TPH2

Summary

TPH2 (tryptophan hydroxylase 2, HGNC:20692) is a protein-coding gene on chromosome 12q21.1, encoding Tryptophan 5-hydroxylase 2 (Q8IWU9).

This gene encodes a member of the pterin-dependent aromatic acid hydroxylase family. The encoded protein catalyzes the first and rate limiting step in the biosynthesis of serotonin, an important hormone and neurotransmitter. Mutations in this gene may be associated with psychiatric diseases such as bipolar affective disorder and major depression.

Source: NCBI Gene 121278 — RefSeq curated summary.

At a glance

• Gene–disease (curated): attention deficit-hyperactivity disorder, susceptibility to, 7 (Limited, GenCC)
• Clinical variants (ClinVar): 78 total
• GTEx eGene: eQTL in 2 tissues, sQTL in 0 (q < 0.05)
• Drug target: yes — 3 via a complex or family; 3 molecules with ChEMBL bioactivity
• Approved drugs acting on a complex or family including it: 3 — Telotristat, Telotristat Ethyl, Telotristat Etiprate (Tryptophan 5-hydroxylase)
• Constraint (gnomAD): pLI 0.72 (intermediate), LOEUF 0.55 (moderately constrained)
• MANE Select transcript: NM_173353
• Notable: 78 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20692
Approved symbol	TPH2
Name	tryptophan hydroxylase 2
Location	12q21.1
Locus type	gene with protein product
Status	Approved
Aliases	NTPH, FLJ37295
Ensembl gene	ENSG00000139287
Ensembl biotype	protein_coding
OMIM	607478
Entrez	121278

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 5 protein_coding_CDS_not_defined, 1 protein_coding

MANE Select: ENST00000333850

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 3: 4, TSL 5: 1

ENST00000333850, ENST00000546576, ENST00000547278, ENST00000547348, ENST00000550403, ENST00000551074

RefSeq mRNA: 1 — MANE Select: NM_173353 NM_173353

CCDS: CCDS31859

Canonical transcript exons

ENST00000333850 — 11 exons

Exon	Start	End
ENSE00001291881	72031521	72032440
ENSE00001293573	71972519	71972715
ENSE00001302379	72022399	72022494
ENSE00001312687	72031258	72031391
ENSE00001313536	71978952	71979087
ENSE00001339312	71938845	71939091
ENSE00001716058	71994439	71994565
ENSE00003495110	71944586	71944686
ENSE00003496311	71949588	71949655
ENSE00003503906	71944294	71944477
ENSE00003561457	71941584	71941733

Expression profiles

Bgee: expression breadth ubiquitous, 111 present calls, max score 86.40.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.3706 / max 122.9257, expressed in 39 samples.

Highest expression (Bgee): secondary oocyte, male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, oocyte, superior vestibular nucleus.

Genetic regulation across tissues (GTEx eQTL / sQTL)

TPH2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 2 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

2 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Brain Cortex	eqtl	1.4e-02	+0.29	12:72776660:C:T
Brain Frontal Cortex BA9	eqtl	3.1e-02	-0.35	12:72447223:T:C

FANTOM5 promoters

6 alternative TSS:

Promoter ID	TPM avg	Samples expressed
126839	0.2383	18
126842	0.0589	6
126840	0.0487	21
126841	0.0152	4
126844	0.0061	2
126845	0.0034	2

Top tissues by expression

showing 100 of 204 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	86.40	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.39	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	77.38	gold quality
oocyte	CL:0000023	73.00	gold quality
superior vestibular nucleus	UBERON:0007227	70.33	gold quality
islet of Langerhans	UBERON:0000006	61.57	gold quality
sural nerve	UBERON:0015488	60.61	silver quality
prefrontal cortex	UBERON:0000451	56.10	gold quality
adenohypophysis	UBERON:0002196	52.80	gold quality
pituitary gland	UBERON:0000007	52.16	gold quality
medulla oblongata	UBERON:0001896	51.83	silver quality
testis	UBERON:0000473	50.68	gold quality
leukocyte	CL:0000738	50.14	gold quality
monocyte	CL:0000576	50.08	gold quality
left testis	UBERON:0004533	49.05	gold quality
frontal cortex	UBERON:0001870	48.61	gold quality
ganglionic eminence	UBERON:0004023	48.45	gold quality
right uterine tube	UBERON:0001302	48.35	gold quality
right testis	UBERON:0004534	48.09	gold quality
stromal cell of endometrium	CL:0002255	47.87	gold quality
pancreas	UBERON:0001264	47.72	gold quality
hindlimb stylopod muscle	UBERON:0004252	47.71	gold quality
gastrocnemius	UBERON:0001388	47.67	gold quality
neocortex	UBERON:0001950	47.33	gold quality
Brodmann (1909) area 9	UBERON:0013540	46.76	gold quality
muscle of leg	UBERON:0001383	46.64	gold quality
spleen	UBERON:0002106	46.61	gold quality
upper leg skin	UBERON:0004262	46.58	silver quality
skin of leg	UBERON:0001511	46.40	gold quality
mucosa of stomach	UBERON:0001199	46.30	gold quality
gall bladder	UBERON:0002110	46.26	gold quality
skin of abdomen	UBERON:0001416	46.05	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	45.86	gold quality
cerebral cortex	UBERON:0000956	45.67	gold quality
rectum	UBERON:0001052	45.64	gold quality
zone of skin	UBERON:0000014	45.46	gold quality
endometrium	UBERON:0001295	45.45	silver quality
ventricular zone	UBERON:0003053	45.32	gold quality
hypothalamus	UBERON:0001898	45.02	gold quality
anterior cingulate cortex	UBERON:0009835	44.78	gold quality
duodenum	UBERON:0002114	44.63	gold quality
skin of hip	UBERON:0001554	44.56	silver quality
smooth muscle tissue	UBERON:0001135	44.12	gold quality
mucosa of transverse colon	UBERON:0004991	43.81	silver quality
forebrain	UBERON:0001890	43.40	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
muscle layer of sigmoid colon	UBERON:0035805	43.35	gold quality
Ammon’s horn	UBERON:0001954	43.20	gold quality
liver	UBERON:0002107	43.17	silver quality
uterus	UBERON:0000995	43.10	silver quality
brain	UBERON:0000955	42.87	gold quality
muscle tissue	UBERON:0002385	42.82	silver quality
olfactory segment of nasal mucosa	UBERON:0005386	42.82	silver quality
small intestine	UBERON:0002108	42.49	gold quality
superior frontal gyrus	UBERON:0002661	42.33	gold quality
intestine	UBERON:0000160	42.30	gold quality
lower esophagus mucosa	UBERON:0035834	42.21	silver quality
vermiform appendix	UBERON:0001154	42.16	silver quality
popliteal artery	UBERON:0002250	42.14	silver quality
colon	UBERON:0001155	42.12	gold quality
tibial artery	UBERON:0007610	42.11	silver quality
large intestine	UBERON:0000059	42.09	gold quality
colonic epithelium	UBERON:0000397	42.08	gold quality
fundus of stomach	UBERON:0001160	42.06	silver quality
female reproductive system	UBERON:0000474	42.03	silver quality
right lung	UBERON:0002167	41.99	silver quality
anatomical system	UBERON:0000467	41.98	gold quality
body of uterus	UBERON:0009853	41.95	silver quality
material anatomical entity	UBERON:0000465	41.94	gold quality
multicellular organism	UBERON:0000468	41.93	gold quality
nasal cavity mucosa	UBERON:0001826	41.68	silver quality
vagina	UBERON:0000996	41.65	silver quality
left ovary	UBERON:0002119	41.62	silver quality
caecum	UBERON:0001153	41.53	silver quality
vastus lateralis	UBERON:0001379	41.41	gold quality
quadriceps femoris	UBERON:0001377	41.37	gold quality
substantia nigra	UBERON:0002038	41.35	gold quality
superficial temporal artery	UBERON:0001614	41.33	gold quality
right frontal lobe	UBERON:0002810	41.33	gold quality
blood	UBERON:0000178	41.21	gold quality
body of stomach	UBERON:0001161	41.16	gold quality
ovary	UBERON:0000992	41.13	silver quality
midbrain	UBERON:0001891	41.12	gold quality
small intestine Peyer’s patch	UBERON:0003454	41.12	silver quality
palpebral conjunctiva	UBERON:0001812	41.10	gold quality
oviduct epithelium	UBERON:0004804	41.07	gold quality
endocervix	UBERON:0000458	41.06	silver quality
C1 segment of cervical spinal cord	UBERON:0006469	41.06	silver quality
fallopian tube	UBERON:0003889	41.03	silver quality
lymph node	UBERON:0000029	41.02	gold quality
stomach	UBERON:0000945	40.99	gold quality
aorta	UBERON:0000947	40.98	silver quality
mucosa of paranasal sinus	UBERON:0005030	40.98	gold quality
spinal cord	UBERON:0002240	40.93	silver quality
cortex of kidney	UBERON:0001225	40.90	gold quality
amniotic fluid	UBERON:0000173	40.69	gold quality
jejunal mucosa	UBERON:0000399	40.59	gold quality
biceps brachii	UBERON:0001507	40.57	gold quality
placenta	UBERON:0001987	40.50	silver quality
epithelium of nasopharynx	UBERON:0001951	40.45	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.83
E-MTAB-7249	no	53.42
E-GEOD-100618	no	29.96

HPA expression

RNA tissue specificity: Not detected

showing 60 of 103 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Liver	tissue	739.5	low
Periaqueductal gray	tissue	63.3
Pons	tissue	62.2
Locus coeruleus	tissue	19.6
Appendix	tissue	15.6	low
Medulla oblongata	tissue	12.9
Basal ganglia	tissue	9.5	not detected
Cerebellum	tissue	7.8	not detected
Urinary bladder	tissue	7.1	low
Olfactory bulb	tissue	6.5
Cerebral cortex	tissue	6.4	not detected
Amygdala	tissue	6.4
Insular cortex	tissue	6.4
Corpus callosum	tissue	6.2
Retrosplenial cortex	tissue	6.0
Putamen	tissue	5.9
Retrosplenial and cingulate cortex	tissue	5.9
Temporal cortex	tissue	5.9
Occipital cortex	tissue	5.6
Basal ganglia	tissue	5.5	not detected
Hippocampal formation	tissue	5.4
Entorhinal cortex	tissue	5.4
Ventral forebrain	tissue	5.3
Prefrontal cortex	tissue	5.1
Motor cortex	tissue	5.0
Septum	tissue	5.0
Periaqueductal gray	tissue	4.7
Somatosensory cortex	tissue	4.7
Putamen	tissue	4.5
Hypothalamus	tissue	4.4
Substantia nigra	tissue	4.2
Spinal cord	tissue	4.1
Pituitary gland	tissue	3.8
Midbrain	tissue	3.6
Medulla oblongata	tissue	3.6
Duodenum	tissue	3.4	low
Superior colliculi	tissue	3.3
Pons	tissue	3.0
Thalamus	tissue	3.0
Lymph node	tissue	2.9	not detected
Ventral forebrain	tissue	2.7
Small intestine	tissue	2.6	low
Smooth muscle	tissue	2.5	low
Tonsil	tissue	2.5	low
Postcentral gyrus	tissue	2.3
Septum	tissue	2.2
Lung	tissue	1.7	not detected
Gallbladder	tissue	1.7	not detected
Stomach 1	tissue	1.6	low
Frontal cortex	tissue	1.5
Caudate putamen	tissue	1.4
Rectum	tissue	1.3	low
Hippocampus	tissue	1.2	not detected
Spleen	tissue	1.2	not detected
Colon	tissue	1.1	low
Substantia nigra	tissue	0.9
Postcentral gyrus	tissue	0.8
Hippocampal formation	tissue	0.6
Epididymis	tissue	0.6	not detected
Olfactory bulb	tissue	0.5

Brain sub-regions (HPA Brain Atlas): detected in 324; highest nTPM — Median raphe nucleus (631.8), Dorsal raphe nucleus (397.0), Pontine raphe nucleus (271.3), Nucleus raphe pallidus (96.1), Paramedian reticular nucleus (84.7).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting TPH2 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-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-219A-5P	99.91	73.36	735
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-4782-3P	99.88	73.31	735
HSA-MIR-6766-3P	99.88	73.38	732
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-8080	99.82	67.52	1342
HSA-MIR-8076	99.78	68.52	1170
HSA-MIR-3685	99.62	68.83	1621
HSA-MIR-1290	99.59	69.90	2079
HSA-MIR-425-5P	99.59	67.67	900
HSA-MIR-141-5P	99.57	67.86	897
HSA-MIR-4762-5P	99.57	68.54	1424
HSA-MIR-1252-3P	99.55	67.71	2862
HSA-MIR-372-5P	99.41	69.11	2299
HSA-MIR-4721	99.26	66.05	818
HSA-MIR-642A-3P	99.23	67.67	1258

Functional genomics

gnomAD constraint: pLI 0.722, LOEUF 0.547, missense Z 1.44 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000333850 — one region, missense o/e 0.89.

Literature-anchored findings (GeneRIF, showing 40)

• a second tryptophan hydroxylase isoform described (PMID:12511643)
• Single-nucleotide polymorphism (SNP), haplotype and linkage disequlibrium studies were performed on depressed patients and healthy controls with 10 SNPs in the TPH2 gene. Significant association was detected between one SNP and major depression. (PMID:15124006)
• complex behavioral phenotypes or as actual risk factors. Structural polymorphisms are extremely rare in TPH2 and cannot therefore act as substantial risk factors for behavioral disorders in African-American and Caucasian populations. (PMID:15167691)
• It is unlikely that the hCV245410-hCV8376173-rs-1487280 haplotypes of TPH2 were involved in the suicidal behavior of 336 Canadian bipolar patients. (PMID:15197398)
• Single nucleotide polymorphism data support existence of an affective disorder-associated haplotype in the THP2 gene. (PMID:15263906)
• The findings of this study provide evidence for an involvement of genetic variants in the TPH2 gene in suicidal behavior. (PMID:15476687)
• Identification of a loss-of-function mutation in hTPH2 suggests that defect in brain serotonin synthesis may represent an important risk factor for unipolar major depression. (PMID:15629698)
• TPH2 may play a modest role in autism susceptibility. (PMID:15768392)
• Eight single nucleotide polymorphisms in the TPH2 gene for association with attention-deficit hyperactivity disorder in 179 Irish nuclear families. (PMID:15940290)
• TPH2 mRNA levels in postmortem parietal cortex of unipolar-depressed, bipolar, and schizophrenic patients vs control subjects, using real-time reverse transcription polymerase chain reaction. No significant difference in TPH2 mRNA levels was found. (PMID:15968084)
• In vivo evidence that a relatively frequent regulatory variant (G(-844)T) of hTPH2 biases the reactivity of the amygdala, a neural structure critical in the generation and regulation of emotional behaviors. (PMID:16044172)
• Preferential transmissions were detected for the two SNPs in TPH2’s regulatory region (rs4570625, rs11178997). (PMID:16116490)
• Here, we used functional magnetic resonance imaging (fMRI) to demonstrate that a potentially functional variant of TPH2 modulates amygdala responsiveness to emotional stimuli of both negative and positive valence. (PMID:16245070)
• this first study of TPH2 in panic disorder argue against an importance of allelic variation of TPH2 in the pathogenesis of panic disorder (PMID:16401665)
• No association with history of suicide was found for the -473T > A and -8396G > C polymorphisms of the TPH2 gene in subjects with schizophrenia or bipolar disorder. (PMID:16436194)
• our results do not confirm the role of the R441H mutation of the hTPH2 gene in the susceptibility to unipolar major depression (PMID:16581035)
• the NH(2)-terminal regulatory domain is the source of hTPH2 instability and reduced solubility. (PMID:16864580)
• Variant is not a major determinant of genetic risk for depression in aged patients. (PMID:16936760)
• It appears unlikely that the TPH1 and TPH2 genes play a significant role in the susceptibility to autism or to autism endophenotypes including severe obsessive-compulsive behaviors and self-stimulatory behaviors. (PMID:16958027)
• The A allele was significantly less frequent in patients with suicide behavior. Individuals with the A/A genotype showed a significantly lower risk of suicide behavior than those with the A/G or G/G genotype. (PMID:17011525)
• Haplotype-based analysis of TPH2 in patients with UP and BP disorder provides preliminary evidence for protective association in both disorders and thus supports a central role for TPH2 in the pathogenesis of affective disorders. (PMID:17015812)
• A larger sample size will be required to clarify if TPH2 alleles are or are not associated with ADHD. (PMID:17123708)
• an association with rs1386494 SNP was observed in the subgroup of female patients with pure PD phenotype, indicating a possible gender-specific effect of TPH2 gene variants in panic disorder. (PMID:17123728)
• Case-control studies support the presence of a susceptibility locus for bipolar disorder in tryptophan hydroxylase 2. (PMID:17167340)
• A significant association between harm avoidance (HA), a trait related to anxiety, and tryptophan hydroxylase 2 polymorphism (PMID:17176491)
• these findings implicate alterations of serotonin synthesis in emotion regulation and confirm TPH2 as a susceptibility and/or modifier gene of affective spectrum disorders (PMID:17176492)
• Absence of the Arg441His polymorphism in the tryptophan hydroxylase 2 gene in adults with anxiety disorders and depression. (PMID:17192895)
• study reports the learning process of decision-making in suicide attempters to be modulated by four serotonergic gene polymorphisms, 5HTTLPR, TPH1 A218C, MAOA u-VNTR, and TPH2 rs1118997 (PMID:17221847)
• Haplotypes of the TPH2 gene are unlikely to play a major role in the pathophysiology of alcohol dependence or the alcoholism-related phenotype suicidal behavior. (PMID:17251907)
• single-nucleotide polymorphism on the TPH2 gene explained more than 10% of the variance in both indicators of attention (PMID:17335389)
• TPH2 gene variants are unlikely to contribute to autism or to the presence/absence of prominent repetitive behaviors in our sample, although an influence on the intensity of these behaviors in autism cannot be excluded (PMID:17346350)
• Polymorphism in this enzyme is not associated with schizophrenia in a Japanese population. (PMID:17413454)
• Results reveal the presence of a functional cis-acting polymorphism, with high frequency in normal human subjects, resulting in increased TPH2 expression levels. (PMID:17453063)
• These data identify a region between the C-terminal oligomerization domain and the catalytic domain, which is indispensable for TPH2 activity. (PMID:17539919)
• human TPH2 promoter polymorphism impacts on gene expression, which might have implications for the development and function of the serotonergic system in the brain (PMID:17568567)
• Results link TPH2 variations to pathogenesis of Tourette syndrome and support the relevance of serotonin signalling in Tourette’s. (PMID:17592484)
• No association was detected between the rs4131347 (-C8347G) SNP in the promoter region of the TPH2 gene and mood disorders, suicidal behavior or monoamine function. (PMID:17604842)
• hopelessness, negative life-events and family history of suicide were risk factors of attempted suicide in major deprbssion while TPH2 gene rs7305115 A/A might be the protective factor. (PMID:17649681)
• This study supports the involvement of TPH2 in the etiology of BPD, and the functional single-nucleotide polymorphisms identified herein might be the susceptibility loci for BPD (PMID:17768266)
• The results of this study underscore the role of the TPH2 G-703T polymorphism in the modulation of behavior and cognition. (PMID:17892388)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	tph2	ENSDARG00000057239
mus_musculus	Tph2	ENSMUSG00000006764
rattus_norvegicus	Tph2	ENSRNOG00000003880
drosophila_melanogaster	Trhn	FBGN0035187

Paralogs (3): TPH1 (ENSG00000129167), PAH (ENSG00000171759), TH (ENSG00000180176)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:2651811) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 57 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased serotonin level	6
decreased body weight	3
postnatal growth retardation	2
decreased coping response	2
postnatal lethality, incomplete penetrance	2
abnormal liver morphology	1
small liver	1
abnormal spleen morphology	1
enlarged spleen	1
weakness	1
abnormal hippocampus morphology	1
abnormal ovary morphology	1
abnormal testis morphology	1
enlarged testis	1
abnormal skin condition	1
decreased body length	1
decreased body size	1
persistence of hyaloid vascular system	1
increased aggression towards male mice	1
increased aggression towards female mice	1
increased anxiety-related response	1
abnormal mating preference	1
abnormal pup retrieval	1
pup cannibalization	1
abnormal maternal nurturing	1

+32 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
Macaca mulatta	Q2HZ26	98.8%	Diamond
Oryctolagus cuniculus	P17290	95.5%	Diamond
Equus caballus	Q0EAB8	95.1%	Diamond
Bos taurus	Q2KIH7	92.5%	Diamond
Oncorhynchus mykiss	A0A060X6Z0	89.8%	Diamond
Anguilla anguilla	O42091	89.8%	Diamond
Canis lupus familiaris	Q76IQ3	88.3%	Diamond
Caenorhabditis briggsae	A8X3V8	88.1%	Diamond
Gallus gallus	P70080	88.1%	Diamond
Caenorhabditis elegans	P90986	88.1%	Diamond
Xenopus laevis	Q92142	88.1%	Diamond
Phasianidae sp.	P11982	78.9%	Diamond
Chromobacterium violaceum ATCC 12472	P30967	73.9%	Diamond
Ralstonia pseudosolanacearum GMI1000	Q8XU39	73.9%	Diamond
Pinus taeda	E5KBU3	69.8%	Diamond
Physcomitrium patens	E5KBU4	69.8%	Diamond
Caulobacter vibrioides CB15	Q9A7V7	63.4%	Diamond
Pseudomonas aeruginosa PAO1	P43334	59.3%	Diamond
Vibrio cholerae O1 biovar El Tor str. N16961	Q9KLB8	59.3%	Diamond
Chlamydomonas reinhardtii	A8HQD7	59.0%	Diamond
Schistosoma mansoni	O17446	56.1%	Diamond
Dictyostelium discoideum	Q54XS1	55.5%	Diamond
Aquifex aeolicus VF5	O67085	50.0%	Diamond
Mesorhizobium japonicum MAFF 303099	Q98D72	49.8%	Diamond
Methanocaldococcus jannaschii DSM 2661	Q58054	47.8%	Diamond
Streptomyces coeruleorubidus	F5BFC8	39.0%	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
RAB21	protein-coding	23011
TRHDE-AS1	ncRNA	283392
TRHDE	protein-coding	29953
TBC1D15	protein-coding	64786
LINC03242	ncRNA	105369838
FAABTP	protein-coding	55266
LINC02444	ncRNA	101928137

Protein

Protein identifiers

Tryptophan 5-hydroxylase 2 — Q8IWU9 (reviewed: Q8IWU9)

Alternative names: Neuronal tryptophan hydroxylase, Tryptophan 5-monooxygenase 2

All UniProt accessions (1): Q8IWU9

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. Interacts with DNAJC12.

Tissue specificity. Brain specific.

Disease relevance. Major depressive disorder (MDD) [MIM:608516] A common psychiatric disorder. It is a complex trait characterized by one or more major depressive episodes without a history of manic, mixed, or hypomanic episodes. A major depressive episode is characterized by at least 2 weeks during which there is a new onset or clear worsening of either depressed mood or loss of interest or pleasure in nearly all activities. Four additional symptoms must also be present including changes in appetite, weight, sleep, and psychomotor activity; decreased energy; feelings of worthlessness or guilt; difficulty thinking, concentrating, or making decisions; or recurrent thoughts of death or suicidal ideation, plans, or attempts. The episode must be accompanied by distress or impairment in social, occupational, or other important areas of functioning. Disease susceptibility is associated with variants affecting the gene represented in this entry. Attention deficit-hyperactivity disorder 7 (ADHD7) [MIM:613003] A neurobehavioral developmental disorder primarily characterized by the coexistence of attentional problems and hyperactivity, with each behavior occurring infrequently alone. Disease susceptibility is associated with variants affecting the gene represented in this entry. Naturally occurring variants of TPH2 with impaired enzyme activity could cause deficiency of serotonin production and result in an increased risk of developing behavioral disorders.

Pathway. Aromatic compound metabolism; serotonin biosynthesis; serotonin from L-tryptophan: step 1/2.

Similarity. Belongs to the biopterin-dependent aromatic amino acid hydroxylase family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8IWU9-1	a	yes
Q8IWU9-2	b

RefSeq proteins (1): NP_775489* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001273	ArAA_hydroxylase	Family
IPR002912	ACT_dom	Domain
IPR005963	Trp_5_mOase	Family
IPR018301	ArAA_hydroxylase_Fe/CU_BS	Binding_site
IPR019773	Tyrosine_3-monooxygenase-like	Family
IPR019774	Aromatic-AA_hydroxylase_C	Domain
IPR036329	Aro-AA_hydroxylase_C_sf	Homologous_superfamily
IPR036951	ArAA_hydroxylase_sf	Homologous_superfamily
IPR041904	TrpOH_cat	Domain
IPR045865	ACT-like_dom_sf	Homologous_superfamily

Pfam: PF00351

Enzyme classification (BRENDA)

• EC 1.14.16.4 — tryptophan 5-monooxygenase (BRENDA: 37 organisms, 147 substrates, 229 inhibitors, 123 Km, 18 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
L-TRYPTOPHAN	0.002–1.67	46
TETRAHYDROBIOPTERIN	0.0067–0.324	18
(6R)-L-ERYTHO-5,6,7,8-TETRAHYDROBIOPTERIN	0.0128–0.281	9
L-PHENYLALANINE	0.022–0.102	7
(6R)-L-ERYTHRO-5,6,7,8-TETRAHYDROBIOPTERIN	0.0179–0.796	4
2-AMINO-4-HYDROXY-6-METHYLTETRAHYDROPTERIDINE	0.055–0.125	4
2-AMINO-4-HYDROXY-6,7-DIMETHYL-5,6,7,8-TETRAHYDR	0.006–0.13	3
O2	0.039–0.273	3
TRYPTOPHAN	0.05–0.29	3
6-METHYL-TETRAHYDROPTERIN	0.053–0.802	2
6-METHYLTETRAHYDROPTERIN	0.0146–0.177	2
(6R)-5,6,7,8-TETRAHYDROBIOPTERIN	0.045	1
(7R)-5,6,7,8-TETRAHYDROBIOPTERIN	2.1	1
2-AMINO-4-HYDROXY-6-METHYL-5,6,7,8-TETRAHYDROPTE	0.05	1
2-AZAISOTRYPTOPHAN	0.0865	1

Catalyzed reactions (Rhea)

• (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin + L-tryptophan + O2 = 5-hydroxy-L-tryptophan + (4aS,6R)-4a-hydroxy-L-erythro-5,6,7,8-tetrahydrobiopterin (RHEA:16709)

UniProt features (67 total): helix 24, strand 16, sequence variant 12, turn 4, binding site 3, compositionally biased region 2, chain 1, domain 1, region of interest 1, sequence conflict 1, modified residue 1, splice variant 1

Structure

Experimental structures (PDB)

5 structures by resolution:

PDB	Title	Method	Resolution (Å)
4V06	Crystal structure of human tryptophan hydroxylase 2 (TPH2), catalytic domain	X-RAY DIFFRACTION	2.63
9HB8	Crystal structure of human tryptophan hydroxylase 2 in complex with inhibitor KM-06-098	X-RAY DIFFRACTION	2.9
9HB7	Crystal structure of human tryptophan hydroxylase 2 in complex with inhibitor AG-01-128	X-RAY DIFFRACTION	2.96
7WIY	Cryo-EM structure of human TPH2 tetramer	ELECTRON MICROSCOPY	3.09
7QRI	Regulatory domain dimer of tryptophan hydroxylase 2 in complex with L-Phe	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IWU9-F1	83.55	0.55

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Oxidoreductases, Metabolic proteins, Predicted intracellular proteins, Disease related genes, FDA approved drug targets, Small molecule drugs, Human disease related genes, Mental and behavioural disorders

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 (3)

Position	Role
318	Fe cation
323	Fe cation
363	Fe cation

Post-translational modifications (1)

Type	Positions
Phosphoserine	19

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 4; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

4 pathways:

ID	Pathway	Evidence
R-HSA-209931	Serotonin and melatonin biosynthesis	curated
R-HSA-1430728	Metabolism	—
R-HSA-209776	Metabolism of amine-derived hormones	—
R-HSA-71291	Metabolism of amino acids and derivatives	—

MSigDB gene sets: 104 (showing top): GOBP_PHENOL_CONTAINING_COMPOUND_METABOLIC_PROCESS, GOBP_PHENOL_CONTAINING_COMPOUND_BIOSYNTHETIC_PROCESS, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_PAIRED_DONORS_WITH_INCORPORATION_OR_REDUCTION_OF_MOLECULAR_OXYGEN, TAL1ALPHAE47_01, GOBP_AROMATIC_AMINO_ACID_METABOLIC_PROCESS, BRN2_01, chr12q21, GATA6_01, GOBP_INDOLE_CONTAINING_COMPOUND_METABOLIC_PROCESS, GOBP_ORGANIC_ACID_METABOLIC_PROCESS, GOCC_NEURON_PROJECTION, YKACATTT_UNKNOWN, GOMF_IRON_ION_BINDING, CHEN_METABOLIC_SYNDROM_NETWORK, TAL1BETAITF2_01

GO Biological Process (2): aromatic amino acid metabolic process (GO:0009072), serotonin biosynthetic process (GO:0042427)

GO Molecular Function (6): tryptophan 5-monooxygenase activity (GO:0004510), iron ion binding (GO:0005506), monooxygenase activity (GO:0004497), oxidoreductase activity (GO:0016491), oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced pteridine as one donor, and incorporation of one atom of oxygen (GO:0016714), metal ion binding (GO:0046872)

GO Cellular Component (2): cytosol (GO:0005829), neuron projection (GO:0043005)

Reactome top-level categories

3 top-level categories:

Category	Pathways
Metabolism of amine-derived hormones	1
Metabolism of amino acids and derivatives	1
Metabolism	1

GO top-level categories

16 GO namespaces:

Category	Terms
amino acid metabolic process	1
carboxylic acid metabolic process	1
serotonin metabolic process	1
indole-containing compound biosynthetic process	1
phenol-containing compound biosynthetic process	1
primary amino compound biosynthetic process	1
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced pteridine as one donor, and incorporation of one atom of oxygen	1
transition metal ion binding	1
oxidoreductase activity	1
catalytic activity	1
monooxygenase activity	1
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen	1
cation binding	1
cytoplasm	1
cellular anatomical structure	1
plasma membrane bounded cell projection	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 1 of 10 annotations. The rest are phylogenetic / computational / electronic (IEA).

1 experimentally-supported GO terms:

GO term	NS	Evidence
tryptophan 5-monooxygenase activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 1,182 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TPH2	SLC6A4	P31645	871
TPH2	HTR1B	P28222	800
TPH2	YWHAZ	P29213	772
TPH2	HTR2A	P28223	754
TPH2	HTR2C	P28335	735
TPH2	MAOA	P21397	735
TPH2	MAOB	P27338	708
TPH2	HTR1D	P28221	680
TPH2	DDC	P20711	676
TPH2	HTR1A	P08908	675
TPH2	AANAT	Q16613	666
TPH2	YWHAH	Q04917	656
TPH2	DRD4	P21917	643
TPH2	YWHAB	P31946	633
TPH2	FEV	Q99581	598

IntAct

Human interaction partners of TPH2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

3 partners by confidence:

Partner	Interaction type	MIscore	Records
DNAJC12	physical association	0.400	1
TPH1	physical association	0.400	1
YWHAE	association	0.350	1

BioGRID (8 interactions; top human partners by supporting records): DNAJC12 (Affinity Capture-MS; 2 records), SYBU (Affinity Capture-MS; 2 records), EEF2 (Cross-Linking-MS (XL-MS)), NUDT21 (Affinity Capture-RNA), TPH1 (Affinity Capture-MS)

SIGNOR signaling

3 signaling interactions:

A	Effect	B	Mechanism
PRKACA	up-regulates	TPH2	phosphorylation
TPH2	“down-regulates quantity”	tryptophan	“chemical modification”
TPH2	“up-regulates quantity”	5-hydroxy-L-tryptophan	“chemical modification”

Disease & clinical

Genetic variants

Variant evidence for TPH2: 78 ClinVar records (0 pathogenic / likely pathogenic).

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	63
Likely benign	2
Benign	5

AlphaMissense

1,594 missense substitutions predicted likely pathogenic (of 3,217 scored), across 357 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
H318	8	0.999	1.000
H323	8	0.999	1.000
D315	8	0.998	1.000
H179	8	0.997	1.000
F287	8	0.996	1.000
F296	8	0.996	1.000
D184	8	0.990	0.998
D286	8	0.990	0.997
H304	8	0.987	0.998
F359	8	0.987	1.000
D162	8	0.984	0.998
F182	8	0.980	1.000
F400	8	0.976	0.999
F360	8	0.973	1.000
F273	8	0.971	1.000
F364	8	0.970	1.000
D176	8	0.967	0.990
F84	8	0.966	0.997
F335	8	0.966	0.999
F332	8	0.950	0.998

HPA cancer prognostics

RNA cancer specificity: Not detected

Disease associations

OMIM: gene MIM:607478 | disease phenotypes:

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
attention deficit-hyperactivity disorder, susceptibility to, 7	Limited	Autosomal dominant

Mondo (1): attention deficit-hyperactivity disorder, susceptibility to, 7 (MONDO:0013076)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3831287 (PROTEIN FAMILY), CHEMBL5433 (SINGLE PROTEIN)

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 TPH2 — the drug acts on the assembly or class, not necessarily on this subunit alone.

3 drugs via a complex or family:

Drug	Target (ChEMBL)	Members	Max phase
TELOTRISTAT	Tryptophan 5-hydroxylase	2	4
TELOTRISTAT ETHYL	Tryptophan 5-hydroxylase	2	4
TELOTRISTAT ETIPRATE	Tryptophan 5-hydroxylase	2	4

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 591 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

3 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL2103855	TELOTRISTAT	4	335
CHEMBL2105695	TELOTRISTAT ETHYL	4	202
CHEMBL4104957	RODATRISTAT	2	54

PharmGKB: 1 entry (CPIC guideline: no)

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Amino acid hydroxylases

Most potent curated ligand interactions (2 total), top 2:

Ligand	Action	Affinity	Parameter
rodatristat	Inhibition	8.15	pIC50
TPT-004	Inhibition	7.8	pIC50

Binding affinities (BindingDB)

128 measured of 146 human assays (146 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
Xermelo	IC50	16 nM
CHEMBL5438308	IC50	18 nM
CHEMBL5399835	IC50	22 nM
CHEMBL5436189	IC50	23 nM
(2S)-2-amino-3-(4-(2-amino-6-(2,2,2-trifluoro-1-(2-(furan-2-yl)phenyl)ethoxy)pyrimidin-4-yl)phenyl)propanoic acid	IC50	24 nM
CHEMBL5438753	IC50	24 nM
CHEMBL5415902	IC50	24 nM
CHEMBL5413327	IC50	25 nM
CHEMBL5435257	IC50	26 nM
(S) -2-amino-3-[4-(2-amino-6-[2,2,2-trifluoro-1-(2-(3-trifluoromethyl-pyrazol-1-yl-phenyl)-ethoxy]-pyrimidin-4-yl]-phenyl-propionic acid	IC50	29 nM
CHEMBL5430916	IC50	31 nM
CHEMBL5394907	IC50	32 nM
CHEMBL5397488	IC50	32 nM
CHEMBL4104957	IC50	33 nM
Ex. 15/KM-06-96/(I-15)	IC50	34 nM	US-10683309: Xanthine derivatives, their use as a medicament, and pharmaceutical preparations comprising the same
CHEMBL5438647	IC50	34 nM
CHEMBL5416130	IC50	37 nM
CHEMBL5413920	IC50	37 nM
CHEMBL5398093	IC50	38 nM
KM-05-179/(I-201)	IC50	40 nM	US-10214530
CHEMBL5438865	IC50	41 nM
CHEMBL5408404	IC50	51 nM
CHEMBL5411613	IC50	52 nM
Ex. 16/KM-06-97/(I-16)	IC50	54 nM	US-10683309: Xanthine derivatives, their use as a medicament, and pharmaceutical preparations comprising the same
(2S)-2-amino-3-(4-(2-amino-6-(2,2,2-trifluoro-1-(3-(furan-2-yl)thiophen-2-yl)ethoxy)pyrimidin-4-yl) phenyl)propanoic acid	IC50	54 nM
Ex. 30/KM-06-150/(I-30)	IC50	56 nM	US-10683309: Xanthine derivatives, their use as a medicament, and pharmaceutical preparations comprising the same
CHEMBL5421206	IC50	57 nM
CHEMBL5415966	IC50	57 nM
CHEMBL5420292	IC50	58 nM
CHEMBL5414714	IC50	58 nM
CHEMBL5421152	IC50	63 nM
Ex. 32/KM-06-153/(I-32)	IC50	69 nM	US-10683309: Xanthine derivatives, their use as a medicament, and pharmaceutical preparations comprising the same
CHEMBL5412796	IC50	69 nM
(S)-2-Amino-3-(4-{2-amino-6-[2,2,2-trifluoro-1-(3’-methylbiphenyl-2-yl)-ethoxy]-pyrimidin-4-yl}-phenyl)propionic acid	IC50	70 nM
Ex. 17/KM-06-98/(I-17)	IC50	84 nM	US-10683309: Xanthine derivatives, their use as a medicament, and pharmaceutical preparations comprising the same
Ex. 28/KM-06-148/(I-28)	IC50	116 nM	US-10683309: Xanthine derivatives, their use as a medicament, and pharmaceutical preparations comprising the same
CHEMBL5435958	IC50	116 nM
Ex. 27/KM-06-115/(I-27)	IC50	133 nM	US-10683309: Xanthine derivatives, their use as a medicament, and pharmaceutical preparations comprising the same
CHEMBL5435077	IC50	152 nM
Ex. 21/KM-06-108/(I-21)	IC50	162 nM	US-10683309: Xanthine derivatives, their use as a medicament, and pharmaceutical preparations comprising the same
CHEMBL5435288	IC50	176 nM
Ex. 7/KM-06-81/(I-7)	IC50	177 nM	US-10683309: Xanthine derivatives, their use as a medicament, and pharmaceutical preparations comprising the same
Ex. 39/KM-06-180/(I-39)	IC50	179 nM	US-10683309: Xanthine derivatives, their use as a medicament, and pharmaceutical preparations comprising the same
Ex. 4/KM-06-78/(I-4)	IC50	198 nM	US-10683309: Xanthine derivatives, their use as a medicament, and pharmaceutical preparations comprising the same
Ex. 18/KM-06-99/(I-18)	IC50	209 nM	US-10683309: Xanthine derivatives, their use as a medicament, and pharmaceutical preparations comprising the same
Ex. 13/KM-06-66/(I-13)	IC50	213 nM	US-10683309: Xanthine derivatives, their use as a medicament, and pharmaceutical preparations comprising the same
Ex. 26/KM-06-114/(I-26)	IC50	217 nM	US-10683309: Xanthine derivatives, their use as a medicament, and pharmaceutical preparations comprising the same
Ex. 8/KM-06-82/(I-8)	IC50	219 nM	US-10683309: Xanthine derivatives, their use as a medicament, and pharmaceutical preparations comprising the same
Ex. 38/KM-06-176/(I-38)	IC50	220 nM	US-10683309: Xanthine derivatives, their use as a medicament, and pharmaceutical preparations comprising the same
Ex. 20/KM-06-107/(I-20)	IC50	225 nM	US-10683309: Xanthine derivatives, their use as a medicament, and pharmaceutical preparations comprising the same

ChEMBL bioactivities

240 potent at pChembl≥5 of 244 total, top 45 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.15	IC50	7	nM	RODATRISTAT
7.96	IC50	11	nM	CHEMBL5395489
7.85	IC50	14	nM	CHEMBL5191481
7.85	IC50	14	nM	CHEMBL5173430
7.85	IC50	14	nM	CHEMBL5416480
7.82	IC50	15	nM	CHEMBL5424626
7.80	IC50	16	nM	CHEMBL5397485
7.80	IC50	16	nM	CHEMBL5407430
7.80	IC50	16	nM	CHEMBL5404510
7.77	IC50	17	nM	CHEMBL5420432
7.77	IC50	17	nM	CHEMBL5423163
7.77	IC50	17	nM	CHEMBL5435460
7.77	IC50	17	nM	CHEMBL5394253
7.75	IC50	18	nM	CHEMBL5408595
7.75	IC50	18	nM	CHEMBL5438521
7.75	IC50	18	nM	CHEMBL5438308
7.72	IC50	19	nM	CHEMBL5169479
7.70	IC50	20	nM	CHEMBL5203888
7.70	IC50	20	nM	CHEMBL5197055
7.70	IC50	20	nM	CHEMBL5172829
7.70	IC50	20	nM	CHEMBL5413997
7.70	IC50	20	nM	CHEMBL5420586
7.70	IC50	20	nM	CHEMBL5421387
7.70	IC50	20	nM	CHEMBL5169479
7.68	IC50	21	nM	CHEMBL5423736
7.66	IC50	22	nM	CHEMBL5399835
7.64	IC50	23	nM	CHEMBL5407978
7.64	IC50	23	nM	CHEMBL5436189
7.62	IC50	24	nM	CHEMBL5440400
7.62	IC50	24	nM	CHEMBL5438753
7.62	IC50	24	nM	CHEMBL5415902
7.60	IC50	25	nM	CHEMBL5413327
7.60	IC50	25	nM	CHEMBL5416684
7.58	IC50	26	nM	CHEMBL5404599
7.58	IC50	26	nM	CHEMBL5435257
7.54	IC50	29	nM	CHEMBL5396844
7.52	IC50	30	nM	CHEMBL5426838
7.52	IC50	30	nM	CHEMBL5437935
7.52	IC50	30	nM	CHEMBL5424419
7.51	IC50	31	nM	CHEMBL5423548
7.51	IC50	31	nM	CHEMBL5430916
7.50	IC50	32	nM	CHEMBL5440685
7.50	IC50	32	nM	CHEMBL5394907
7.50	IC50	32	nM	CHEMBL5397488
7.47	IC50	34	nM	CHEMBL5438647

PubChem BioAssay actives

107 with measured affinity, of 116 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
(3S)-8-[2-amino-6-[(1R)-1-(4-chloro-2-phenylphenyl)-2,2,2-trifluoroethoxy]pyrimidin-4-yl]-2,8-diazaspiro[4.5]decane-3-carboxylic acid	1434619: Inhibition of TPH2 (unknown origin)	ic50	0.0070	uM
7-benzyl-3-ethyl-8-(imidazo[2,1-b][1,3]thiazol-6-ylmethyl)purine-2,6-dione	2021089: Inhibition of recombinant MBP-tagged full length human THP2 using L-Trp as substrate assessed as formation of 5-HTP by measuring fluorescent property	ic50	0.0110	uM
7-benzyl-8-(5H-[1,3]dioxolo[4,5-f]benzimidazol-6-ylmethyl)-3-propylpurine-2,6-dione	1885932: Inhibition of N-terminal MBP-tagged full length human TPH2 assessed as reduction in 5-HTP formation incubated for 5 to 10 mins by fluorescence microplate reader analysis	ic50	0.0140	uM
3-ethyl-8-(imidazo[2,1-b][1,3]thiazol-6-ylmethyl)-7-[[4-(1-methylpyrazol-3-yl)phenyl]methyl]purine-2,6-dione	2021089: Inhibition of recombinant MBP-tagged full length human THP2 using L-Trp as substrate assessed as formation of 5-HTP by measuring fluorescent property	ic50	0.0140	uM
7-benzyl-8-(5H-[1,3]dioxolo[4,5-f]benzimidazol-6-ylmethyl)-3-ethylpurine-2,6-dione	1885932: Inhibition of N-terminal MBP-tagged full length human TPH2 assessed as reduction in 5-HTP formation incubated for 5 to 10 mins by fluorescence microplate reader analysis	ic50	0.0140	uM
7-benzyl-8-[(2-chloroimidazo[2,1-b][1,3]thiazol-6-yl)methyl]-3-ethylpurine-2,6-dione	2021089: Inhibition of recombinant MBP-tagged full length human THP2 using L-Trp as substrate assessed as formation of 5-HTP by measuring fluorescent property	ic50	0.0150	uM
7-benzyl-3-ethyl-8-[(2-methylimidazo[2,1-b][1,3]thiazol-6-yl)methyl]purine-2,6-dione	2021089: Inhibition of recombinant MBP-tagged full length human THP2 using L-Trp as substrate assessed as formation of 5-HTP by measuring fluorescent property	ic50	0.0160	uM
N-[4-[[3-ethyl-8-[(2-methylimidazo[2,1-b][1,3]thiazol-6-yl)methyl]-2,6-dioxopurin-7-yl]methyl]phenyl]acetamide	2021089: Inhibition of recombinant MBP-tagged full length human THP2 using L-Trp as substrate assessed as formation of 5-HTP by measuring fluorescent property	ic50	0.0160	uM
3-ethyl-8-[(2-methylimidazo[2,1-b][1,3]thiazol-6-yl)methyl]-7-(oxetan-3-ylmethyl)purine-2,6-dione	2021089: Inhibition of recombinant MBP-tagged full length human THP2 using L-Trp as substrate assessed as formation of 5-HTP by measuring fluorescent property	ic50	0.0160	uM
3-ethyl-8-(imidazo[1,2-a]pyridin-2-ylmethyl)-7-[[4-(1-methylpyrazol-3-yl)phenyl]methyl]purine-2,6-dione	2021089: Inhibition of recombinant MBP-tagged full length human THP2 using L-Trp as substrate assessed as formation of 5-HTP by measuring fluorescent property	ic50	0.0170	uM
3-ethyl-8-(imidazo[1,2-a]pyridin-2-ylmethyl)-7-[[4-(1,3-thiazol-2-yl)phenyl]methyl]purine-2,6-dione	2021089: Inhibition of recombinant MBP-tagged full length human THP2 using L-Trp as substrate assessed as formation of 5-HTP by measuring fluorescent property	ic50	0.0170	uM
3-ethyl-8-[(2-methylimidazo[2,1-b][1,3]thiazol-6-yl)methyl]-7-[[4-(2-oxopyrrolidin-1-yl)phenyl]methyl]purine-2,6-dione	2021089: Inhibition of recombinant MBP-tagged full length human THP2 using L-Trp as substrate assessed as formation of 5-HTP by measuring fluorescent property	ic50	0.0170	uM
N-[4-[[8-[(2-chloroimidazo[2,1-b][1,3]thiazol-6-yl)methyl]-3-ethyl-2,6-dioxopurin-7-yl]methyl]phenyl]acetamide	2021089: Inhibition of recombinant MBP-tagged full length human THP2 using L-Trp as substrate assessed as formation of 5-HTP by measuring fluorescent property	ic50	0.0170	uM
7-benzyl-3-ethyl-8-[(2-methylimidazo[2,1-b][1,3,4]thiadiazol-6-yl)methyl]purine-2,6-dione	2021089: Inhibition of recombinant MBP-tagged full length human THP2 using L-Trp as substrate assessed as formation of 5-HTP by measuring fluorescent property	ic50	0.0180	uM
3-ethyl-8-(imidazo[1,2-a]pyridin-2-ylmethyl)-7-[[4-(5-methyl-1,2,4-oxadiazol-3-yl)phenyl]methyl]purine-2,6-dione	2021089: Inhibition of recombinant MBP-tagged full length human THP2 using L-Trp as substrate assessed as formation of 5-HTP by measuring fluorescent property	ic50	0.0180	uM
3-ethyl-8-[(2-methylimidazo[2,1-b][1,3]thiazol-6-yl)methyl]-7-(pyridin-2-ylmethyl)purine-2,6-dione	2021089: Inhibition of recombinant MBP-tagged full length human THP2 using L-Trp as substrate assessed as formation of 5-HTP by measuring fluorescent property	ic50	0.0180	uM
8-(1H-benzimidazol-2-ylmethyl)-7-benzyl-3-ethylpurine-2,6-dione	1885932: Inhibition of N-terminal MBP-tagged full length human TPH2 assessed as reduction in 5-HTP formation incubated for 5 to 10 mins by fluorescence microplate reader analysis	ic50	0.0190	uM
8-(1H-benzimidazol-2-ylmethyl)-7-benzyl-3-propylpurine-2,6-dione	1885932: Inhibition of N-terminal MBP-tagged full length human TPH2 assessed as reduction in 5-HTP formation incubated for 5 to 10 mins by fluorescence microplate reader analysis	ic50	0.0200	uM
3-ethyl-8-(imidazo[1,2-a]pyridin-2-ylmethyl)-7-[[4-(3-methyl-1,2,4-oxadiazol-5-yl)phenyl]methyl]purine-2,6-dione	2021089: Inhibition of recombinant MBP-tagged full length human THP2 using L-Trp as substrate assessed as formation of 5-HTP by measuring fluorescent property	ic50	0.0200	uM
3-ethyl-8-(imidazo[1,2-a]pyridin-2-ylmethyl)-7-[(4-pyrimidin-2-ylphenyl)methyl]purine-2,6-dione	2021089: Inhibition of recombinant MBP-tagged full length human THP2 using L-Trp as substrate assessed as formation of 5-HTP by measuring fluorescent property	ic50	0.0200	uM
methyl 4-[[3-ethyl-8-(imidazo[1,2-a]pyridin-2-ylmethyl)-2,6-dioxopurin-7-yl]methyl]benzoate	2021089: Inhibition of recombinant MBP-tagged full length human THP2 using L-Trp as substrate assessed as formation of 5-HTP by measuring fluorescent property	ic50	0.0200	uM
7-benzyl-8-[(6-hydroxy-1H-benzimidazol-2-yl)methyl]-3-propylpurine-2,6-dione	1885932: Inhibition of N-terminal MBP-tagged full length human TPH2 assessed as reduction in 5-HTP formation incubated for 5 to 10 mins by fluorescence microplate reader analysis	ic50	0.0200	uM
7-benzyl-8-[(6-ethoxy-1H-benzimidazol-2-yl)methyl]-3-ethylpurine-2,6-dione	1885932: Inhibition of N-terminal MBP-tagged full length human TPH2 assessed as reduction in 5-HTP formation incubated for 5 to 10 mins by fluorescence microplate reader analysis	ic50	0.0200	uM
3-ethyl-8-[(2-methylimidazo[2,1-b][1,3]thiazol-6-yl)methyl]-7-[[4-(1-methylpyrazol-3-yl)phenyl]methyl]purine-2,6-dione	2021089: Inhibition of recombinant MBP-tagged full length human THP2 using L-Trp as substrate assessed as formation of 5-HTP by measuring fluorescent property	ic50	0.0210	uM
methyl 3-[[3-ethyl-8-[(2-methylimidazo[2,1-b][1,3]thiazol-6-yl)methyl]-2,6-dioxopurin-7-yl]methyl]benzoate	2021089: Inhibition of recombinant MBP-tagged full length human THP2 using L-Trp as substrate assessed as formation of 5-HTP by measuring fluorescent property	ic50	0.0220	uM
8-[(2-chloroimidazo[2,1-b][1,3]thiazol-6-yl)methyl]-3-ethyl-7-[[4-(1,2,4-triazol-1-yl)phenyl]methyl]purine-2,6-dione	2021089: Inhibition of recombinant MBP-tagged full length human THP2 using L-Trp as substrate assessed as formation of 5-HTP by measuring fluorescent property	ic50	0.0230	uM
7-(cyclopropylmethyl)-3-ethyl-8-[(2-methylimidazo[2,1-b][1,3]thiazol-6-yl)methyl]purine-2,6-dione	2021089: Inhibition of recombinant MBP-tagged full length human THP2 using L-Trp as substrate assessed as formation of 5-HTP by measuring fluorescent property	ic50	0.0230	uM
8-[(2-chloroimidazo[2,1-b][1,3]thiazol-6-yl)methyl]-3-ethyl-7-[[4-(1-methylpyrazol-3-yl)phenyl]methyl]purine-2,6-dione	2021089: Inhibition of recombinant MBP-tagged full length human THP2 using L-Trp as substrate assessed as formation of 5-HTP by measuring fluorescent property	ic50	0.0240	uM
3-ethyl-8-[(2-methylimidazo[2,1-b][1,3]thiazol-6-yl)methyl]-7-propan-2-ylpurine-2,6-dione	2021089: Inhibition of recombinant MBP-tagged full length human THP2 using L-Trp as substrate assessed as formation of 5-HTP by measuring fluorescent property	ic50	0.0240	uM
3-ethyl-8-[(2-methylimidazo[2,1-b][1,3]thiazol-6-yl)methyl]-7-[(6-methyl-2-pyridinyl)methyl]purine-2,6-dione	2021089: Inhibition of recombinant MBP-tagged full length human THP2 using L-Trp as substrate assessed as formation of 5-HTP by measuring fluorescent property	ic50	0.0240	uM
3-ethyl-7-[(4-methoxyphenyl)methyl]-8-[(2-methylimidazo[2,1-b][1,3]thiazol-6-yl)methyl]purine-2,6-dione	2021089: Inhibition of recombinant MBP-tagged full length human THP2 using L-Trp as substrate assessed as formation of 5-HTP by measuring fluorescent property	ic50	0.0250	uM
methyl 3-[[3-ethyl-2,6-dioxo-8-(5,6,7,8-tetrahydroimidazo[1,2-a]pyridin-2-ylmethyl)purin-7-yl]methyl]benzoate	2021089: Inhibition of recombinant MBP-tagged full length human THP2 using L-Trp as substrate assessed as formation of 5-HTP by measuring fluorescent property	ic50	0.0250	uM
3-ethyl-7-[[4-(5-methyl-1,2,4-oxadiazol-3-yl)phenyl]methyl]-8-(5,6,7,8-tetrahydroimidazo[1,2-a]pyridin-2-ylmethyl)purine-2,6-dione	2021089: Inhibition of recombinant MBP-tagged full length human THP2 using L-Trp as substrate assessed as formation of 5-HTP by measuring fluorescent property	ic50	0.0260	uM
ethyl 4-[3-ethyl-8-[(2-methylimidazo[2,1-b][1,3]thiazol-6-yl)methyl]-2,6-dioxopurin-7-yl]butanoate	2021089: Inhibition of recombinant MBP-tagged full length human THP2 using L-Trp as substrate assessed as formation of 5-HTP by measuring fluorescent property	ic50	0.0260	uM
3-ethyl-7-[(4-imidazol-1-ylphenyl)methyl]-8-(5,6,7,8-tetrahydroimidazo[1,2-a]pyridin-2-ylmethyl)purine-2,6-dione	2021089: Inhibition of recombinant MBP-tagged full length human THP2 using L-Trp as substrate assessed as formation of 5-HTP by measuring fluorescent property	ic50	0.0290	uM
3-ethyl-7-[[4-(2-oxopyrrolidin-1-yl)phenyl]methyl]-8-(5,6,7,8-tetrahydroimidazo[1,2-a]pyridin-2-ylmethyl)purine-2,6-dione	2021089: Inhibition of recombinant MBP-tagged full length human THP2 using L-Trp as substrate assessed as formation of 5-HTP by measuring fluorescent property	ic50	0.0300	uM
3-ethyl-7-[[4-(1-methylpyrazol-3-yl)phenyl]methyl]-8-(5,6,7,8-tetrahydroimidazo[1,2-a]pyridin-2-ylmethyl)purine-2,6-dione	2021089: Inhibition of recombinant MBP-tagged full length human THP2 using L-Trp as substrate assessed as formation of 5-HTP by measuring fluorescent property	ic50	0.0300	uM
7-(1,3-benzodioxol-5-ylmethyl)-3-ethyl-8-(imidazo[1,2-a]pyridin-2-ylmethyl)purine-2,6-dione	2021089: Inhibition of recombinant MBP-tagged full length human THP2 using L-Trp as substrate assessed as formation of 5-HTP by measuring fluorescent property	ic50	0.0300	uM
3-ethyl-8-(5,6,7,8-tetrahydroimidazo[1,2-a]pyridin-2-ylmethyl)-7-[[4-(1,2,4-triazol-1-yl)phenyl]methyl]purine-2,6-dione	2021089: Inhibition of recombinant MBP-tagged full length human THP2 using L-Trp as substrate assessed as formation of 5-HTP by measuring fluorescent property	ic50	0.0310	uM
7-(cyclobutylmethyl)-3-ethyl-8-[(2-methylimidazo[2,1-b][1,3]thiazol-6-yl)methyl]purine-2,6-dione	2021089: Inhibition of recombinant MBP-tagged full length human THP2 using L-Trp as substrate assessed as formation of 5-HTP by measuring fluorescent property	ic50	0.0310	uM
7-[[4-(3,3-difluoroazetidin-1-yl)phenyl]methyl]-3-ethyl-8-(5,6,7,8-tetrahydroimidazo[1,2-a]pyridin-2-ylmethyl)purine-2,6-dione	2021089: Inhibition of recombinant MBP-tagged full length human THP2 using L-Trp as substrate assessed as formation of 5-HTP by measuring fluorescent property	ic50	0.0320	uM
7-(cyclobutylmethyl)-3-ethyl-8-(5,6,7,8-tetrahydroimidazo[1,2-a]pyridin-2-ylmethyl)purine-2,6-dione	2021089: Inhibition of recombinant MBP-tagged full length human THP2 using L-Trp as substrate assessed as formation of 5-HTP by measuring fluorescent property	ic50	0.0320	uM
3-ethyl-7-(3-methylbut-2-enyl)-8-[(2-methylimidazo[2,1-b][1,3]thiazol-6-yl)methyl]purine-2,6-dione	2021089: Inhibition of recombinant MBP-tagged full length human THP2 using L-Trp as substrate assessed as formation of 5-HTP by measuring fluorescent property	ic50	0.0320	uM
7-[(3,5-dimethylphenyl)methyl]-3-ethyl-8-[(2-methylimidazo[2,1-b][1,3]thiazol-6-yl)methyl]purine-2,6-dione	2021089: Inhibition of recombinant MBP-tagged full length human THP2 using L-Trp as substrate assessed as formation of 5-HTP by measuring fluorescent property	ic50	0.0340	uM
3-ethyl-7-[[4-(3-methoxyazetidin-1-yl)phenyl]methyl]-8-(5,6,7,8-tetrahydroimidazo[1,2-a]pyridin-2-ylmethyl)purine-2,6-dione	2021089: Inhibition of recombinant MBP-tagged full length human THP2 using L-Trp as substrate assessed as formation of 5-HTP by measuring fluorescent property	ic50	0.0350	uM
N-[4-[[3-ethyl-2,6-dioxo-8-(5,6,7,8-tetrahydroimidazo[1,2-a]pyridin-2-ylmethyl)purin-7-yl]methyl]phenyl]acetamide	2021089: Inhibition of recombinant MBP-tagged full length human THP2 using L-Trp as substrate assessed as formation of 5-HTP by measuring fluorescent property	ic50	0.0360	uM
ethyl 2-[3-ethyl-8-[(2-methylimidazo[2,1-b][1,3]thiazol-6-yl)methyl]-2,6-dioxopurin-7-yl]acetate	2021089: Inhibition of recombinant MBP-tagged full length human THP2 using L-Trp as substrate assessed as formation of 5-HTP by measuring fluorescent property	ic50	0.0370	uM
8-[(2-chloroimidazo[2,1-b][1,3]thiazol-6-yl)methyl]-3-ethyl-7-(oxetan-3-ylmethyl)purine-2,6-dione	2021089: Inhibition of recombinant MBP-tagged full length human THP2 using L-Trp as substrate assessed as formation of 5-HTP by measuring fluorescent property	ic50	0.0370	uM
methyl 2-[4-[[3-ethyl-8-(imidazo[1,2-a]pyridin-2-ylmethyl)-2,6-dioxopurin-7-yl]methyl]phenyl]acetate	2021089: Inhibition of recombinant MBP-tagged full length human THP2 using L-Trp as substrate assessed as formation of 5-HTP by measuring fluorescent property	ic50	0.0380	uM
3-ethyl-7-(3-methoxypropyl)-8-[(2-methylimidazo[2,1-b][1,3]thiazol-6-yl)methyl]purine-2,6-dione	2021089: Inhibition of recombinant MBP-tagged full length human THP2 using L-Trp as substrate assessed as formation of 5-HTP by measuring fluorescent property	ic50	0.0380	uM

CTD chemical–gene interactions

16 total (human), top 16 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, decreases methylation, affects methylation	3
methyleugenol	decreases expression	1
perfluorooctanoic acid	affects cotreatment, decreases expression	1
benzo(e)pyrene	increases methylation	1
perfluorooctane sulfonic acid	affects cotreatment, decreases expression	1
CGP 52608	affects binding, increases reaction	1
perfluorohexanesulfonic acid	affects cotreatment, decreases expression	1
Fluoxetine	affects response to substance	1
Methapyrilene	increases methylation	1
N-Nitrosopyrrolidine	decreases expression	1
Phthalic Acids	increases methylation	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	affects expression	1
8-Bromo Cyclic Adenosine Monophosphate	increases expression	1
Aflatoxin B1	decreases methylation	1
Particulate Matter	increases methylation	1

ChEMBL screening assays

7 unique, capped per target: 6 binding, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1016552	Binding	Inhibition of TPH2 in human BON cells assessed as inhibition of serotonin biosynthesis	Modulation of peripheral serotonin levels by novel tryptophan hydroxylase inhibitors for the potential treatment of functional gastrointestinal disorders. — *J Med Chem*
CHEMBL4001818	ADMET	Inhibition of TPH2 (unknown origin)	Optimization of spirocyclic proline tryptophan hydroxylase-1 inhibitors. — *Bioorg Med Chem Lett*

Clinical trials (associated diseases)

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

showing 60 of 300 trials:

NCT	Phase	Status	Title
NCT00000375	Phase 4	COMPLETED	Continuation Electroconvulsive Therapy Vs Medication to Prevent Relapses in Patients With Major Depressive Disorder
NCT00049972	Phase 4	COMPLETED	Major Depressive Disorder Study In Adults
NCT00157547	Phase 4	COMPLETED	Quantitative EEG (QEEG) as a Predictor of Treatment Outcome in Depression
NCT00166114	Phase 4	COMPLETED	Depression, Epinephrine, and Platelet Function
NCT00177996	Phase 4	COMPLETED	Pharmacotherapy in Depression With Panic Spectrum
NCT00178074	Phase 4	COMPLETED	The Effects of Sleep Deprivation on Antidepressant Response
NCT00178100	Phase 4	COMPLETED	Paroxetine and Interpersonal Psychotherapy for Maintaining Health and Well-being in Elderly Individuals With Depression
NCT00182533	Phase 4	TERMINATED	Sertraline in Generalized Social Phobia With Co-Occurring Anxiety and Mood Disorders
NCT00186446	Phase 4	COMPLETED	Treatment of Nicotine Dependence and Acute Depression
NCT00188942	Phase 4	COMPLETED	A Neuroimaging Investigation of Brain Activity in Major Depressive Disorder and Bipolar Disorder
NCT00191932	Phase 4	COMPLETED	Switching to Duloxetine From Other Antidepressants
NCT00203723	Phase 4	TERMINATED	Use of Risperidone in ECT for Treatment Resistant Depression
NCT00208169	Phase 4	COMPLETED	Abilify Therapy for Reducing Comorbid Substance Abuse
NCT00208702	Phase 4	COMPLETED	Thyroid Medication and Antidepressants for Treating Major Depression
NCT00208715	Phase 4	COMPLETED	Provigil in Conjunction With SSRIs for the Treatment of Mild or Moderate Depression With Attendant Symptoms of Sleepiness and Fatigue.
NCT00209807	Phase 4	UNKNOWN	Effect of Escitalopram vs. Reboxetine on Gastro-intestinal Sensitivity of Patients With Major Depressive Disorder
NCT00222820	Phase 4	COMPLETED	Depression: The Search for Treatment-Relevant Phenotypes-Pilot Study
NCT00223197	Phase 4	COMPLETED	Pregnenolone Trial for Depression in Bipolar Disorders or Recurrent Major Depressive Disorder With Substance Abuse
NCT00226356	Phase 4	COMPLETED	Natural Supplements for Unipolar Depression
NCT00234195	Phase 4	COMPLETED	Wellbutrin XL, Major Depressive Disorder and Breast Cancer
NCT00269334	Phase 4	UNKNOWN	Clinical Pharmacogenomics of Antidepressant Response
NCT00291239	Phase 4	UNKNOWN	Effect of Partial Sleep Deprivation on Cognition and Cytokines in Individuals With Major Depression
NCT00296686	Phase 4	TERMINATED	Sequential Tranylcypromine (TC), TC + Dextroamphetamine and TC + Triiodothyronine for Refractory Depression
NCT00296712	Phase 4	COMPLETED	Are Two Antidepressants a Good Initial Treatment for Depression?
NCT00296777	Phase 4	COMPLETED	Treatment of Depression Following Multiple Brain Tests
NCT00313417	Phase 4	TERMINATED	Creatine as a New Therapeutic Strategy in Depression
NCT00316160	Phase 4	COMPLETED	Sexual Functioning Study With Antidepressants
NCT00321152	Phase 4	COMPLETED	A Study of 6(S)-5-MTHF Among Serotonin Reuptake Inhibitor(SSRI)-Resistant Outpatients With Major Depressive Disorder (MDD)
NCT00330174	Phase 4	COMPLETED	Acamprosate in Alcoholics With Comorbid Anxiety or Depression
NCT00335205	Phase 4	UNKNOWN	A Placebo Controlled Trial of the Dopamine D-2 Receptor Agonist Ropinirole in Treatment of 60 Patients With Refractory Bipolar Depression.
NCT00353028	Phase 4	COMPLETED	Fluvoxamine Maleate in the Treatment of Depression/Depressive State : A Post-marketing Clinical Study in Children and Adolescents
NCT00357045	Phase 4	COMPLETED	Antidepressant Prophylaxis for Interferon-Induced Depression: Efficacy of Paroxetine
NCT00374426	Phase 4	COMPLETED	Preventing Depression Recurrence in Diabetes
NCT00384436	Phase 4	COMPLETED	Fixed Dose Comparison of Escitalopram to an Active Comparator in Severely Depressed Patients
NCT00404755	Phase 4	COMPLETED	Dichotic Listening as a Predictor of Medication Response in Depression
NCT00406848	Phase 4	COMPLETED	A Study Comparing the Efficacy and Safety of Duloxetine and Placebo for the Treatment of Depression in Elderly Patients
NCT00419003	Phase 4	COMPLETED	Research Study for Major Depressive Disorder: Investigation of Glutamate Medications
NCT00422162	Phase 4	COMPLETED	A Study Evaluating Duloxetine in Patients Hospitalized for Severe Depression
NCT00427128	Phase 4	COMPLETED	Prozac Treatment of Major Depression: Discontinuation Study
NCT00437125	Phase 4	COMPLETED	Study on the Tolerability of Duloxetine in Depressed Patients With Parkinson’s Disease
NCT00442481	Phase 4	UNKNOWN	Escitalopram and Sleep Architecture in Patients With Major Depressive Disorder
NCT00452543	Phase 4	COMPLETED	Acamprosate Added to Escitalopram and Behavioral Treatment for Comorbid Depression and Alcoholism
NCT00464711	Phase 4	COMPLETED	Brain GABA Levels and Treatment Response in Major Depressive Disorder
NCT00474708	Phase 4	COMPLETED	Study Comparing the Efficacy of Venlafaxine XR Vs. SSRIs and Conventional Antidepressants in Depressed Patients
NCT00479726	Phase 4	COMPLETED	Lilly’s Emotional and Physical Symptoms of Depression Study (LEAPS)
NCT00517985	Phase 4	COMPLETED	Duloxetine for Perimenopausal Depression
NCT00518986	Phase 4	COMPLETED	Efficacy and Safety of Armodafinil for Adults With Excessive Sleepiness Obstructive Sleep Apnea/Hypopnea and Depression
NCT00519428	Phase 4	COMPLETED	Does Dual Therapy Hasten Antidepressant Response?
NCT00531895	Phase 4	COMPLETED	An Open Trial of Duloxetine on Comorbid Major Depression and Chronic Headache
NCT00531947	Phase 4	COMPLETED	Phase IV:Safety and Efficacy of EMSAM in Adolescents With Major Depression
NCT00532480	Phase 4	COMPLETED	Study of Brain Response to Emotional Pictures Using a fMRI While on Duloxetine
NCT00536471	Phase 4	COMPLETED	A Study Comparing Duloxetine and Placebo in Assessing Energy and Vitality in Major Depressive Disorder (MDD) Patients
NCT00590863	Phase 4	COMPLETED	Combining Medications to Enhance Depression Outcomes
NCT00592384	Phase 4	COMPLETED	Project to Improve Symptoms and Mood in People With Spinal Cord Injury
NCT00595699	Phase 4	COMPLETED	Escitalopram Treatment of Major Depression in Patients With Temporal Lobe Epilepsy
NCT00608543	Phase 4	COMPLETED	Aripiprazole Augmentation of SSRI Therapy in Treatment Refractory Depression
NCT00628914	Phase 4	UNKNOWN	Brain Mechanisms and Targeting Insomnia in Major Depression
NCT00650897	Phase 4	UNKNOWN	Efficacy Study of Escitalopram for Depression in Patients With Diabetes
NCT00660062	Phase 4	TERMINATED	Relapse Prevention With Escitalopram or Nortriptyline Following Electro-Convulsive Treatment (DUAG-7)
NCT00675896	Phase 4	COMPLETED	A Study of Quetiapine Fumarate Sustained Release in Major Depression With Comorbid Fibromyalgia Syndrome

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for TPH2 across ~30M SureChEMBL compounds — explore on Sugi Predict.