent at pChembl≥5 of 1253 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).
| pChembl | Type | Value | Unit | Molecule |
|---|---|---|---|---|
| 9.92 | IC50 | 0.12 | nM | CHEMBL220632 |
| 9.89 | IC50 | 0.13 | nM | CHEMBL220880 |
| 9.70 | IC50 | 0.2 | nM | BARDOXOLONE |
| 9.62 | IC50 | 0.24 | nM | CHEMBL385324 |
| 9.55 | IC50 | 0.28 | nM | CHEMBL385325 |
| 9.55 | IC50 | 0.28 | nM | CHEMBL376733 |
| 9.54 | IC50 | 0.29 | nM | CHEMBL376632 |
| 9.42 | IC50 | 0.38 | nM | CHEMBL290548 |
| 9.32 | IC50 | 0.48 | nM | CHEMBL373623 |
| 9.32 | IC50 | 0.48 | nM | CHEMBL427062 |
| 9.31 | IC50 | 0.49 | nM | CHEMBL223788 |
| 9.30 | IC50 | 0.5 | nM | CHEMBL376713 |
| 9.30 | IC50 | 0.5 | nM | CHEMBL385334 |
| 9.30 | IC50 | 0.5 | nM | CHEMBL220932 |
| 9.30 | IC50 | 0.5 | nM | CHEMBL442041 |
| 9.28 | IC50 | 0.52 | nM | CHEMBL221208 |
| 9.26 | IC50 | 0.55 | nM | CHEMBL411343 |
| 9.24 | IC50 | 0.58 | nM | CHEMBL424928 |
| 9.22 | IC50 | 0.6 | nM | CHEMBL290548 |
| 9.17 | IC50 | 0.67 | nM | CHEMBL223782 |
| 9.15 | IC50 | 0.7 | nM | CHEMBL373881 |
| 9.12 | IC50 | 0.75 | nM | CHEMBL222362 |
| 9.10 | IC50 | 0.8 | nM | CHEMBL223792 |
| 9.10 | IC50 | 0.8 | nM | CHEMBL374681 |
| 9.06 | IC50 | 0.87 | nM | CHEMBL374319 |
| 9.03 | IC50 | 0.93 | nM | CHEMBL222364 |
| 9.02 | IC50 | 0.96 | nM | CHEMBL223791 |
| 9.00 | IC50 | 1 | nM | CHEMBL374132 |
| 9.00 | IC50 | 1 | nM | CHEMBL220834 |
| 9.00 | IC50 | 1 | nM | CHEMBL375404 |
| 9.00 | IC50 | 1 | nM | CHEMBL223384 |
| 9.00 | IC50 | 1 | nM | CHEMBL223634 |
| 8.96 | IC50 | 1.1 | nM | CHEMBL440473 |
| 8.96 | IC50 | 1.1 | nM | CHEMBL223838 |
| 8.85 | IC50 | 1.4 | nM | CHEMBL223385 |
| 8.82 | IC50 | 1.5 | nM | CHEMBL220121 |
| 8.74 | Ki | 1.8 | nM | CHEMBL1800346 |
| 8.74 | IC50 | 1.8 | nM | TILARGININE |
| 8.73 | Ki | 1.862 | nM | CHEMBL1800346 |
| 8.72 | IC50 | 1.9 | nM | CHEMBL220771 |
| 8.70 | IC50 | 2 | nM | CHEMBL223442 |
| 8.70 | EC50 | 2 | nM | CHEMBL489724 |
| 8.70 | Ki | 2 | nM | CHEMBL105792 |
| 8.70 | IC50 | 2 | nM | CHEMBL5947337 |
| 8.70 | IC50 | 2 | nM | CHEMBL354788 |
| 8.66 | Ki | 2.2 | nM | CHEMBL290548 |
| 8.57 | IC50 | 2.7 | nM | CHEMBL220156 |
| 8.52 | IC50 | 3 | nM | CHEMBL436535 |
| 8.52 | EC50 | 3 | nM | CHEMBL491923 |
| 8.52 | EC50 | 3 | nM | CHEMBL492090 |
PubChem BioAssay actives
865 with measured affinity, of 1588 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 |
|---|---|---|---|---|
| N-(1,3-benzodioxol-5-ylmethyl)-2-[(2R)-1-(6-ethyl-2-imidazol-1-ylpyrimidin-4-yl)pyrrolidin-2-yl]acetamide | 280474: Inhibition of cytokine-induced iNOS expressed in human A172 cells assessed as inhibition of NO formation | ic50 | 0.0001 | uM |
| N-(1,3-benzodioxol-5-ylmethyl)-2-[(2R)-1-(2-imidazol-1-yl-6-methylpyrimidin-4-yl)pyrrolidin-2-yl]acetamide | 280474: Inhibition of cytokine-induced iNOS expressed in human A172 cells assessed as inhibition of NO formation | ic50 | 0.0001 | uM |
| methyl (3S)-3-[2-(1,3-benzodioxol-5-ylmethylamino)-2-oxoethyl]-4-(2-imidazol-1-ylpyrimidin-4-yl)piperazine-1-carboxylate | 280474: Inhibition of cytokine-induced iNOS expressed in human A172 cells assessed as inhibition of NO formation | ic50 | 0.0002 | uM |
| (4aS,6aR,6bS,8aR,12aS,14aR,14bS)-11-cyano-2,2,6a,6b,9,9,12a-heptamethyl-10,14-dioxo-1,3,4,5,6,7,8,8a,14a,14b-decahydropicene-4a-carboxylic acid | 241425: Inhibition of inducible nitric oxide synthase in activated macrophages | ic50 | 0.0002 | uM |
| N-(1,3-benzodioxol-5-ylmethyl)-2-[4-(6-fluoro-2-pyridinyl)-1-(2-imidazol-1-ylpyrimidin-4-yl)piperazin-2-yl]acetamide | 280474: Inhibition of cytokine-induced iNOS expressed in human A172 cells assessed as inhibition of NO formation | ic50 | 0.0003 | uM |
| N-(1,3-benzodioxol-5-ylmethyl)-2-[(2R)-1-(2-imidazol-1-ylpyrimidin-4-yl)pyrrolidin-2-yl]acetamide | 280474: Inhibition of cytokine-induced iNOS expressed in human A172 cells assessed as inhibition of NO formation | ic50 | 0.0003 | uM |
| (2R)-N-[2-(1,3-benzodioxol-5-yl)ethyl]-1-(2-imidazol-1-yl-6-methylpyrimidin-4-yl)pyrrolidine-2-carboxamide | 280474: Inhibition of cytokine-induced iNOS expressed in human A172 cells assessed as inhibition of NO formation | ic50 | 0.0003 | uM |
| methyl 3-[2-(1,3-benzodioxol-5-ylmethylamino)-2-oxoethyl]-4-(2-imidazol-1-ylpyrimidin-4-yl)piperazine-1-carboxylate | 280474: Inhibition of cytokine-induced iNOS expressed in human A172 cells assessed as inhibition of NO formation | ic50 | 0.0004 | uM |
| N-(1,3-benzodioxol-5-ylmethyl)-2-[4-benzoyl-1-(2-imidazol-1-ylpyrimidin-4-yl)piperazin-2-yl]acetamide | 280474: Inhibition of cytokine-induced iNOS expressed in human A172 cells assessed as inhibition of NO formation | ic50 | 0.0005 | uM |
| N-(1,3-benzodioxol-5-ylmethyl)-2-[1-(2-imidazol-1-ylpyrimidin-4-yl)-4-(2-phenylmethoxyacetyl)piperazin-2-yl]acetamide | 280474: Inhibition of cytokine-induced iNOS expressed in human A172 cells assessed as inhibition of NO formation | ic50 | 0.0005 | uM |
| N-(1,3-benzodioxol-5-ylmethyl)-2-[1-(6-chloro-2-imidazol-1-ylpyrimidin-4-yl)piperidin-2-yl]acetamide | 280474: Inhibition of cytokine-induced iNOS expressed in human A172 cells assessed as inhibition of NO formation | ic50 | 0.0005 | uM |
| (2R)-N-[2-(1,3-benzodioxol-5-yl)ethyl]-1-(6-ethyl-2-imidazol-1-ylpyrimidin-4-yl)pyrrolidine-2-carboxamide | 280474: Inhibition of cytokine-induced iNOS expressed in human A172 cells assessed as inhibition of NO formation | ic50 | 0.0005 | uM |
| N-(1,3-benzodioxol-5-ylmethyl)-2-[4-(2-imidazol-1-ylpyrimidin-4-yl)morpholin-3-yl]acetamide | 280474: Inhibition of cytokine-induced iNOS expressed in human A172 cells assessed as inhibition of NO formation | ic50 | 0.0005 | uM |
| N-(1,3-benzodioxol-5-ylmethyl)-2-[1-(2-imidazol-1-ylpyrimidin-4-yl)-4-methylpiperazin-2-yl]acetamide | 280474: Inhibition of cytokine-induced iNOS expressed in human A172 cells assessed as inhibition of NO formation | ic50 | 0.0005 | uM |
| N-(1,3-benzodioxol-5-ylmethyl)-2-[1-(2-imidazol-1-ylpyrimidin-4-yl)piperidin-2-yl]acetamide | 280474: Inhibition of cytokine-induced iNOS expressed in human A172 cells assessed as inhibition of NO formation | ic50 | 0.0005 | uM |
| (2R)-N-[2-(1,3-benzodioxol-5-yl)ethyl]-1-(2-imidazol-1-ylpyrimidin-4-yl)pyrrolidine-2-carboxamide | 280474: Inhibition of cytokine-induced iNOS expressed in human A172 cells assessed as inhibition of NO formation | ic50 | 0.0005 | uM |
| N-(1,3-benzodioxol-5-ylmethyl)-2-[1-(2-imidazol-1-ylpyrimidin-4-yl)piperazin-2-yl]acetamide | 280474: Inhibition of cytokine-induced iNOS expressed in human A172 cells assessed as inhibition of NO formation | ic50 | 0.0006 | uM |
| N-(1,3-benzodioxol-5-ylmethyl)-2-[4-(furan-2-ylmethyl)-1-(2-imidazol-1-ylpyrimidin-4-yl)piperazin-2-yl]acetamide | 280474: Inhibition of cytokine-induced iNOS expressed in human A172 cells assessed as inhibition of NO formation | ic50 | 0.0006 | uM |
| N-(1,3-benzodioxol-5-ylmethyl)-2-[1-(2-imidazol-1-ylpyrimidin-4-yl)-4-methylsulfonylpiperazin-2-yl]acetamide | 280474: Inhibition of cytokine-induced iNOS expressed in human A172 cells assessed as inhibition of NO formation | ic50 | 0.0007 | uM |
| N-(1,3-benzodioxol-5-ylmethyl)-2-[4-(furan-2-carbonyl)-1-(2-imidazol-1-ylpyrimidin-4-yl)piperazin-2-yl]acetamide | 280474: Inhibition of cytokine-induced iNOS expressed in human A172 cells assessed as inhibition of NO formation | ic50 | 0.0007 | uM |
| 2-[1-(2-imidazol-1-ylpyrimidin-4-yl)piperidin-2-yl]-N-[(4-methoxyphenyl)methyl]acetamide | 280474: Inhibition of cytokine-induced iNOS expressed in human A172 cells assessed as inhibition of NO formation | ic50 | 0.0008 | uM |
| N-(1,3-benzodioxol-5-ylmethyl)-2-[(2R)-4-(2-imidazol-1-yl-6-methylpyrimidin-4-yl)-1-(2-methylpropanoyl)piperazin-2-yl]acetamide | 280474: Inhibition of cytokine-induced iNOS expressed in human A172 cells assessed as inhibition of NO formation | ic50 | 0.0008 | uM |
| benzyl 3-[2-(1,3-benzodioxol-5-ylmethylamino)-2-oxoethyl]-4-(2-imidazol-1-ylpyrimidin-4-yl)piperazine-1-carboxylate | 280474: Inhibition of cytokine-induced iNOS expressed in human A172 cells assessed as inhibition of NO formation | ic50 | 0.0008 | uM |
| ethyl 2-[3-[2-(1,3-benzodioxol-5-ylmethylamino)-2-oxoethyl]-4-(2-imidazol-1-ylpyrimidin-4-yl)piperazin-1-yl]acetate | 280474: Inhibition of cytokine-induced iNOS expressed in human A172 cells assessed as inhibition of NO formation | ic50 | 0.0009 | uM |
| 3-[2-(1,3-benzodioxol-5-ylmethylamino)-2-oxoethyl]-4-(2-imidazol-1-ylpyrimidin-4-yl)-N-phenylpiperazine-1-carboxamide | 280474: Inhibition of cytokine-induced iNOS expressed in human A172 cells assessed as inhibition of NO formation | ic50 | 0.0009 | uM |
| N-(1,3-benzodioxol-5-ylmethyl)-2-[4-benzyl-1-(2-imidazol-1-ylpyrimidin-4-yl)piperazin-2-yl]acetamide | 280474: Inhibition of cytokine-induced iNOS expressed in human A172 cells assessed as inhibition of NO formation | ic50 | 0.0010 | uM |
| 3-[2-(1,3-benzodioxol-5-ylmethylamino)-2-oxoethyl]-4-(2-imidazol-1-ylpyrimidin-4-yl)-N-methylpiperazine-1-carboxamide | 280474: Inhibition of cytokine-induced iNOS expressed in human A172 cells assessed as inhibition of NO formation | ic50 | 0.0010 | uM |
| 3-[2-(1,3-benzodioxol-5-ylmethylamino)-2-oxoethyl]-N-benzyl-4-(2-imidazol-1-ylpyrimidin-4-yl)piperazine-1-carboxamide | 280474: Inhibition of cytokine-induced iNOS expressed in human A172 cells assessed as inhibition of NO formation | ic50 | 0.0010 | uM |
| N-(1,3-benzodioxol-5-ylmethyl)-2-[1-(2-imidazol-1-ylpyrimidin-4-yl)-4-(3-methylbutyl)piperazin-2-yl]acetamide | 280474: Inhibition of cytokine-induced iNOS expressed in human A172 cells assessed as inhibition of NO formation | ic50 | 0.0010 | uM |
| 2-[4-acetyl-1-(2-imidazol-1-ylpyrimidin-4-yl)piperazin-2-yl]-N-(1,3-benzodioxol-5-ylmethyl)acetamide | 280474: Inhibition of cytokine-induced iNOS expressed in human A172 cells assessed as inhibition of NO formation | ic50 | 0.0010 | uM |
| propan-2-yl 3-[2-(1,3-benzodioxol-5-ylmethylamino)-2-oxoethyl]-4-(2-imidazol-1-ylpyrimidin-4-yl)piperazine-1-carboxylate | 280474: Inhibition of cytokine-induced iNOS expressed in human A172 cells assessed as inhibition of NO formation | ic50 | 0.0010 | uM |
| N-(1,3-benzodioxol-5-ylmethyl)-2-[4-[5-(dimethylamino)naphthalen-1-yl]sulfonyl-1-(2-imidazol-1-ylpyrimidin-4-yl)piperazin-2-yl]acetamide | 280474: Inhibition of cytokine-induced iNOS expressed in human A172 cells assessed as inhibition of NO formation | ic50 | 0.0011 | uM |
| N-(1,3-benzodioxol-5-ylmethyl)-2-[1-(6-chloro-2-imidazol-1-ylpyrimidin-4-yl)piperazin-2-yl]acetamide | 92002: Inhibitory activity against the partially purified human Inducible nitric oxide synthase | ic50 | 0.0011 | uM |
| phenyl 3-[2-(1,3-benzodioxol-5-ylmethylamino)-2-oxoethyl]-4-(2-imidazol-1-ylpyrimidin-4-yl)piperazine-1-carboxylate | 280474: Inhibition of cytokine-induced iNOS expressed in human A172 cells assessed as inhibition of NO formation | ic50 | 0.0014 | uM |
| N-[(3,4-dimethoxyphenyl)methyl]-2-[1-(2-imidazol-1-ylpyrimidin-4-yl)piperidin-2-yl]acetamide | 280474: Inhibition of cytokine-induced iNOS expressed in human A172 cells assessed as inhibition of NO formation | ic50 | 0.0015 | uM |
| (2S)-2-amino-5-[(N’-methylcarbamimidoyl)amino]pentanoic acid | 669683: Inhibition of human recombinant iNOS assessed as conversion of [3H]L-arginine to [3H]L-citrulline preincubated for 15 mins measured after 45 mins by liquid scintillation counting | ic50 | 0.0018 | uM |
| (1S,5S,6R,7R)-7-chloro-5-methyl-2-azabicyclo[4.1.0]hept-2-en-3-amine;hydrochloride | 667551: Inhibition of human iNOS | ki | 0.0018 | uM |
| N-(1,3-benzodioxol-5-ylmethyl)-2-[4-(2-imidazol-1-yl-6-methylpyrimidin-4-yl)-1-(2-methylpropanoyl)piperazin-2-yl]acetamide | 280474: Inhibition of cytokine-induced iNOS expressed in human A172 cells assessed as inhibition of NO formation | ic50 | 0.0019 | uM |
| 5,8-difluoro-2-(furan-2-yl)-1,2-dihydroquinazolin-4-amine | 92004: Inhibitory activity of compound against human inducible nitric oxide synthase | ic50 | 0.0020 | uM |
| N-(1,3-benzodioxol-5-ylmethyl)-2-[1-(2-imidazol-1-ylpyrimidin-4-yl)azepan-2-yl]acetamide | 280474: Inhibition of cytokine-induced iNOS expressed in human A172 cells assessed as inhibition of NO formation | ic50 | 0.0020 | uM |
| N-(3-chlorophenyl)-N-[(7,8-difluoro-2-oxo-1H-quinolin-4-yl)methyl]-4-methyl-1,3-thiazole-5-carboxamide | 349841: Inhibition of human iNOS expressed in HEK293 cells assessed as NO production by transient transfection assay | ec50 | 0.0020 | uM |
| (1S,5S,6R,7R)-7-chloro-5-methyl-2-azabicyclo[4.1.0]hept-2-en-3-amine | 2007178: Inhibition of human iNOS overexpressed in baculovirus infected Sf21 cells assessed as inhibition constant | ki | 0.0020 | uM |
| 2-[4-(benzenesulfonyl)-1-(2-imidazol-1-ylpyrimidin-4-yl)piperazin-2-yl]-N-(1,3-benzodioxol-5-ylmethyl)acetamide | 280474: Inhibition of cytokine-induced iNOS expressed in human A172 cells assessed as inhibition of NO formation | ic50 | 0.0027 | uM |
| N-[(4-fluorophenyl)methyl]-2-[1-(2-imidazol-1-ylpyrimidin-4-yl)piperidin-2-yl]acetamide | 280474: Inhibition of cytokine-induced iNOS expressed in human A172 cells assessed as inhibition of NO formation | ic50 | 0.0030 | uM |
| N-(3-chlorophenyl)-N-[(7,8-difluoro-2-oxo-1H-quinolin-4-yl)methyl]-3-methylimidazole-4-carboxamide | 349841: Inhibition of human iNOS expressed in HEK293 cells assessed as NO production by transient transfection assay | ec50 | 0.0030 | uM |
| N-(3-chlorophenyl)-N-[(7,8-difluoro-2-oxo-1H-quinolin-4-yl)methyl]-3,5-dimethyl-1,2-oxazole-4-carboxamide | 349841: Inhibition of human iNOS expressed in HEK293 cells assessed as NO production by transient transfection assay | ec50 | 0.0030 | uM |
| 2-[1-(2-imidazol-1-ylpyrimidin-4-yl)piperidin-2-yl]-N-[2-(4-methoxyphenyl)ethyl]acetamide | 280474: Inhibition of cytokine-induced iNOS expressed in human A172 cells assessed as inhibition of NO formation | ic50 | 0.0035 | uM |
| 2-[1-(2-imidazol-1-ylpyrimidin-4-yl)piperidin-2-yl]-N-[(3-methoxyphenyl)methyl]acetamide | 280474: Inhibition of cytokine-induced iNOS expressed in human A172 cells assessed as inhibition of NO formation | ic50 | 0.0037 | uM |
| N-(1,3-benzodioxol-5-ylmethyl)-2-[2-(2-imidazol-1-yl-6-methylpyrimidin-4-yl)pyrrolidin-1-yl]-N-methylethanamine | 626385: Inhibition of human iNOS expressed in human HEK293 cells assessed as nitrite accumulation after 18 hrs by 2,3-diaminonapthalene assay | ec50 | 0.0040 | uM |
| 2-[(1R)-3-amino-1-phenylpropyl]sulfanyl-6-methylpyridine-3-carbonitrile;(E)-but-2-enedioic acid | 589858: Inhibition of human recombinant iNOS | ic50 | 0.0040 | uM |
CTD chemical–gene interactions
336 total (human), top 30 by PubMed support.
| Chemical | Actions (top 5) | PubMed papers |
|---|---|---|
| Lipopolysaccharides | increases chemical synthesis, increases activity, affects cotreatment, decreases expression, increases expression (+5 more) | 28 |
| Nitric Oxide | decreases reaction, increases chemical synthesis, decreases expression, affects cotreatment, decreases methylation (+10 more) | 24 |
| Resveratrol | decreases stability, decreases expression, decreases abundance, affects cotreatment, decreases reaction (+4 more) | 8 |
| Benzo(a)pyrene | affects methylation, affects expression, affects reaction, decreases expression, decreases reaction (+2 more) | 7 |
| Quercetin | decreases reaction, increases expression, affects cotreatment, decreases expression | 7 |
| Particulate Matter | affects methylation, decreases methylation, increases expression, affects response to substance, increases abundance | 7 |
| Plant Extracts | decreases reaction, increases expression, decreases chemical synthesis, increases reaction, decreases expression (+1 more) | 6 |
| pyrrolidine dithiocarbamic acid | increases expression, affects cotreatment, decreases reaction | 5 |
| Air Pollutants | increases expression, affects response to substance, affects abundance, decreases reaction, affects methylation (+2 more) | 5 |
| Glucose | decreases reaction, affects expression, increases expression, affects reaction | 5 |
| Tetradecanoylphorbol Acetate | increases reaction, decreases reaction, increases expression, affects cotreatment | 5 |
| Valproic Acid | affects cotreatment, decreases expression, increases expression | 5 |
| Cadmium | increases abundance, increases expression, increases secretion, decreases reaction | 4 |
| Cadmium Chloride | affects cotreatment, decreases reaction, increases activity, increases abundance, increases expression | 4 |
| bisphenol A | increases expression, decreases reaction | 3 |
| arsenite | increases activity, increases expression | 3 |
| sodium arsenite | decreases expression, increases expression | 3 |
| 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one | increases expression, increases reaction, affects cotreatment, decreases expression, decreases reaction | 3 |
| SB 203580 | affects cotreatment, decreases reaction, increases expression | 3 |
| U 0126 | decreases expression, decreases reaction, increases expression | 3 |
| Acetylcysteine | affects cotreatment, decreases expression, decreases reaction, increases expression | 3 |
| Curcumin | decreases reaction, increases expression, increases activity | 3 |
| Cycloheximide | decreases reaction, increases expression, affects cotreatment | 3 |
| Doxorubicin | decreases expression, increases expression, increases reaction | 3 |
| Chlorpyrifos | increases expression | 3 |
| Glucosamine | increases reaction, affects cotreatment, decreases expression, decreases reaction, increases expression | 3 |
| Melitten | decreases reaction, increases chemical synthesis, increases expression, decreases expression | 3 |
| Methotrexate | decreases reaction, increases chemical synthesis, increases expression | 3 |
| Mustard Gas | increases expression, decreases reaction, decreases expression | 3 |
| Nitroprusside | decreases reaction, increases chemical synthesis, increases expression, affects cotreatment, decreases activity | 3 |
ChEMBL screening assays
263 unique, capped per target: 255 binding, 5 functional, 2 admet, 1 unclassified
Representative assays (with source publication via chembl_document):
| Assay ID | Type | Description | Source paper |
|---|---|---|---|
| CHEMBL1003684 | Binding | Selectivity ratio, EC50 for human iNOS over EC50 for human nNOS | Discovery of inducible nitric oxide synthase (iNOS) inhibitor development candidate KD7332, part 1: Identification of a novel, potent, and selective series of quinolinone iNOS dimerization inhibitors that are orally active in rodent pain models. — *J Med Chem* |
| CHEMBL4346022 | Unclassified | Selectivity index, ratio of Ki for human iNOS expressed in Escherichia coli expression system to Ki for human nNOS expressed in Escherichia coli expression system | First Contact: 7-Phenyl-2-Aminoquinolines, Potent and Selective Neuronal Nitric Oxide Synthase Inhibitors That Target an Isoform-Specific Aspartate. — *J Med Chem* |
| CHEMBL4346021 | ADMET | Inhibition of human iNOS expressed in Escherichia coli expression system assessed as reduction in NO production in presence of L-arginine measured for 30 sec by hemoglobin capture assay | First Contact: 7-Phenyl-2-Aminoquinolines, Potent and Selective Neuronal Nitric Oxide Synthase Inhibitors That Target an Isoform-Specific Aspartate. — *J Med Chem* |
Cellosaurus cell lines
7 cell lines: 6 cancer cell line, 1 transformed cell line
First 10 cell lines (id-ordered, not curated):
| Cellosaurus | Name | Category | Sex |
|---|---|---|---|
| CVCL_B1YS | Abcam HeLa NOS2 KO | Cancer cell line | Female |
| CVCL_B7GG | 603B-iNOS antisense | Transformed cell line | Female |
| CVCL_B8LI | Abcam HCT 116 NOS2 KO | Cancer cell line | Male |
| CVCL_B8ZI | Abcam MCF-7 NOS2 KO | Cancer cell line | Female |
| CVCL_B9NN | Abcam A-549 NOS2 KO | Cancer cell line | Male |
| CVCL_TA85 | HAP1 NOS2 (-) 1 | Cancer cell line | Male |
| CVCL_TA86 | HAP1 NOS2 (-) 2 | Cancer cell line | Male |
Clinical trials (associated diseases)
Via MONDO — disease-level, not drug-specific.
showing 60 of 300 trials:
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT00000374 | Phase 4 | COMPLETED | Treatment for First-Episode Schizophrenia |
| NCT00001656 | Phase 4 | COMPLETED | Comparison of Clozapine vs Olanzapine in Childhood-Onset Psychotic Disorders |
| NCT00007774 | Phase 4 | COMPLETED | To Determine if Olanzapine is More Cost Effective Than Haloperidol for the Treatment of Schizophrenia |
| NCT00014001 | Phase 4 | COMPLETED | CATIE- Schizophrenia Trial |
| NCT00018668 | Phase 4 | COMPLETED | Antipsychotic Response in Schizophrenia |
| NCT00034801 | Phase 4 | COMPLETED | Olanzapine Versus Active Comparator in the Treatment of Depression in Patients With Schizophrenia |
| NCT00034905 | Phase 4 | COMPLETED | A Comparison of Seroquel vs. Risperidone in Schizophrenia |
| NCT00036088 | Phase 4 | COMPLETED | Olanzapine Versus An Active Comparator in the Treatment of Schizophrenia |
| NCT00044187 | Phase 4 | COMPLETED | The Assessment of a Weight-Gain Agent for the Treatment of Olanzapine-Associated Anti-Obesity Agent in Patients With Schizophrenia, Schizophreniform Disorder, Schizoaffective Disorder, and Bipolar I Disorder |
| NCT00044655 | Phase 4 | COMPLETED | Switching Medication to Treat Schizophrenia |
| NCT00048828 | Phase 4 | COMPLETED | Treating Drug-Resistant Childhood Schizophrenia |
| NCT00053703 | Phase 4 | COMPLETED | Treatment of Early Onset Schizophrenia Spectrum Disorders (TEOSS) |
| NCT00056498 | Phase 4 | COMPLETED | Risperidone Treatment in Schizophrenia Patients Who Are Currently Taking Clozapine |
| NCT00061802 | Phase 4 | COMPLETED | Efficacy and Safety of Two Atypical Antipsychotics vs. Placebo in Patients With an Acute Exacerbation of Either Schizophrenia or Schizoaffective Disorder |
| NCT00080327 | Phase 4 | COMPLETED | Study of Three Doses of Aripiprazole in Patients With Acute Schizophrenia |
| NCT00088049 | Phase 4 | COMPLETED | Study of Olanzapine vs. Aripiprazole in the Treatment of Schizophrenia |
| NCT00090012 | Phase 4 | COMPLETED | Comparison of Continuing Olanzapine to Switching to Quetiapine in Overweight or Obese Patients With Schizophrenia and Schizoaffective Disorder |
| NCT00100776 | Phase 4 | COMPLETED | Efficacy of High Dose Olanzapine for the Treatment of Schizophrenia and Schizoaffective Disorder |
| NCT00103571 | Phase 4 | COMPLETED | Olanzapine Versus Aripiprazole in the Treatment of Acutely Ill Patients With Schizophrenia |
| NCT00108368 | Phase 4 | COMPLETED | The Effects of Risperidone and Olanzapine on Thinking |
| NCT00114595 | Phase 4 | COMPLETED | Ethyl-Eicosapentaenoic Acid and Tardive Dyskinesia |
| NCT00130923 | Phase 4 | COMPLETED | Risperidone Long-acting Versus Oral Risperidone in Patients With Schizophrenia and Alcohol Use Disorder |
| NCT00137020 | Phase 4 | COMPLETED | Clinical Effect Of Cross Titration Of Antipsychotics With Ziprasidone In Schizophrenia Or Schizoaffective Disorder |
| NCT00140166 | Phase 4 | COMPLETED | Treatment of Acute Schizophrenia With Vitamin Therapy |
| NCT00145847 | Phase 4 | COMPLETED | Naltrexone Treatment of Alcohol Abuse in Schizophrenia |
| NCT00148564 | Phase 4 | COMPLETED | Energy Homeostasis Under Treatment With Atypical Antipsychotics |
| NCT00156715 | Phase 4 | COMPLETED | Efficacy of Quetiapine in the Treatment of Patients With Schizophrenia and a Comorbid Substance Use Disorder |
| NCT00158223 | Phase 4 | COMPLETED | Effectiveness of Pimozide in Augmenting the Effects of Clozapine in the Treatment of Schizophrenia |
| NCT00159081 | Phase 4 | COMPLETED | One Year Drug Treatment in First-Episode Schizophrenia |
| NCT00159120 | Phase 4 | COMPLETED | Maintenance Treatment vs. Stepwise Drug Discontinuation in First-Episode Schizophrenia |
| NCT00159133 | Phase 4 | COMPLETED | Prodrome-Based Early Intervention With Antipsychotics vs. Benzodiazepines in First-Episode Schizophrenia |
| NCT00159757 | Phase 4 | TERMINATED | 12 Week Open, Non-Comparative Switch Study Of Oral Ziprazidone In Previously Treated Schizophrenic Patients |
| NCT00167817 | Phase 4 | COMPLETED | Effect of Switch to Aripiprazole on Health and Smoking Parameters in Patients With Schizophrenia: A Pilot Study |
| NCT00169026 | Phase 4 | TERMINATED | Alcoholism and Schizophrenia: Effects of Clozapine |
| NCT00169039 | Phase 4 | TERMINATED | Clozapine Versus Chlorpromazine for Treatment-Unresponsive Schizophrenia |
| NCT00169065 | Phase 4 | COMPLETED | Effectiveness of Clozapine Versus Olanzapine for Treatment-resistant Schizophrenia |
| NCT00169091 | Phase 4 | TERMINATED | Clozapine Versus Haloperidol for Treating the First Episode of Schizophrenia |
| NCT00176423 | Phase 4 | COMPLETED | Efficacy Study of Galantamine for Cognitive Impairments in Schizophrenia |
| NCT00176436 | Phase 4 | COMPLETED | Atomoxetine for Treatment of Weight Gain in Olanzapine or Clozapine Patients |
| NCT00177008 | Phase 4 | COMPLETED | Aripiprazole for the Treatment of Schizophrenia With Co-Morbid Social Anxiety |
| NCT00177580 | Phase 4 | COMPLETED | Improving Symptoms of Schizophrenia and Schizoaffective Disorder by Supplementing Medications With Pravastatin |
| NCT00182442 | Phase 4 | COMPLETED | Cognition, Functioning and Quality of Life |
| NCT00182494 | Phase 4 | UNKNOWN | Diabetes Prevention Program in Schizophrenia [DPPS] |
| NCT00183625 | Phase 4 | COMPLETED | Supported Employment and Skills Training in Conjunction With Pharmacotherapy in Schizophrenia Patients |
| NCT00186771 | Phase 4 | UNKNOWN | Magnetic Stimulation as a Treatment for Auditory Hallucinations in Schizophrenia |
| NCT00190749 | Phase 4 | COMPLETED | Safety Study of Olanzapine and a Comparator in Patients With Schizophrenia and Schizoaffective Disorder |
| NCT00191555 | Phase 4 | COMPLETED | Efficacy Study of Switching Stabilized Schizophrenic Patients From Conventional to Atypical Antipsychotic Treatment |
| NCT00194025 | Phase 4 | COMPLETED | Valproate in Late Life Schizophrenia |
| NCT00199940 | Phase 4 | COMPLETED | Safety And Efficacy Study Of Ziprasidone In Pediatric Psychotic Illness |
| NCT00202306 | Phase 4 | COMPLETED | Indicated Prevention of Psychotic Disorders With Low-dose Lithium |
| NCT00203788 | Phase 4 | COMPLETED | Improving Work Outcome in People With Recent-onset Schizophrenia |
| NCT00204061 | Phase 4 | COMPLETED | Early Pharmacological and Psychological Intervention for Late Prodromal States of Psychosis |
| NCT00205660 | Phase 4 | COMPLETED | Changes in Adiposity, Metabolic Measures From Atypicals to Aripiprazole |
| NCT00206102 | Phase 4 | COMPLETED | A Study of the Cataractogenic Potential of Seroquel and Risperdal in the Treatment of Participants With Schizophrenia or Schizoaffective Disorder |
| NCT00208143 | Phase 4 | COMPLETED | Seroquel Therapy for Substance Use Disorders Comorbid With Schizophrenia |
| NCT00208169 | Phase 4 | COMPLETED | Abilify Therapy for Reducing Comorbid Substance Abuse |
| NCT00214578 | Phase 4 | COMPLETED | Seroquel on Glucose Metabolism |
| NCT00215579 | Phase 4 | COMPLETED | Determining the Effects of Risperdal Consta in Patients With Psychotic Disorders and Incomplete Adherence |
| NCT00216528 | Phase 4 | COMPLETED | A Study to Evaluate Symptomatic Remission in Schizophrenia With Long Acting Risperidone Microspheres |
| NCT00216632 | Phase 4 | COMPLETED | A Study of Treatment Success in Changing From Olanzapine to Long-acting Injectable Risperidone (RISPERDAL® CONSTA™) |
Predicted chemistry — Sugi Predict
The predicted patent-compound landscape for NOS2 across ~30M SureChEMBL compounds — explore on Sugi Predict.
Related Atlas pages
- Associated diseases: schizophrenia
- Targeted by drugs: Tilarginine
- Disease cohort memberships (association, not causation — diseases whose associated-gene cohort lists this gene; a subset are also under Associated diseases): malaria, susceptibility to
- Pharmacogenomically associated drugs (drugs whose metabolism/response is associated with variants in this gene (PharmGKB) — not drugs that target it): Isoniazid