NOS2

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
• Druggable target: yes — 10 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000625

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: 8 — 4 protein_coding, 3 nonsense_mediated_decay, 1 retained_intron

ENST00000313735, ENST00000646938, ENST00000697337, ENST00000697338, ENST00000697339, ENST00000697340, ENST00000697341, ENST00000886820

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.

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

281 total, 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

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.03

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
CAT	Repression

Upstream regulators (CollecTRI, top): AP1, APC, ATF2, BCL3, BCL6, CEBPA, CEBPB, CEBPD, CEBPG, CREB3L1, CTNNB1, CUX1, CXXC1, DNMT3B, ELF1, ELF2, ELF3, ELF4, ELK3, ESR1, ESR2, ETS1, ETS2, FOS, FOSL2, FOXC1, FOXO3, FUBP1, GLI3, HAND1, HHEX, HIF1A, HMGA1, HNF4A, HNRNPK, HR, IKBKB, IKZF1, IL33, IL6

miRNA regulators (miRDB)

55 targeting NOS2, 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-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

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		ENSRNOG00000078225

Paralogs (5): NOS1 (ENSG00000089250), MTRR (ENSG00000124275), POR (ENSG00000127948), NOS3 (ENSG00000164867), NDOR1 (ENSG00000188566)

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), 1 shown:

• 2 L-arginine + 3 NADPH + 4 O2 + H(+) = 2 L-citrulline + 2 nitric oxide + 3 NADP(+) + 4 H2O (RHEA:19897)

UniProt features (138 total): binding site 45, helix 31, 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.

PDB	Method	Resolution (Å)
6JWM	X-RAY DIFFRACTION	1.23
6KEY	X-RAY DIFFRACTION	1.24
5XN3	X-RAY DIFFRACTION	1.34
6JWN	X-RAY DIFFRACTION	1.61
3E7G	X-RAY DIFFRACTION	2.2
4NOS	X-RAY DIFFRACTION	2.25
3HR4	X-RAY DIFFRACTION	2.5
1NSI	X-RAY DIFFRACTION	2.55
3EJ8	X-RAY DIFFRACTION	2.55
2NSI	X-RAY DIFFRACTION	3
4CX7	X-RAY DIFFRACTION	3.16
2LL6	SOLUTION NMR
5TP6	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P35228-F1	85.66	0.66

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): 372; 373; 377; 381; 462; 463; 476; 491; 545; 546; 547; 549 …

Post-translational modifications (4): 234, 575, 578, 892

Mutagenesis-validated functional residues (1):

Position	Phenotype
27	loss of interaction with spsb1 and spsb4.

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-1222556	ROS and RNS production in phagocytes
R-HSA-392154	Nitric oxide stimulates guanylate cyclase
R-HSA-6785807	Interleukin-4 and Interleukin-13 signaling
R-HSA-9033241	Peroxisomal protein import
R-HSA-9636249	Inhibition of nitric oxide production

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 (30): response to hypoxia (GO:0001666), 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), obsolete nitric oxide mediated signal transduction (GO:0007263), 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), regulation of cell population proliferation (GO:0042127), 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), cellular response to lipopolysaccharide (GO:0071222), cellular response to type II interferon (GO:0071346), cellular response to xenobiotic stimulus (GO:0071466), 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

Rollup of top-5 pathways:

Category	Pathways
Innate Immune System	1
Platelet homeostasis	1
Signaling by Interleukins	1
Protein localization	1
Suppression of phagosomal maturation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
positive regulation of cytokine production	2
anion binding	2
binding	2
cation binding	2
cytoplasm	2
response to stress	1
response to decreased oxygen levels	1
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
L-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
defense response	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
peptidyl-cysteine modification	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

Protein interactions and networks

STRING

2976 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NOS2	CALML6	Q8TD86	941
NOS2	CALML3	P27482	941
NOS2	CALML4	Q96GE6	941
NOS2	CALML5	Q9NZT1	941
NOS2	CALM1	P02593	928
NOS2	PTGS2	P35354	903
NOS2	IFNG	P01579	861
NOS2	TNF	P01375	858
NOS2	ARG1	P05089	810
NOS2	IL1B	P01584	796
NOS2	IL6	P05231	782
NOS2	AKT1	P31749	776
NOS2	TLR4	O00206	754
NOS2	IL10	P22301	718
NOS2	ARG2	P78540	707

IntAct

22 interactions, top by confidence:

A	B	Type	Score
S100A9	S100A8	psi-mi:“MI:0914”(association)	0.750
S100A8	GAPDH	psi-mi:“MI:0914”(association)	0.650
GAPDH	S100A8	psi-mi:“MI:0914”(association)	0.650
NOS2	GAPDH	psi-mi:“MI:0915”(physical association)	0.500
GAPDH	NOS2	psi-mi:“MI:0915”(physical association)	0.500
NOS2	GAPDH	psi-mi:“MI:0914”(association)	0.500
NOS2	S100A8	psi-mi:“MI:0914”(association)	0.460
	NOS2	psi-mi:“MI:0407”(direct interaction)	0.440
NOS2	ADRM1	psi-mi:“MI:0915”(physical association)	0.400
NOS2	UCHL5	psi-mi:“MI:0915”(physical association)	0.400
NOS2		psi-mi:“MI:0915”(physical association)	0.400
S100A9	GAPDH	psi-mi:“MI:0914”(association)	0.350
NOS1	C1orf226	psi-mi:“MI:0914”(association)	0.350
INSR	BLTP3B	psi-mi:“MI:0914”(association)	0.350

BioGRID (216): NOS2 (Biochemical Activity), NOS2 (Co-crystal Structure), NOS2 (Reconstituted Complex), NOS2 (Affinity Capture-Western), NT5M (Negative Genetic), POMC (Negative Genetic), NOS2 (Negative Genetic), PIM1 (Negative Genetic), NOS2 (Negative Genetic), NOS2 (Negative Genetic), NOS2 (Negative Genetic), PIK3CG (Negative Genetic), NOS2 (Negative Genetic), PFKFB1 (Positive Genetic), NOS2 (Positive Genetic)

ESM2 similar proteins: A0A1W2PPD8, A1A5Q5, A2A3K4, A4H5X5, A7E379, B2RXH2, C0SUT9, D3ZKV9, F5HB62, O19132, O36371, O54705, O60291, O75164, O94953, P03177, P33802, P35228, Q1HVD1, Q29RJ0, Q3KSQ2, Q3U2K5, Q3UPF5, Q53WJ1, Q5R4R7, Q5R978, Q5RD88, Q5VW22, Q5VWQ0, Q6B0I6, Q6EEF3, Q6EMB2, Q6PI47, Q6X4W1, Q80T69, Q80TL4, Q8BFX3, Q8BW72, Q8CHB8, Q8K3Y6

Diamond homologs: A0A2U1KZS6, A0A2U1LIM9, A0A7T9QPQ1, A0KTH4, A1AEV0, A2QS05, A5F3I4, A6TD49, A7MJ63, A7ZQK7, A8A3P5, A8ANX1, A8G9X6, A9LZ73, A9MF16, B1IU77, C5YJG8, O08336, O08394, O19114, O19132, O32214, O54705, O62699, P00388, P00389, P04175, P14779, P16435, P16603, P19618, P29474, P29475, P29476, P29477, P35228, P36587, P37039, P37040, P37116

SIGNOR signaling

9 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”

Disease & clinical

Clinical variants and AI predictions

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

7616 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:27782994:A:G	W194R	1.000
17:27782994:A:T	W194R	1.000
17:27778947:A:G	W372R	0.999
17:27778947:A:T	W372R	0.999
17:27782966:C:G	R203T	0.999
17:27782974:G:C	C200W	0.999
17:27782976:A:G	C200R	0.999
17:27782990:C:G	R195P	0.999
17:27774346:A:G	W463R	0.998
17:27774346:A:T	W463R	0.998
17:27778696:A:C	S425R	0.998
17:27778696:A:T	S425R	0.998
17:27778698:T:G	S425R	0.998
17:27778709:G:T	A421D	0.998
17:27778898:C:G	R388P	0.998
17:27778949:C:T	G371D	0.998
17:27781122:A:G	W260R	0.998
17:27781122:A:T	W260R	0.998
17:27782965:C:A	R203S	0.998
17:27782965:C:G	R203S	0.998
17:27782966:C:A	R203M	0.998
17:27782992:C:A	W194C	0.998
17:27782992:C:G	W194C	0.998
17:27774320:G:C	S471R	0.997
17:27774320:G:T	S471R	0.997
17:27774322:T:G	S471R	0.997
17:27778919:C:G	R381P	0.997
17:27778931:T:A	E377V	0.997
17:27778951:A:C	N370K	0.997
17:27778951:A:T	N370K	0.997

dbSNP variants (sampled 300 via entrez): RS1000084421 (17:27793441 A>G), RS1000160472 (17:27798593 C>A,T), RS1000181446 (17:27802049 A>G), RS1000399133 (17:27767643 C>T), RS1000428823 (17:27767943 G>A), RS1000458096 (17:27793130 G>C), RS1000553923 (17:27774511 G>A,T), RS1000817167 (17:27773471 G>A), RS1000875968 (17:27763085 T>G), RS1000997627 (17:27763371 G>A), RS1001030322 (17:27757809 G>A), RS1001036959 (17:27779318 A>C,T), RS1001088374 (17:27773364 G>C), RS1001411350 (17:27779859 C>A), RS1001443552 (17:27798339 T>C)

Disease associations

OMIM: gene MIM:163730 | disease phenotypes: MIM:611162

GenCC curated gene-disease

Disease	Classification	Inheritance
schizophrenia	No Known Disease Relationship	Unknown

Mondo (2): malaria, susceptibility to (MONDO:0021024), schizophrenia (MONDO:0005090)

Orphanet (1): Malaria (Orphanet:673)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

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)

Molecules with ChEMBL bioactivity

10 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,037,755 (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
CHEMBL1371	CHLORZOXAZONE	4	16,752
CHEMBL140	CURCUMIN	3	93,882
CHEMBL1485	ARGININE	3	895,147
CHEMBL256147	TILARGININE	3	2,020
CHEMBL1093059	BARDOXOLONE	2	889
CHEMBL114551	GW-274150	2	1,052
CHEMBL1911882	KD7040	2	8
CHEMBL225304	PIMAGEDINE	2	24,450
CHEMBL7890	L-NAME	2	1,152
CHEMBL227744	NITROARGININE	1	2,403

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs11080344	Toxicity	3	isoniazid;rifampin	Toxic liver disease;Tuberculosis

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs11080344	NOS2	3	0.75	1	isoniazid;rifampin

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)

106 measured of 120 human assays (150 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
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
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
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
4,4,6a,6b,11,11,14b-heptamethyl-3,13-dioxo-8a-(4-pyridin-4-ylimidazole-1-carbonyl)-4a,5,6,6a,7,8,9,10,12,12a-decahydropicene-2-carbonitrile	IC50	9 nM	US-10189791: Pyridyl analogs of 1-(2-cyano-3,12-dioxooleana-1,9(11)dien-28-oyl) imidazole
6-[[(2R,4S)-4-[(6-amino-4-methyl-2-pyridinyl)methoxy]pyrrolidin-2-yl]methoxymethyl]-4-methylpyridin-2-amine	KI	10 nM	US-9732037: 2-aminopyridine-based selective neuronal nitric oxide synthase inhibitors
N’-[4-[3-(dimethylamino)propyl]-2,3-dihydro-1,4-benzothiazin-7-yl]thiophene-2-carboximidamide	IC50	14 nM	US-8618286: Benzoxazines, benzothiazines, and related compounds having NOS inhibitory activity
4,4,6a,6b,11,11,14b-heptamethyl-3,13-dioxo-8a-(4-phenylimidazole-1-carbonyl)-4a,5,6,6a,7,8,9,10,12,12a-decahydropicene-2-carbonitrile	IC50	14.7 nM	US-10189791: Pyridyl analogs of 1-(2-cyano-3,12-dioxooleana-1,9(11)dien-28-oyl) imidazole
N1-((3R,4S)-4-((6-aminopyridin-2-yl)methyl)pyrrolidin-3-yl)-N2-(4-fluorobenzyl)ethane-1,2-diamine tetrahydrochloride	KI	17.7 nM	US-9090589: Specific nNOS inhibitors for the therapy and prevention of human melanoma
7-[[5-(methylaminomethyl)-3-pyridinyl]oxymethyl]quinolin-2-amine	KI	19 nM	US-9783500: 2-aminoquinoline-based compounds for potent and selective neuronal nitric oxide synthase inhibition
7-[[3-[(dimethylamino)methyl]phenoxy]methyl]quinolin-2-amine	KI	21 nM	US-9783500: 2-aminoquinoline-based compounds for potent and selective neuronal nitric oxide synthase inhibition
7-(pyridin-3-yloxymethyl)quinolin-2-amine	KI	21 nM	US-9783500: 2-aminoquinoline-based compounds for potent and selective neuronal nitric oxide synthase inhibition
4-Methyl-6-propyl-pyridin-2-ylamine	IC50	23 nM
6-[2-[5-[(2R)-1-amino-3-(6-amino-4-methyl-2-pyridinyl)propan-2-yl]-3-pyridinyl]ethyl]-4-methylpyridin-2-amine	KI	24 nM	US-9951014: Mammalian and bacterial nitric oxide synthase inhibitors
N1-{(+/-)-4’-[(6’’-amino-4’’-methylpyridin-2’’-yl)methyl]pyrrolidin-3’-yl}-N2-phenethylethane-1,2-diamine tetrahydrochloride	KI	24 nM	US-9090589: Specific nNOS inhibitors for the therapy and prevention of human melanoma
6-[[(2S,4R)-4-[(6-amino-4-methyl-2-pyridinyl)methoxy]pyrrolidin-2-yl]methoxymethyl]-4-methylpyridin-2-amine	KI	26 nM	US-9732037: 2-aminopyridine-based selective neuronal nitric oxide synthase inhibitors
N’-[4-[3-(methylamino)propyl]-2,3-dihydro-1,4-benzothiazin-7-yl]thiophene-2-carboximidamide	IC50	28 nM	US-8618286: Benzoxazines, benzothiazines, and related compounds having NOS inhibitory activity
6-[2-[5-[1-amino-3-(6-amino-4-methyl-2-pyridinyl)propan-2-yl]-3-pyridinyl]ethyl]-4-methylpyridin-2-amine	KI	30 nM	US-9951014: Mammalian and bacterial nitric oxide synthase inhibitors
7-[[3-(dimethylamino)phenoxy]methyl]quinolin-2-amine	KI	31 nM	US-9783500: 2-aminoquinoline-based compounds for potent and selective neuronal nitric oxide synthase inhibition
6-[[(2S,4S)-4-[(6-amino-4-methyl-2-pyridinyl)methoxy]pyrrolidin-2-yl]methoxymethyl]-4-methylpyridin-2-amine	KI	31 nM	US-9732037: 2-aminopyridine-based selective neuronal nitric oxide synthase inhibitors
6-[[(2R)-3-amino-2-[(6-amino-4-methyl-2-pyridinyl)methoxy]propoxy]methyl]-4-methylpyridin-2-amine	KI	32 nM	US-9732037: 2-aminopyridine-based selective neuronal nitric oxide synthase inhibitors
N’-[4-[2-(2-hydroxyethylamino)ethyl]-2,3-dihydro-1,4-benzothiazin-7-yl]thiophene-2-carboximidamide	IC50	34 nM	US-8618286: Benzoxazines, benzothiazines, and related compounds having NOS inhibitory activity
6-[[(2R,4R)-4-[(6-amino-4-methyl-2-pyridinyl)methoxy]pyrrolidin-2-yl]methoxymethyl]-4-methylpyridin-2-amine	KI	34 nM	US-9732037: 2-aminopyridine-based selective neuronal nitric oxide synthase inhibitors
7-[[3-[2-(methylamino)ethyl]phenoxy]methyl]quinolin-2-amine	KI	36 nM	US-9783500: 2-aminoquinoline-based compounds for potent and selective neuronal nitric oxide synthase inhibition
6-[[(2S,3S)-2-amino-3-[(6-amino-4-methyl-2-pyridinyl)methoxy]butoxy]methyl]-4-methylpyridin-2-amine	KI	37 nM	US-9732037: 2-aminopyridine-based selective neuronal nitric oxide synthase inhibitors
NOS Inhibitor, 3h	KI	38 nM
6-[[3-[[2-(3-fluorophenyl)ethylamino]methyl]phenoxy]methyl]-4-methylpyridin-2-amine	KI	40 nM	US-9732037: 2-aminopyridine-based selective neuronal nitric oxide synthase inhibitors
7-[[5-[(1S)-1-(methylamino)ethyl]-3-pyridinyl]oxymethyl]quinolin-2-amine	KI	46 nM	US-9783500: 2-aminoquinoline-based compounds for potent and selective neuronal nitric oxide synthase inhibition
6-[[(2R,3R)-2-amino-3-[(6-amino-4-methyl-2-pyridinyl)methoxy]butoxy]methyl]-4-methylpyridin-2-amine	KI	47 nM	US-9732037: 2-aminopyridine-based selective neuronal nitric oxide synthase inhibitors
N’-[4-[2-(ethylamino)ethyl]-2,3-dihydro-1,4-benzothiazin-6-yl]thiophene-2-carboximidamide	IC50	50 nM	US-8618286: Benzoxazines, benzothiazines, and related compounds having NOS inhibitory activity
7-[[3-(methylaminomethyl)anilino]methyl]quinolin-2-amine	KI	51 nM	US-9783500: 2-aminoquinoline-based compounds for potent and selective neuronal nitric oxide synthase inhibition
7-[[3-[2-(dimethylamino)ethoxy]phenoxy]methyl]quinolin-2-amine	KI	52 nM	US-9783500: 2-aminoquinoline-based compounds for potent and selective neuronal nitric oxide synthase inhibition
6-[2-[3-[1-amino-3-(6-amino-4-methyl-2-pyridinyl)propan-2-yl]phenyl]ethyl]-4-methylpyridin-2-amine	KI	53 nM	US-9951014: Mammalian and bacterial nitric oxide synthase inhibitors
7-[[4-chloro-3-(methylaminomethyl)phenoxy]methyl]quinolin-2-amine	KI	54 nM	US-9783500: 2-aminoquinoline-based compounds for potent and selective neuronal nitric oxide synthase inhibition
3-[2-(6-amino-4-methyl-2-pyridinyl)ethyl]-5-[methyl-[2-(methylamino)ethyl]amino]benzonitrile	KI	55 nM	US-9951014: Mammalian and bacterial nitric oxide synthase inhibitors
7-[[4-fluoro-3-(methylaminomethyl)phenoxy]methyl]quinolin-2-amine	KI	56 nM	US-9783500: 2-aminoquinoline-based compounds for potent and selective neuronal nitric oxide synthase inhibition
N’-[3-[2-(6-amino-4-methyl-2-pyridinyl)ethyl]phenyl]-N’-methylethane-1,2-diamine	KI	56 nM	US-9951014: Mammalian and bacterial nitric oxide synthase inhibitors
N’-[4-[2-(methylamino)ethyl]-2,3-dihydro-1,4-benzothiazin-7-yl]thiophene-2-carboximidamide	IC50	60 nM	US-8618286: Benzoxazines, benzothiazines, and related compounds having NOS inhibitory activity
6-[[3-(3-aminopropoxy)phenoxy]methyl]-4-methylpyridin-2-amine	KI	60 nM	US-9732037: 2-aminopyridine-based selective neuronal nitric oxide synthase inhibitors
7-[[5-[(1R)-1-(methylamino)ethyl]-3-pyridinyl]oxymethyl]quinolin-2-amine	KI	65 nM	US-9783500: 2-aminoquinoline-based compounds for potent and selective neuronal nitric oxide synthase inhibition
2-(6-amino-4-methyl-2-pyridinyl)-1-[3-[2-(6-amino-4-methyl-2-pyridinyl)ethyl]phenyl]ethanol	KI	70 nM	US-9951014: Mammalian and bacterial nitric oxide synthase inhibitors
6-[2-[5-[(2S)-1-amino-3-(6-amino-4-methyl-2-pyridinyl)propan-2-yl]-3-pyridinyl]ethyl]-4-methylpyridin-2-amine	KI	70 nM	US-9951014: Mammalian and bacterial nitric oxide synthase inhibitors
6-[2-[[(2S,4R)-4-[(6-amino-4-methyl-2-pyridinyl)methoxy]pyrrolidin-2-yl]methoxy]ethoxymethyl]-4-methylpyridin-2-amine	KI	70 nM	US-9732037: 2-aminopyridine-based selective neuronal nitric oxide synthase inhibitors
7-[[5-[1-(methylamino)ethyl]-3-pyridinyl]oxymethyl]quinolin-2-amine	KI	74 nM	US-9783500: 2-aminoquinoline-based compounds for potent and selective neuronal nitric oxide synthase inhibition
7-[[3-[(dimethylamino)methyl]anilino]methyl]quinolin-2-amine	KI	78 nM	US-9783500: 2-aminoquinoline-based compounds for potent and selective neuronal nitric oxide synthase inhibition
N’-[4-[2-(methylamino)ethyl]-2,3-dihydro-1,4-benzoxazin-6-yl]thiophene-2-carboximidamide	IC50	80 nM	US-8618286: Benzoxazines, benzothiazines, and related compounds having NOS inhibitory activity
N’-[4-[2-(methylamino)ethyl]-2,3-dihydro-1,4-benzothiazin-6-yl]thiophene-2-carboximidamide	IC50	80 nM	US-8618286: Benzoxazines, benzothiazines, and related compounds having NOS inhibitory activity
6,6’-[(5-aminobenzene-1,3-diyl)diethane-2,1-diyl]bis(4-methylpyridin-2-amine)	KI	85 nM
N1-{(+/-)-4’-[(6’’-amino-4’’-methylpyridin-2’’-yl)methyl]pyrrolidin-3’-yl}ethane-1,2-diamine tetrahydrochloride	KI	98 nM	US-9090589: Specific nNOS inhibitors for the therapy and prevention of human melanoma
6,6’-(pyridine-2,6-diyldiethane-2,1-diyl)bis(4-methylpyridin-2-amine)	KI	99 nM	US-9951014: Mammalian and bacterial nitric oxide synthase inhibitors
N’-[3-[2-(6-amino-4-methyl-2-pyridinyl)ethyl]-5-fluorophenyl]-N,N’-dimethylethane-1,2-diamine	KI	105 nM	US-9951014: Mammalian and bacterial nitric oxide synthase inhibitors

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

859 with measured affinity, of 1582 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

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

Chemical	Actions (top 5)	PubMed papers
Lipopolysaccharides	decreases reaction, increases expression, increases chemical synthesis, increases abundance, increases activity (+5 more)	28
Nitric Oxide	increases expression, increases activity, increases reaction, affects cotreatment, decreases expression (+10 more)	24
Resveratrol	increases expression, decreases reaction, decreases stability, decreases expression, affects reaction (+4 more)	8
Benzo(a)pyrene	decreases reaction, increases expression, increases reaction, affects methylation, affects expression (+2 more)	7
Quercetin	decreases reaction, increases expression, affects cotreatment, decreases expression	7
Particulate Matter	affects response to substance, increases abundance, affects methylation, decreases methylation, increases expression	7
Plant Extracts	decreases reaction, increases expression, decreases chemical synthesis, increases reaction, decreases expression (+1 more)	6
pyrrolidine dithiocarbamic acid	decreases reaction, increases expression, affects cotreatment	5
Air Pollutants	affects methylation, decreases methylation, increases abundance, increases expression, affects response to substance (+2 more)	5
Glucose	affects reaction, decreases reaction, affects expression, increases expression	5
Tetradecanoylphorbol Acetate	affects cotreatment, increases reaction, decreases reaction, increases expression	5
Valproic Acid	affects cotreatment, decreases expression, increases expression	5
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	decreases expression, decreases reaction, increases expression, increases reaction, affects cotreatment	3
SB 203580	affects cotreatment, decreases reaction, increases expression	3
U 0126	decreases expression, decreases reaction, increases expression	3
Acetylcysteine	decreases reaction, increases expression, affects cotreatment, decreases expression	3
Cadmium	increases abundance, increases expression, decreases reaction	3
Curcumin	increases activity, decreases reaction, increases expression	3
Cycloheximide	decreases reaction, increases expression, affects cotreatment	3
Doxorubicin	decreases expression, increases expression, increases reaction	3
Chlorpyrifos	increases expression	3
Glucosamine	decreases expression, decreases reaction, increases expression, increases reaction, affects cotreatment	3
Melitten	decreases reaction, increases chemical synthesis, increases expression, decreases expression	3
Methotrexate	decreases reaction, increases chemical synthesis, increases expression	3
Mustard Gas	decreases expression, increases expression, decreases reaction	3
Nitroprusside	increases chemical synthesis, increases expression, affects cotreatment, decreases activity, decreases reaction	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)

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

Trial	Phase	Status	Title
NCT00000374	PHASE4	COMPLETED	Treatment for First-Episode Schizophrenia
NCT00001656	PHASE4	COMPLETED	Comparison of Clozapine vs Olanzapine in Childhood-Onset Psychotic Disorders
NCT00007774	PHASE4	COMPLETED	To Determine if Olanzapine is More Cost Effective Than Haloperidol for the Treatment of Schizophrenia
NCT00014001	PHASE4	COMPLETED	CATIE- Schizophrenia Trial
NCT00018668	PHASE4	COMPLETED	Antipsychotic Response in Schizophrenia
NCT00034801	PHASE4	COMPLETED	Olanzapine Versus Active Comparator in the Treatment of Depression in Patients With Schizophrenia
NCT00034905	PHASE4	COMPLETED	A Comparison of Seroquel vs. Risperidone in Schizophrenia
NCT00036088	PHASE4	COMPLETED	Olanzapine Versus An Active Comparator in the Treatment of Schizophrenia
NCT00044187	PHASE4	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	PHASE4	COMPLETED	Switching Medication to Treat Schizophrenia
NCT00048828	PHASE4	COMPLETED	Treating Drug-Resistant Childhood Schizophrenia
NCT00053703	PHASE4	COMPLETED	Treatment of Early Onset Schizophrenia Spectrum Disorders (TEOSS)
NCT00056498	PHASE4	COMPLETED	Risperidone Treatment in Schizophrenia Patients Who Are Currently Taking Clozapine
NCT00061802	PHASE4	COMPLETED	Efficacy and Safety of Two Atypical Antipsychotics vs. Placebo in Patients With an Acute Exacerbation of Either Schizophrenia or Schizoaffective Disorder
NCT00080327	PHASE4	COMPLETED	Study of Three Doses of Aripiprazole in Patients With Acute Schizophrenia
NCT00088049	PHASE4	COMPLETED	Study of Olanzapine vs. Aripiprazole in the Treatment of Schizophrenia
NCT00090012	PHASE4	COMPLETED	Comparison of Continuing Olanzapine to Switching to Quetiapine in Overweight or Obese Patients With Schizophrenia and Schizoaffective Disorder
NCT00100776	PHASE4	COMPLETED	Efficacy of High Dose Olanzapine for the Treatment of Schizophrenia and Schizoaffective Disorder
NCT00103571	PHASE4	COMPLETED	Olanzapine Versus Aripiprazole in the Treatment of Acutely Ill Patients With Schizophrenia
NCT00108368	PHASE4	COMPLETED	The Effects of Risperidone and Olanzapine on Thinking
NCT00114595	PHASE4	COMPLETED	Ethyl-Eicosapentaenoic Acid and Tardive Dyskinesia
NCT00130923	PHASE4	COMPLETED	Risperidone Long-acting Versus Oral Risperidone in Patients With Schizophrenia and Alcohol Use Disorder
NCT00137020	PHASE4	COMPLETED	Clinical Effect Of Cross Titration Of Antipsychotics With Ziprasidone In Schizophrenia Or Schizoaffective Disorder
NCT00140166	PHASE4	COMPLETED	Treatment of Acute Schizophrenia With Vitamin Therapy
NCT00145847	PHASE4	COMPLETED	Naltrexone Treatment of Alcohol Abuse in Schizophrenia
NCT00148564	PHASE4	COMPLETED	Energy Homeostasis Under Treatment With Atypical Antipsychotics
NCT00156715	PHASE4	COMPLETED	Efficacy of Quetiapine in the Treatment of Patients With Schizophrenia and a Comorbid Substance Use Disorder
NCT00158223	PHASE4	COMPLETED	Effectiveness of Pimozide in Augmenting the Effects of Clozapine in the Treatment of Schizophrenia
NCT00159081	PHASE4	COMPLETED	One Year Drug Treatment in First-Episode Schizophrenia
NCT00159120	PHASE4	COMPLETED	Maintenance Treatment vs. Stepwise Drug Discontinuation in First-Episode Schizophrenia
NCT00159133	PHASE4	COMPLETED	Prodrome-Based Early Intervention With Antipsychotics vs. Benzodiazepines in First-Episode Schizophrenia
NCT00159757	PHASE4	TERMINATED	12 Week Open, Non-Comparative Switch Study Of Oral Ziprazidone In Previously Treated Schizophrenic Patients
NCT00167817	PHASE4	COMPLETED	Effect of Switch to Aripiprazole on Health and Smoking Parameters in Patients With Schizophrenia: A Pilot Study
NCT00169026	PHASE4	TERMINATED	Alcoholism and Schizophrenia: Effects of Clozapine
NCT00169039	PHASE4	TERMINATED	Clozapine Versus Chlorpromazine for Treatment-Unresponsive Schizophrenia
NCT00169065	PHASE4	COMPLETED	Effectiveness of Clozapine Versus Olanzapine for Treatment-resistant Schizophrenia
NCT00169091	PHASE4	TERMINATED	Clozapine Versus Haloperidol for Treating the First Episode of Schizophrenia
NCT00176423	PHASE4	COMPLETED	Efficacy Study of Galantamine for Cognitive Impairments in Schizophrenia
NCT00176436	PHASE4	COMPLETED	Atomoxetine for Treatment of Weight Gain in Olanzapine or Clozapine Patients
NCT00177008	PHASE4	COMPLETED	Aripiprazole for the Treatment of Schizophrenia With Co-Morbid Social Anxiety