TYK2

Summary

TYK2 (tyrosine kinase 2, HGNC:12440) is a protein-coding gene on chromosome 19p13.2, encoding Non-receptor tyrosine-protein kinase TYK2 (P29597). Tyrosine kinase of the non-receptor type involved in numerous cytokines and interferons signaling, which regulates cell growth, development, cell migration, innate and adaptive immunity.

This gene encodes a member of the tyrosine kinase and, more specifically, the Janus kinases (JAKs) protein families. This protein associates with the cytoplasmic domain of type I and type II cytokine receptors and promulgate cytokine signals by phosphorylating receptor subunits. It is also a component of both the type I and type III interferon signaling pathways. As such, it may play a role in anti-viral immunity. A mutation in this gene has been associated with Immunodeficiency 35.

Source: NCBI Gene 7297 — RefSeq curated summary.

At a glance

• Gene–disease (curated): immunodeficiency 35 (Strong, GenCC)
• GWAS associations: 56
• Clinical variants (ClinVar): 1,133 total — 29 pathogenic, 19 likely-pathogenic
• Phenotypes (HPO): 7
• Druggable target: yes — 72 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_003331

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12440
Approved symbol	TYK2
Name	tyrosine kinase 2
Location	19p13.2
Locus type	gene with protein product
Status	Approved
Aliases	JTK1
Ensembl gene	ENSG00000105397
Ensembl biotype	protein_coding
OMIM	176941
Entrez	7297

Gene structure

Transcript identifiers

Ensembl transcripts: 45 — 19 protein_coding, 11 retained_intron, 10 nonsense_mediated_decay, 5 protein_coding_CDS_not_defined

ENST00000524462, ENST00000524470, ENST00000525220, ENST00000525621, ENST00000525824, ENST00000525976, ENST00000527481, ENST00000529317, ENST00000529370, ENST00000529739, ENST00000530220, ENST00000530560, ENST00000530829, ENST00000531620, ENST00000531836, ENST00000533334, ENST00000534228, ENST00000699354, ENST00000699355, ENST00000699356, ENST00000699357, ENST00000699358, ENST00000699359, ENST00000699360, ENST00000699361, ENST00000699362, ENST00000699363, ENST00000699364, ENST00000699365, ENST00000699366, ENST00000699367, ENST00000699368, ENST00000699369, ENST00000699370, ENST00000699371, ENST00000907161, ENST00000907162, ENST00000907163, ENST00000913938, ENST00000955973, ENST00000955974, ENST00000955975, ENST00000955976, ENST00000955977, ENST00000955978

RefSeq mRNA: 13 — MANE Select: NM_003331 NM_001385197, NM_001385198, NM_001385199, NM_001385200, NM_001385201, NM_001385202, NM_001385203, NM_001385204, NM_001385205, NM_001385206, NM_001385207, NM_001406461, NM_003331

CCDS: CCDS12236, CCDS92513

Canonical transcript exons

ENST00000525621 — 25 exons

Exon	Start	End
ENSE00000676182	10357764	10357918
ENSE00000676185	10361511	10361598
ENSE00000676187	10362078	10362181
ENSE00000676188	10362264	10362456
ENSE00000676189	10362549	10362657
ENSE00000676190	10364614	10364771
ENSE00000676191	10364851	10365048
ENSE00000676192	10365517	10365898
ENSE00000676195	10368055	10368202
ENSE00000676198	10368295	10368418
ENSE00002169799	10380380	10380572
ENSE00002178984	10379615	10379779
ENSE00002180282	10378214	10378426
ENSE00002783874	10354042	10354234
ENSE00003479701	10366417	10366580
ENSE00003489148	10361770	10361955
ENSE00003497765	10358003	10358138
ENSE00003516462	10352926	10353098
ENSE00003528248	10354512	10354609
ENSE00003590014	10356568	10356718
ENSE00003595926	10353528	10353646
ENSE00003644197	10359175	10359302
ENSE00003646624	10350533	10350968
ENSE00003656906	10351052	10351162
ENSE00003785601	10352434	10352551

Expression profiles

Bgee: expression breadth ubiquitous, 288 present calls, max score 99.24.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 22.2469 / max 490.8687, expressed in 1814 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
179123	13.7255	1802
179124	7.4059	1745
179119	0.4025	153
179122	0.3533	119
179118	0.1656	80
179120	0.1047	39
179117	0.0894	60

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	99.24	gold quality
right hemisphere of cerebellum	UBERON:0014890	98.28	gold quality
adenohypophysis	UBERON:0002196	98.20	gold quality
cerebellar hemisphere	UBERON:0002245	98.08	gold quality
metanephros cortex	UBERON:0010533	98.08	gold quality
cerebellar cortex	UBERON:0002129	97.98	gold quality
right lobe of thyroid gland	UBERON:0001119	97.97	gold quality
spleen	UBERON:0002106	97.94	gold quality
small intestine Peyer’s patch	UBERON:0003454	97.90	gold quality
right uterine tube	UBERON:0001302	97.89	gold quality
right lobe of liver	UBERON:0001114	97.85	gold quality
nerve	UBERON:0001021	97.84	gold quality
tibial nerve	UBERON:0001323	97.84	gold quality
right ovary	UBERON:0002118	97.84	gold quality
apex of heart	UBERON:0002098	97.79	gold quality
left lobe of thyroid gland	UBERON:0001120	97.78	gold quality
upper lobe of left lung	UBERON:0008952	97.74	gold quality
endocervix	UBERON:0000458	97.53	gold quality
left ovary	UBERON:0002119	97.49	gold quality
mucosa of transverse colon	UBERON:0004991	97.45	gold quality
left uterine tube	UBERON:0001303	97.41	gold quality
pituitary gland	UBERON:0000007	97.36	gold quality
minor salivary gland	UBERON:0001830	97.35	gold quality
body of uterus	UBERON:0009853	97.34	gold quality
monocyte	CL:0000576	97.33	gold quality
right lung	UBERON:0002167	97.32	gold quality
mucosa of stomach	UBERON:0001199	97.26	gold quality
body of stomach	UBERON:0001161	97.14	gold quality
skin of leg	UBERON:0001511	97.12	gold quality
leukocyte	CL:0000738	97.11	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.29

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): STAT1, STAT3

Literature-anchored findings (GeneRIF, showing 40)

• Data show that Tyk2 tyrosine kinase is essential for stable cell surface expression of IFNAR1. (PMID:12554654)
• evidence that the small GTPases RhoA and Rac1, but not Cdc42, are directly associated with Tyk2 and PI3-K in an uPA/uPAR-dependent fashion and are necessary to mediate the uPA/uPAR-directed migration via the Tyk2/PI3-K signalling complex in human VSMC (PMID:12719789)
• Catalytically active Tyk2 is necessary for Janus kinase 2 phosphorylation and association with the platelet-activating factor receptor. (PMID:14500680)
• In the IFN signaling pathway leading to STAT activation, both JAK1 and TYK2 are essential, whereas NF-kappaB activation requires only TYK2. (PMID:15883164)
• Janus kinase Tyk2 and the transcription factor Stat3 serve as downstream components in the signaling cascade resulting in upregulation of C5aR expression (PMID:15944400)
• mutations in the JAK1 and Tyk2 genes may be identified as initial molecular defects in human cancers and autoimmune diseases (PMID:16239216)
• catalytic activation of Tyk2 is not essential for IFNAR1 internalization, but is required for ligand-induced IFNAR1 serine phosphorylation, ubiquitination and efficient lysosomal proteolysis (PMID:16551269)
• Tyk2 mutation is not associated with essential thrombocythaemia (PMID:17011030)
• study showed association to systemic lupus erythematosus from individual SNPs and haplotypes in TYK2 (PMID:17384181)
• suggest a novel function for Tyk2 as an important modulator of the urokinase-directed vascular smooth muscle cell functional behaviour at the place of injury (PMID:17548050)
• These results suggest that Tyk2 signaling in prostate cancer cells facilitate invasion of these cells, and interference with this signaling may be a potential therapeutic pathway. (PMID:17920038)
• protein tyrosine kinase TYK2 genes were found significantly upregulated in the cases with progressive sarcoidosis. (PMID:17937105)
• The Stat3-activating Tyk2 V678F mutant does not up-regulate signaling through the type I interferon receptor but confers ligand hypersensitivity to a homodimeric receptor (PMID:18456658)
• Tyk2 contributes to both the regulation of total IFNAR1 levels as well as the regulation of the cell surface density of this receptor chain. (PMID:18474601)
• when type I IFN is added to primary human fibroblasts following MV infection, the tyrosine phosphorylation of the Janus kinase Tyk2 is specifically blocked, thereby preventing the subsequent activation of downstream STAT1 and STAT2 (PMID:19254804)
• TYK2 may be a multiple sclerosis susceptibility factor (PMID:19293837)
• TYK2 is not a genetic risk factor for systemic lupus erythematosus in a Japanese population suggesting that there is an ethnic difference in the susceptibility genes for this disease. (PMID:19440814)
• The IFN pathway genes IRF5 and TYK2 may act epistatically in increasing risk for systemic lupus erythematosus (PMID:19567624)
• TYK2 and STAT3 are genetic determinants of Crohn’s disease in the Japanese population. (PMID:19653082)
• Studies have demonstrated that mutations in STAT3 and TYK2 genes result in Hyper-IgE syndrome (HIES. (PMID:19717292)
• rs2304256 associated with increased risk of discoid lupus erythematosus (PMID:19758313)
• Single-nucleotide polymorphism in TYK2 gene is confirmed to be associated with multiple sclerosis. (PMID:19888296)
• Studies indicate that the highest T1D association was at marker rs2304256 (odds ratio (OR) = 0.86; 95%CI = 0.82-0.90) in the TYK2 gene 19p13.2See TYK2 gene at chromosome 19p13.2. (PMID:19966805)
• Here, the authors report the crystal structures of TYK2, a first in class structure, and JAK3 in complex with PAN-JAK inhibitors CP-690550 and CMP-6, both of which bind in the ATP-binding cavities of both JAK isozymes. (PMID:20478313)
• Siva-1 forms a functional complex with Tyk2 and participates in the transduction of signals that inhibit B lymphocyte growth. (PMID:20727854)
• This meta-analysis demonstrates that autoimmune and inflammatory diseases is associated with TYK2 gene rs34536443 and rs2304256 polymorphisms, but not rs280523, rs280519, rs12720270 and rs12720356. (PMID:21140222)
• Tyk2 deficiency and clinical manifestations of hyper IgE syndromes (Review) (PMID:21178271)
• Data suggest that TYK2 polymorphisms were not associated with systemic lupus erythematosus in Hong Kong Chinese, but that rs2304256 and rs12720270 may be associated with photosensitivity and discoid rash. (PMID:21196586)
• The rs34536443 variant effect on multiple sclerosis susceptibility might be mediated by deviating T lymphocyte differentiation toward a Th2 phenotype. (PMID:21354972)
• The consequent effect of SOCS1 inhibition of Tyk2 not only results in a reduced IFN response because of inhibition of Tyk2 kinase-mediated STAT signaling but also negatively impacts IFNAR1 surface expression, which is stabilized by Tyk2. (PMID:21757742)
• infection of airway epithelial cells with hMPV decreased cellular level of Janus tyrosine kinase (Jak1) and tyrosine kinase 2 (Tyk2) (PMID:21949722)
• Association analysis identified five SLE susceptibility genes reaching genome-wide levels of significance : NCF2 ,IKZF1 ,IRF8 ,IFIH1 , and TYK2 (PMID:22046141)
• data highlight the role of TYK2 downregulation in breast cancer cell de-differentitation and initiation of regional metastasis (PMID:22116632)
• Studied the doubly tagged full-length construct, H6-FL-TYK-2-FLAG. In the presence of ATP and a peptide substrate, H6-FL-TYK-2-FLAG showed a marked lag in phosphopeptide product formation. TYK-2 KD showed no such lag. (PMID:22486643)
• In our pilot study, we discovered significant changes in methylation patterns of genes IL-7, IL-13, IL-17C and TYK2 between henodialysis patients and healthy subjects (PMID:22506826)
• The rs6445975 polymorphism of phox homology domain containing serine/threonine kinase and the rs2304256 polymorphism of tyrosine kinase 2 are associated with the development of systemic lupus erythematosus in Europeans (PMID:22592861)
• This study demonistrated that Rs55762744 is a rare variant of modest effect on multiple sclerosis risk affecting a subset of patients. (PMID:22744673)
• The most associated variant in primary biliary cirrhosis was in chromosome 19, a low-frequency nonsynonymous single nucleotide polymorphism in TYK2. (PMID:22961000)
• TYK2 rs34536443 polymorphism is associated with a decreased susceptibility to endometriosis-related infertility. (PMID:23000200)
• Two rare autoimmune disease-associated Tyk2 variants are catalytically impaired but signaling competent. (PMID:23359498)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	tyk2	ENSDARG00000020326
mus_musculus	Tyk2	ENSMUSG00000032175
rattus_norvegicus	Tyk2	ENSRNOG00000032948

Paralogs (32): FGR (ENSG00000000938), MATK (ENSG00000007264), BTK (ENSG00000010671), FYN (ENSG00000010810), STYK1 (ENSG00000060140), TNK2 (ENSG00000061938), TXK (ENSG00000074966), JAK2 (ENSG00000096968), ABL1 (ENSG00000097007), PTK6 (ENSG00000101213), HCK (ENSG00000101336), BMX (ENSG00000102010), CSK (ENSG00000103653), JAK3 (ENSG00000105639), FRK (ENSG00000111816), ITK (ENSG00000113263), ZAP70 (ENSG00000115085), PTK2B (ENSG00000120899), SRMS (ENSG00000125508), TEC (ENSG00000135605), BLK (ENSG00000136573), ABL2 (ENSG00000143322), FER (ENSG00000151422), JAK1 (ENSG00000162434), SYK (ENSG00000165025), PTK2 (ENSG00000169398), TNK1 (ENSG00000174292), YES1 (ENSG00000176105), FES (ENSG00000182511), LCK (ENSG00000182866), SRC (ENSG00000197122), LYN (ENSG00000254087)

Protein

Protein identifiers

Non-receptor tyrosine-protein kinase TYK2 — P29597 (reviewed: P29597)

All UniProt accessions (18): P29597, A0A8V8TN50, A0A8V8TN55, A0A8V8TN89, A0A8V8TN95, A0A8V8TNM9, A0A8V8TPH2, A0A8V8TPJ0, A0A8V8TPJ3, A0A8V8TPX5, E9PM19, E9PQE9, E9PQL2, H0YCT7, H0YE24, H0YE41, K7EJR6, K7EM33

UniProt curated annotations — full annotation on UniProt →

Function. Tyrosine kinase of the non-receptor type involved in numerous cytokines and interferons signaling, which regulates cell growth, development, cell migration, innate and adaptive immunity. Plays both structural and catalytic roles in numerous interleukins and interferons (IFN-alpha/beta) signaling. Associates with heterodimeric cytokine receptor complexes and activates STAT family members including STAT1, STAT3, STAT4 or STAT6. The heterodimeric cytokine receptor complexes are composed of (1) a TYK2-associated receptor chain (IFNAR1, IL12RB1, IL10RB or IL13RA1), and (2) a second receptor chain associated either with JAK1 or JAK2. In response to cytokine-binding to receptors, phosphorylates and activates receptors (IFNAR1, IL12RB1, IL10RB or IL13RA1), creating docking sites for STAT members. In turn, recruited STATs are phosphorylated by TYK2 (or JAK1/JAK2 on the second receptor chain), form homo- and heterodimers, translocate to the nucleus, and regulate cytokine/growth factor responsive genes. Negatively regulates STAT3 activity by promototing phosphorylation at a specific tyrosine that differs from the site used for signaling.

Subunit / interactions. Interacts (via FERM domain) with JAKMIP1. Interacts with PIK3R1; this interaction is important for cell migration. Interacts with MPL/TPOR. (Microbial infection) Interacts with Epstein-Barr virus protein LMP1; this interaction inhibits TYK2-mediated interferon signaling. (Microbial infection) Interacts with papillomavirus-18 protein E6; this interaction impairs JAK-STAT activation by interferon-alpha. (Microbial infection) Interacts with Epstein-Barr virus (EBV) tegument protein BGLF2; this interaction participates in the inhibition of type I IFN signaling by the virus.

Tissue specificity. Observed in all cell lines analyzed. Expressed in a variety of lymphoid and non-lymphoid cell lines.

Post-translational modifications. Phosphorylated. Phosphorylation by JAK1 at Tyr-1054 and Tyr-1055 induces kinase activation.

Disease relevance. Immunodeficiency 35 (IMD35) [MIM:611521] A primary immunodeficiency characterized by recurrent skin abscesses, pneumonia, and highly elevated serum IgE. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. The protein kinase 1 domain (also termed pseudokinase domain) mediates autoinhibition of the TYK2 kinase domain.

Similarity. Belongs to the protein kinase superfamily. Tyr protein kinase family. JAK subfamily.

RefSeq proteins (13): NP_001372126, NP_001372127, NP_001372128, NP_001372129, NP_001372130, NP_001372131, NP_001372132, NP_001372133, NP_001372134, NP_001372135, NP_001372136, NP_001393390, NP_003322* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000299	FERM_domain	Domain
IPR000719	Prot_kinase_dom	Domain
IPR000980	SH2	Domain
IPR001245	Ser-Thr/Tyr_kinase_cat_dom	Domain
IPR008266	Tyr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR016045	Tyr_kinase_non-rcpt_TYK2_N	Domain
IPR016251	Tyr_kinase_non-rcpt_Jak/Tyk2	Family
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR019749	Band_41_domain	Domain
IPR020635	Tyr_kinase_cat_dom	Domain
IPR035963	FERM_2	Homologous_superfamily
IPR036860	SH2_dom_sf	Homologous_superfamily
IPR041046	FERM_F2	Domain
IPR041155	FERM_F1	Domain
IPR041381	JAK1-3/TYK2_PHL_dom	Domain
IPR051286	JAK	Family

Pfam: PF07714, PF17887, PF18377, PF18379, PF21990

Enzyme classification (BRENDA):

• EC 2.7.10.2 — non-specific protein-tyrosine kinase (BRENDA: 41 organisms, 396 substrates, 479 inhibitors, 43 Km, 32 kcat entries)

Substrate kinetics (BRENDA)

6 substrates with measured Km, best-characterized 6. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.014–17.64	12
[KDSRC KINASE]-L-TYROSINE	0.0057–0.24	12
POLY(GLU4-TYR)	0.018–0.659	10
EEEEYIQ[DP]-8-HYDROXY-5-(N,N-DIMETHYLSULFONAMIDO	0.057	1
S1 PEPTIDE	0.037	1
EEEEY	—	0

Catalyzed reactions (Rhea), 1 shown:

• L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+) (RHEA:10596)

UniProt features (143 total): helix 46, strand 41, sequence variant 14, turn 11, modified residue 7, mutagenesis site 6, sequence conflict 6, domain 4, binding site 2, region of interest 2, compositionally biased region 2, chain 1, active site 1

Structure

Experimental structures (PDB)

52 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
3LXP	X-RAY DIFFRACTION	1.65
8S99	X-RAY DIFFRACTION	1.71
4WOV	X-RAY DIFFRACTION	1.8
8S9A	X-RAY DIFFRACTION	1.83
8S98	X-RAY DIFFRACTION	1.87
5C03	X-RAY DIFFRACTION	1.9
5TKD	X-RAY DIFFRACTION	1.92
6NZE	X-RAY DIFFRACTION	1.96
8TB6	X-RAY DIFFRACTION	1.96
6AAM	X-RAY DIFFRACTION	1.98
4PO6	X-RAY DIFFRACTION	1.99
3NZ0	X-RAY DIFFRACTION	2
4GIH	X-RAY DIFFRACTION	2
6DBK	X-RAY DIFFRACTION	2
4GVJ	X-RAY DIFFRACTION	2.03
7UYU	X-RAY DIFFRACTION	2.05
6VNS	X-RAY DIFFRACTION	2.09
6NZQ	X-RAY DIFFRACTION	2.11
7AX4	X-RAY DIFFRACTION	2.12
7UYT	X-RAY DIFFRACTION	2.14
3ZON	X-RAY DIFFRACTION	2.15
5C01	X-RAY DIFFRACTION	2.15
6NSL	X-RAY DIFFRACTION	2.15
6VNV	X-RAY DIFFRACTION	2.15
6X8F	X-RAY DIFFRACTION	2.15
7UYR	X-RAY DIFFRACTION	2.15
7UYS	X-RAY DIFFRACTION	2.15
8EXN	X-RAY DIFFRACTION	2.15
4PY1	X-RAY DIFFRACTION	2.16
6VNX	X-RAY DIFFRACTION	2.18

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P29597-F1	82.69	0.53

Functional residue map

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

Catalytic / active sites (1): 1023 (proton acceptor)

Ligand- & substrate-binding residues (2): 903–911; 930

Post-translational modifications (7): 292, 499, 525, 604, 884, 1054, 1055

Mutagenesis-validated functional residues (6):

Position	Phenotype
930	complete loss of catalytic activity.
1023	complete loss of catalytic activity.
1054	reduces basal catalytic activity and abolishes ifn-dependent activation.
1055	reduces basal catalytic activity and abolishes ifn-dependent activation.
1145	does not affect phosphorylation state and enzymatic activity.
1176	does not affect phosphorylation state and enzymatic activity.

Function

Pathways and Gene Ontology

Reactome pathways

21 pathways

ID	Pathway
R-HSA-1059683	Interleukin-6 signaling
R-HSA-110056	MAPK3 (ERK1) activation
R-HSA-112411	MAPK1 (ERK2) activation
R-HSA-449836	Other interleukin signaling
R-HSA-6783783	Interleukin-10 signaling
R-HSA-6785807	Interleukin-4 and Interleukin-13 signaling
R-HSA-6788467	IL-6-type cytokine receptor ligand interactions
R-HSA-8854691	Interleukin-20 family signaling
R-HSA-8984722	Interleukin-35 Signalling
R-HSA-9020591	Interleukin-12 signaling
R-HSA-9020933	Interleukin-23 signaling
R-HSA-9020956	Interleukin-27 signaling
R-HSA-909733	Interferon alpha/beta signaling
R-HSA-912694	Regulation of IFNA/IFNB signaling
R-HSA-9674555	Signaling by CSF3 (G-CSF)
R-HSA-9679191	Potential therapeutics for SARS
R-HSA-9705462	Inactivation of CSF3 (G-CSF) signaling
R-HSA-9705671	SARS-CoV-2 activates/modulates innate and adaptive immune responses
R-HSA-9725370	Signaling by ALK fusions and activated point mutants
R-HSA-9833109	Evasion by RSV of host interferon responses
R-HSA-9958825	Activation of STAT3 by cadherin engagement

MSigDB gene sets: 318 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_UP, GOBP_REGULATION_OF_CELL_ACTIVATION, REACTOME_INTERLEUKIN_6_SIGNALING, MYAATNNNNNNNGGC_UNKNOWN, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_REGULATION_OF_ALPHA_BETA_T_CELL_ACTIVATION, GNF2_BNIP2, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_RESPONSE_TO_PEPTIDE, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_RESPONSE_TO_TYPE_I_INTERFERON, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, THEILGAARD_NEUTROPHIL_AT_SKIN_WOUND_DN, RIZKI_TUMOR_INVASIVENESS_3D_DN

GO Biological Process (28): protein phosphorylation (GO:0006468), immune response (GO:0006955), cell surface receptor signaling pathway via JAK-STAT (GO:0007259), cell population proliferation (GO:0008283), cytokine-mediated signaling pathway (GO:0019221), cell differentiation (GO:0030154), positive regulation of type II interferon production (GO:0032729), positive regulation of interleukin-17 production (GO:0032740), positive regulation of natural killer cell proliferation (GO:0032819), intracellular signal transduction (GO:0035556), interleukin-12-mediated signaling pathway (GO:0035722), interleukin-23-mediated signaling pathway (GO:0038155), type III interferon-mediated signaling pathway (GO:0038196), positive regulation of T cell proliferation (GO:0042102), positive regulation of receptor signaling pathway via JAK-STAT (GO:0046427), positive regulation of NK T cell proliferation (GO:0051142), type II interferon-mediated signaling pathway (GO:0060333), type I interferon-mediated signaling pathway (GO:0060337), growth hormone receptor signaling pathway via JAK-STAT (GO:0060397), cellular response to virus (GO:0098586), interleukin-10-mediated signaling pathway (GO:0140105), positive regulation of protein localization to nucleus (GO:1900182), positive regulation of T-helper 17 type immune response (GO:2000318), regulation of transcription by RNA polymerase II (GO:0006357), regulation of cell-cell adhesion (GO:0022407), regulation of receptor signaling pathway via JAK-STAT (GO:0046425), regulation of alpha-beta T cell activation (GO:0046634), regulation of multicellular organismal process (GO:0051239)

GO Molecular Function (9): protein tyrosine kinase activity (GO:0004713), non-membrane spanning protein tyrosine kinase activity (GO:0004715), growth hormone receptor binding (GO:0005131), ATP binding (GO:0005524), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (13): nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), cytoplasmic side of plasma membrane (GO:0009898), extrinsic component of plasma membrane (GO:0019897), extrinsic component of cytoplasmic side of plasma membrane (GO:0031234), interleukin-12 receptor complex (GO:0042022), signaling receptor complex (GO:0043235), extracellular exosome (GO:0070062), interleukin-23 receptor complex (GO:0072536), cytoskeleton (GO:0005856), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-12 pathways:

Category	Pathways
Signaling by Interleukins	4
Interleukin-12 family signaling	4
Interleukin-6 family signaling	2
RAF-independent MAPK1/3 activation	2
Interferon Signaling	1
Interferon alpha/beta signaling	1
Cytokine Signaling in Immune system	1
SARS-CoV Infections	1
Signaling by CSF3 (G-CSF)	1
SARS-CoV-2-host interactions	1
Signaling by ALK in cancer	1
RSV-host interactions	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
interferon-mediated signaling pathway	3
cellular anatomical structure	3
positive regulation of cytokine production	2
positive regulation of lymphocyte proliferation	2
intracellular anatomical structure	2
cytokine-mediated signaling pathway	2
plasma membrane	2
plasma membrane signaling receptor complex	2
phosphorylation	1
protein modification process	1
immune system process	1
response to stimulus	1
cell surface receptor signaling pathway via STAT	1
cellular process	1
cell surface receptor signaling pathway	1
cellular response to cytokine stimulus	1
cellular developmental process	1
type II interferon production	1
regulation of type II interferon production	1
interleukin-17 production	1
regulation of interleukin-17 production	1
natural killer cell proliferation	1
positive regulation of natural killer cell activation	1
regulation of natural killer cell proliferation	1
signal transduction	1
cellular response to interleukin-12	1
cellular response to type III interferon	1
T cell proliferation	1
regulation of T cell proliferation	1
positive regulation of T cell activation	1
cell surface receptor signaling pathway via JAK-STAT	1
regulation of receptor signaling pathway via JAK-STAT	1
positive regulation of receptor signaling pathway via STAT	1
NK T cell proliferation	1
positive regulation of alpha-beta T cell proliferation	1
positive regulation of NK T cell activation	1
regulation of NK T cell proliferation	1
cellular response to type II interferon	1
cellular response to type I interferon	1
growth hormone receptor signaling pathway	1

Protein interactions and networks

STRING

3553 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TYK2	IFNAR1	P17181	997
TYK2	IL12RB1	P42701	997
TYK2	IFNAR2	P48551	995
TYK2	IL10RB	Q08334	994
TYK2	SOCS3	O14543	992
TYK2	SOCS1	O15524	991
TYK2	IFNA13	P01562	985
TYK2	JAK1	P23458	984
TYK2	IL13RA1	P78552	982
TYK2	JAK2	O60674	982
TYK2	IL6	P05231	972
TYK2	IL10RA	Q13651	970
TYK2	STAT2	P52630	965
TYK2	STAT3	P40763	960
TYK2	STAT1	P42224	953

IntAct

170 interactions, top by confidence:

A	B	Type	Score
CCM2	KRIT1	psi-mi:“MI:0914”(association)	0.960
IFT43	TULP3	psi-mi:“MI:0914”(association)	0.790
KHDRBS2	TYK2	psi-mi:“MI:0915”(physical association)	0.780
TYK2	KHDRBS2	psi-mi:“MI:0915”(physical association)	0.780
GMNN	MCIDAS	psi-mi:“MI:0914”(association)	0.770
STAT2	N	psi-mi:“MI:0915”(physical association)	0.760
STAT2	N	psi-mi:“MI:0914”(association)	0.760
FHL3	TYK2	psi-mi:“MI:0915”(physical association)	0.720
TYK2	FHL3	psi-mi:“MI:0915”(physical association)	0.720
TYK2	HNRNPK	psi-mi:“MI:0915”(physical association)	0.670
GPR156	PLD2	psi-mi:“MI:0914”(association)	0.640
LRRC46	TFPT	psi-mi:“MI:0914”(association)	0.640
TYK2	STAT2	psi-mi:“MI:0915”(physical association)	0.640
STAT2	TYK2	psi-mi:“MI:0915”(physical association)	0.640
KRT40	TYK2	psi-mi:“MI:0915”(physical association)	0.560
TRAF4	TYK2	psi-mi:“MI:0915”(physical association)	0.560
TYK2	TRAF4	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (209): TYK2 (Two-hybrid), TYK2 (Two-hybrid), TRAF4 (Two-hybrid), KRT40 (Two-hybrid), KHDRBS2 (Two-hybrid), SIVA1 (Two-hybrid), SIVA1 (Affinity Capture-Western), SIVA1 (Phenotypic Enhancement), TYK2 (Affinity Capture-Western), TYK2 (Affinity Capture-RNA), TYK2 (Affinity Capture-RNA), TYK2 (Affinity Capture-RNA), BAG2 (Affinity Capture-MS), CCT2 (Affinity Capture-MS), CCT3 (Affinity Capture-MS)

ESM2 similar proteins: A0A061IR73, A0A1B0GUU1, A6H687, A8MYJ7, B1WC39, D3ZVB0, E1BD59, G3MY25, G3MZC5, O75064, P07199, P27790, P29597, P48988, P52333, P52824, Q08DF2, Q0VCE3, Q13608, Q1JPD6, Q2VPB7, Q3TAP4, Q3U1Y4, Q3ZBE0, Q499M4, Q53EQ6, Q5JZY3, Q62137, Q63272, Q6B0B8, Q6DI92, Q6ZPS2, Q6ZS72, Q7TM95, Q80VI1, Q86UT6, Q8BYG9, Q8N9M5, Q8R5G7, Q8TE96

Diamond homologs: F1N9Y5, O12990, O19064, O42127, O54967, O60674, P00522, P00533, P00534, P00535, P06239, P07948, P07949, P08103, P08630, P08631, P0CY46, P11273, P11362, P13388, P16092, P18460, P18461, P21709, P21802, P21803, P21804, P22182, P22455, P22607, P23458, P24786, P25911, P29597, P35739, P42683, P42685, P42690, P43403, P43404

SIGNOR signaling

27 interactions.

A	Effect	B	Mechanism
IL13RA1	up-regulates	TYK2	binding
PTPN6	down-regulates	TYK2
IFNLR1	up-regulates	TYK2	binding
PTPN1	“down-regulates activity”	TYK2	dephosphorylation
TYK2	up-regulates	DUSP3	phosphorylation
TYK2	“up-regulates activity”	IFNAR1	phosphorylation
JAK1	up-regulates	TYK2	phosphorylation
IL15RA	up-regulates	TYK2
TYK2	up-regulates	STAT3	phosphorylation
IFNAR	“up-regulates activity”	TYK2	binding
TYK2	“up-regulates activity”	“ISGF3 complex”	phosphorylation
TYK2	“up-regulates activity”	STAT2	phosphorylation
TYK2	“up-regulates activity”	STAT4	phosphorylation
TYK2	“down-regulates activity”	KLF10	phosphorylation
TYK2	“up-regulates activity”	TYK2	phosphorylation
IL10RB	up-regulates	TYK2	binding
IFNB1	up-regulates	TYK2
IL23R	up-regulates	TYK2	binding
IL22RA1	up-regulates	TYK2	binding
PTPRC	“down-regulates activity”	TYK2	dephosphorylation
TYK2	“up-regulates activity”	STAT1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 126 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Potential therapeutics for SARS	7	11.6×	1e-03
Signaling by Interleukins	7	6.5×	8e-03
Cytokine Signaling in Immune system	9	5.3×	5e-03

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

1133 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	29
Likely pathogenic	19
Uncertain significance	500
Likely benign	431
Benign	76

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1069417	NM_003331.5(TYK2):c.2573C>G (p.Ser858Ter)	Pathogenic
1425910	NM_003331.5(TYK2):c.2393G>A (p.Trp798Ter)	Pathogenic
1459846	NC_000019.9:g.(?10463090)(10465305_?)del	Pathogenic
155930	NM_003331.5(TYK2):c.2303_2311del (p.Ser768_Glu771delinsTer)	Pathogenic
1703747	NM_003331.5(TYK2):c.2269C>G (p.Leu757Val)	Pathogenic
1703748	NM_003331.5(TYK2):c.3041T>C (p.Leu1014Pro)	Pathogenic
1703749	NM_003331.5(TYK2):c.1253C>A (p.Ser418Ter)	Pathogenic
1703750	NM_003331.5(TYK2):c.2395G>A (p.Gly799Arg)	Pathogenic
2022602	NM_003331.5(TYK2):c.1148dup (p.Thr384fs)	Pathogenic
224885	NM_003331.4(TYK2):c.3318_3319insC	Pathogenic
224886	NM_003331.5(TYK2):c.460G>T (p.Glu154Ter)	Pathogenic
224887	NM_003331.5(TYK2):c.149del (p.Ser50fs)	Pathogenic
224888	NM_003331.5(TYK2):c.1912C>T (p.Arg638Ter)	Pathogenic
225508	NM_003331.5(TYK2):c.209_212del (p.Cys70fs)	Pathogenic
2704548	NM_003331.5(TYK2):c.2488C>T (p.Gln830Ter)	Pathogenic
2739687	NM_003331.5(TYK2):c.1904dup (p.Glu636fs)	Pathogenic
2761990	NM_003331.5(TYK2):c.2920_2941del (p.Leu974fs)	Pathogenic
2764448	NM_003331.5(TYK2):c.424C>T (p.Gln142Ter)	Pathogenic
2911814	NM_003331.5(TYK2):c.463C>T (p.Gln155Ter)	Pathogenic
2971918	NM_003331.5(TYK2):c.1825C>T (p.Arg609Ter)	Pathogenic
3248457	NC_000019.9:g.(?10469831)(10469998_?)del	Pathogenic
3619403	NM_003331.5(TYK2):c.905del (p.Asp302fs)	Pathogenic
3659006	NM_003331.5(TYK2):c.2873_2874insTGTA (p.Ile959fs)	Pathogenic
3684066	NM_003331.5(TYK2):c.1507C>T (p.Arg503Ter)	Pathogenic
3720074	NM_003331.5(TYK2):c.3013C>T (p.Gln1005Ter)	Pathogenic
4722157	NM_003331.5(TYK2):c.3229_3230insC (p.Lys1077fs)	Pathogenic
4802964	NM_003331.5(TYK2):c.2739_2758dup (p.Asn920fs)	Pathogenic
4803568	NM_003331.5(TYK2):c.3133_3142del (p.Ala1045fs)	Pathogenic
4803569	NM_003331.5(TYK2):c.3130del (p.Gly1043_Leu1044insTer)	Pathogenic
1067902	NM_003331.5(TYK2):c.2047+1G>T	Likely pathogenic

SpliceAI

3896 predictions. Top by Δscore:

Variant	Effect	Δscore
19:10350969:C:CC	acceptor_gain	1.0000
19:10350969:CTAGA:C	acceptor_loss	1.0000
19:10352899:C:CA	donor_gain	1.0000
19:10352946:AT:A	donor_gain	1.0000
19:10352947:T:TA	donor_gain	1.0000
19:10352957:CG:C	donor_gain	1.0000
19:10352966:A:AC	donor_gain	1.0000
19:10352967:C:CC	donor_gain	1.0000
19:10353095:TGCC:T	acceptor_gain	1.0000
19:10353097:CC:C	acceptor_gain	1.0000
19:10353098:CC:C	acceptor_gain	1.0000
19:10353099:CTGGG:C	acceptor_loss	1.0000
19:10353651:C:CT	acceptor_gain	1.0000
19:10354038:CCACC:C	donor_loss	1.0000
19:10354040:A:AG	donor_loss	1.0000
19:10354066:A:AC	donor_gain	1.0000
19:10354067:C:CC	donor_gain	1.0000
19:10354230:TGACC:T	acceptor_gain	1.0000
19:10354231:GACC:G	acceptor_gain	1.0000
19:10354233:CC:C	acceptor_gain	1.0000
19:10354234:CC:C	acceptor_gain	1.0000
19:10354234:CCTGG:C	acceptor_loss	1.0000
19:10354235:C:CC	acceptor_gain	1.0000
19:10354236:T:A	acceptor_loss	1.0000
19:10354240:C:CT	acceptor_gain	1.0000
19:10354610:C:CC	acceptor_gain	1.0000
19:10356536:C:A	donor_gain	1.0000
19:10356562:GCTCA:G	donor_loss	1.0000
19:10356563:CTCAC:C	donor_loss	1.0000
19:10356564:TCACT:T	donor_loss	1.0000

AlphaMissense

7753 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:10354160:T:A	K930N	1.000
19:10354160:T:G	K930N	1.000
19:10352499:A:G	W1085R	0.999
19:10352499:A:T	W1085R	0.999
19:10352927:A:G	W1067R	0.999
19:10352927:A:T	W1067R	0.999
19:10353003:G:C	D1041E	0.999
19:10353003:G:T	D1041E	0.999
19:10353004:T:A	D1041V	0.999
19:10353004:T:G	D1041A	0.999
19:10353058:T:A	D1023V	0.999
19:10353058:T:G	D1023A	0.999
19:10353061:C:G	R1022P	0.999
19:10354161:T:A	K930I	0.999
19:10354226:G:C	F908L	0.999
19:10354226:G:T	F908L	0.999
19:10354228:A:G	F908L	0.999
19:10352518:G:C	F1078L	0.998
19:10352518:G:T	F1078L	0.998
19:10352520:A:G	F1078L	0.998
19:10353004:T:C	D1041G	0.998
19:10353005:C:G	D1041H	0.998
19:10353057:G:C	D1023E	0.998
19:10353057:G:T	D1023E	0.998
19:10353058:T:C	D1023G	0.998
19:10353598:A:T	L986H	0.998
19:10354162:T:C	K930E	0.998
19:10354162:T:G	K930Q	0.998
19:10354167:G:T	A928E	0.998
19:10354224:C:T	G909D	0.998

dbSNP variants (sampled 300 via entrez): RS1000073660 (19:10380138 G>A), RS1000073948 (19:10378781 G>A), RS1000124266 (19:10369447 CT>C), RS1000149134 (19:10372470 ATATATATATATATATTTTTTTTTTTT>A), RS1000153572 (19:10377174 G>C), RS1000243715 (19:10371312 A>G), RS1000294663 (19:10371005 G>C), RS1000402289 (19:10381249 A>G), RS1000484992 (19:10361194 G>A,T), RS1000522719 (19:10373522 G>C), RS1000539763 (19:10378808 C>G), RS1000559883 (19:10372625 G>T), RS1000576244 (19:10373250 C>G), RS1000632192 (19:10372945 C>T), RS1001007494 (19:10356104 C>A,G,T)

Disease associations

OMIM: gene MIM:176941 | disease phenotypes: MIM:611521, MIM:300755

GenCC curated gene-disease

Disease	Classification	Inheritance
immunodeficiency 35	Strong	Autosomal recessive

Mondo (2): immunodeficiency 35 (MONDO:0012682), immunodeficiency disease (MONDO:0021094)

Orphanet (1): Susceptibility to infection due to TYK2 deficiency (Orphanet:331226)

HPO phenotypes

7 total (7 of 7 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0002205	Recurrent respiratory infections
HP:0002721	Immunodeficiency
HP:0002841	Recurrent fungal infections
HP:0003212	Increased circulating IgE concentration
HP:0004429	Recurrent viral infections
HP:0011274	Recurrent mycobacterial infections

GWAS associations

56 associations (top):

Study	Trait	p-value
GCST000539_1	Type 1 diabetes	4.000000e-09
GCST000833_10	Psoriasis	4.000000e-09
GCST000833_6	Psoriasis	4.000000e-11
GCST000879_7	Crohn’s disease	1.000000e-12
GCST001191_14	Type 1 diabetes	1.000000e-10
GCST001198_11	Multiple sclerosis	1.000000e-06
GCST001725_60	Inflammatory bowel disease	2.000000e-18
GCST002318_164	Rheumatoid arthritis	5.000000e-16
GCST003097_31	Pediatric autoimmune diseases	4.000000e-07
GCST003129_12	Primary biliary cholangitis	1.000000e-10
GCST003155_24	Systemic lupus erythematosus	4.000000e-13
GCST003156_29	Systemic lupus erythematosus	1.000000e-13
GCST003268_26	Psoriasis vulgaris	1.000000e-16
GCST003270_13	Psoriatic arthritis	2.000000e-06
GCST003620_8	Systemic lupus erythematosus or rheumatoid arthritis	3.000000e-08
GCST003622_55	Systemic lupus erythematosus	2.000000e-12
GCST004131_88	Inflammatory bowel disease	2.000000e-11
GCST004132_111	Crohn’s disease	3.000000e-13
GCST004603_190	Platelet count	7.000000e-13
GCST004627_184	Lymphocyte count	2.000000e-25
GCST004633_9	Neutrophil percentage of white cells	4.000000e-10
GCST005527_19	Psoriasis	9.000000e-31
GCST005527_41	Psoriasis	3.000000e-10
GCST005528_13	Juvenile idiopathic arthritis (oligoarticular or rheumatoid factor-negative polyarticular)	1.000000e-10
GCST005529_5	Ankylosing spondylitis	3.000000e-10
GCST005529_62	Ankylosing spondylitis	7.000000e-09
GCST005531_66	Multiple sclerosis	2.000000e-14
GCST005536_18	Type 1 diabetes	4.000000e-15
GCST005536_44	Type 1 diabetes	4.000000e-07
GCST005537_46	Chronic inflammatory diseases (ankylosing spondylitis, Crohn’s disease, psoriasis, primary sclerosing cholangitis, ulcerative colitis) (pleiotropy)	5.000000e-12

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:1001494	psoriasis vulgaris
EFO:0004309	platelet count
EFO:0004587	lymphocyte count
EFO:0007990	neutrophil percentage of leukocytes
EFO:0009933	Thyroid preparation use measurement
EFO:0004346	neuroimaging measurement
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0007985	platelet crit

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C566928	Tyrosine Kinase 2 Deficiency (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (6): CHEMBL2363062 (PROTEIN FAMILY), CHEMBL3301390 (PROTEIN COMPLEX), CHEMBL3301391 (PROTEIN COMPLEX), CHEMBL3301392 (PROTEIN COMPLEX), CHEMBL3553 (SINGLE PROTEIN), CHEMBL6066058 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

72 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 107,628 (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
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL1789941	RUXOLITINIB	4	11,547
CHEMBL221959	TOFACITINIB	4	10,408
CHEMBL3622821	UPADACITINIB	4	2,726
CHEMBL2105759	BARICITINIB	4	6,741
CHEMBL3301607	FILGOTINIB	4	2,905
CHEMBL3655081	ABROCITINIB	4	1,037
CHEMBL4435170	DEUCRAVACITINIB	4	679
CHEMBL1078178	MOMELOTINIB	4	3,481
CHEMBL1289926	AXITINIB	4	15,732
CHEMBL1795071	RUXOLITINIB PHOSPHATE	4	3,220
CHEMBL1834657	INFIGRATINIB PHOSPHATE	4	285
CHEMBL1852688	INFIGRATINIB	4	2,209
CHEMBL2035187	PACRITINIB	4	3,345
CHEMBL2103743	TOFACITINIB CITRATE	4	1,672
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL3137308	PEFICITINIB	4	1,722
CHEMBL4596392	CRAVACITINIB	4	25
CHEMBL477772	PAZOPANIB	4	15,540
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL535	SUNITINIB	4
CHEMBL5416410	DASATINIB	4
CHEMBL553	ERLOTINIB	4
CHEMBL601719	CRIZOTINIB	4
CHEMBL608533	MIDOSTAURIN	4
CHEMBL941	IMATINIB	4
CHEMBL4297507	DELGOCITINIB	3
CHEMBL3137331	DEFACTINIB	3
CHEMBL3622820	ITACITINIB	3
CHEMBL428690	ALVOCIDIB	3

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Janus kinase (JakA) family

Most potent curated ligand interactions (51 total), top 25:

Ligand	Action	Affinity	Parameter
deucravacitinib	Inhibition	10.7	pKi
BMS-986202	Inhibition	10.7	pKi
izencitinib	Inhibition	10.0	pKi
soficitinib	Inhibition	9.3	pIC50
cerdulatinib	Inhibition	9.3	pIC50
SJ988497	Binding	9.27	pKd
vexicitinib	Inhibition	9.09	pIC50
JAK inhibitor I	Inhibition	9.0	pIC50
SDC-1801	Inhibition	8.72	pIC50
cadefrecitinib	Inhibition	8.64	pIC50
nezulcitinib	Inhibition	8.6	pKi
nomelcitinib	Inhibition	8.6	pIC50
GDC-0214	Inhibition	8.5	pKi
compound 29 [Moslin et al., 2017]	Inhibition	8.4	pIC50
peficitinib	Inhibition	8.3	pIC50
lorpucitinib	Inhibition	8.13	pIC50
TYK2 inhibitor 14l	Inhibition	8.05	pIC50
SAR-20347	Inhibition	7.89	pIC50
zotiraciclib	Inhibition	7.85	pIC50
ropsacitinib	Inhibition	7.82	pIC50
momelotinib	Inhibition	7.7	pIC50
ilginatinib	Inhibition	7.66	pIC50
brepocitinib	Inhibition	7.64	pIC50
PF-06263276	Inhibition	7.53	pIC50
TYK2 inhibitor 18 [WO2023227946]	Inhibition	7.52	pIC50

Binding affinities (BindingDB)

2229 measured of 2855 human assays (2857 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
US20260001898, Example A1	KD	0.004 nM	US-20260001898: Heteroaryl compounds as inhibitors of TYK2/JAK1, composition and application thereof
[2-[6-(2-ethyl-5-fluoro-4-hydroxyphenyl)-2,3,3a,4,5,6,7,7a-octahydro-1H-indazol-3-yl]-4,5,6,7-tetrahydro-3H-imidazo[4,5-c]pyridin-6-yl]-(4-propan-2-ylpiperazin-1-yl)methanone	KI	0.08 nM	US-10208040: Fused imidazo-piperidine JAK inhibitors
US9216999, 435b	IC50	0.11 nM	US-9216999: Substituted pyrrolo[2,3-h][1,6]naphthyridines and compositions thereof as JAK inhibitors
4-[3-(5-fluoropyrimidin-2-yl)-2-methoxyanilino]-2-[(3R)-3-(methylcarbamoyl)pyrrolidin-1-yl]pyrimidine-5-carboxamide	KD	0.11 nM	US-20250257051: SUBSTITUTED PYRIMIDINE COMPOUNDS AS TYK2 INHIBITORS
US9216999, 427	IC50	0.16 nM	US-9216999: Substituted pyrrolo[2,3-h][1,6]naphthyridines and compositions thereof as JAK inhibitors
US9216999, 75	IC50	0.2 nM	US-9216999: Substituted pyrrolo[2,3-h][1,6]naphthyridines and compositions thereof as JAK inhibitors
2-[4-[4-[(2R)-2-hydroxypropyl]-3,5,8,10-tetrazatricyclo[7.3.0.02,6]dodeca-1,4,6,8,11-pentaen-3-yl]cyclohexyl]acetonitrile	IC50	0.2 nM	US-10294226: Small molecule inhibitors of the JAK family of kinases
((S)-2-(6-(2-ethyl-5-fluoro-4-hydroxyphenyl)-1H-indazol-3-yl)-5-propyl-4,5,6,7-tetrahydro-3H-imidazo[4,5-c]pyridin-6-yl)((1S,4S)-5-methyl-2,5-diazabicyclo-[2.2.1]heptan-2-yl)methanone	KI	0.25 nM	US-10208040: Fused imidazo-piperidine JAK inhibitors
[(6S)-2-[6-(2-ethyl-5-fluoro-4-hydroxyphenyl)-2,3,3a,4,5,6,7,7a-octahydro-1H-indazol-3-yl]-5-methyl-3,4,6,7-tetrahydroimidazo[4,5-c]pyridin-6-yl]-(4-propan-2-ylpiperazin-1-yl)methanone	KI	0.25 nM	US-10208040: Fused imidazo-piperidine JAK inhibitors
[2-[[2-(2,6-dichlorophenyl)-[1,3]thiazolo[5,4-c]pyridin-4-yl]amino]-4-pyridinyl]methanol	KI	0.3 nM	US-8697708: Azabenzothiazole compounds, compositions and methods of use
4-[(6-aminopyrimidin-4-yl)amino]-2-(2-fluoro-6-isocyanophenyl)-[1,3]thiazolo[5,4-c]pyridine-7-carbonitrile	KI	0.3 nM	US-8697708: Azabenzothiazole compounds, compositions and methods of use
6-[[4-(methoxymethyl)-2-pyridinyl]amino]-4-[2-methoxy-3-(2-methyltetrazol-5-yl)anilino]-2-methyl-3a,4,5,6,7,7a-hexahydro-1H-pyrazolo[3,4-b]pyridin-3-one	KD	0.3 nM	US-10323036: TYK2 inhibitors and uses thereof
4-[2-methoxy-3-(2-methyltetrazol-5-yl)anilino]-2-methyl-6-[(5-methyl-2-pyridinyl)amino]-3a,4,5,6,7,7a-hexahydro-1H-pyrazolo[3,4-b]pyridin-3-one	KD	0.3 nM	US-10323036: TYK2 inhibitors and uses thereof
4-[2-methoxy-3-(2-methyltetrazol-5-yl)anilino]-2-methyl-6-(pyridin-2-ylamino)-3a,4,5,6,7,7a-hexahydro-1H-pyrazolo[3,4-b]pyridin-3-one	KD	0.3 nM	US-10323036: TYK2 inhibitors and uses thereof
N-[4-[2-methoxy-3-(1-methyl-1,2,4-triazol-3-yl)anilino]-2-methyl-3-oxo-3a,4,5,6,7,7a-hexahydro-1H-pyrazolo[3,4-b]pyridin-6-yl]cyclopropanecarboxamide	KD	0.3 nM	US-10323036: TYK2 inhibitors and uses thereof
6-[[4-(methoxymethyl)-2-pyridinyl]amino]-4-[2-methoxy-3-(1-methyl-1,2,4-triazol-3-yl)anilino]-2-methyl-3a,4,5,6,7,7a-hexahydro-1H-pyrazolo[3,4-b]pyridin-3-one	KD	0.3 nM	US-10323036: TYK2 inhibitors and uses thereof
4-[2-methoxy-3-(1-methyl-1,2,4-triazol-3-yl)anilino]-2-methyl-6-[(5-methyl-2-pyridinyl)amino]-3a,4,5,6,7,7a-hexahydro-1H-pyrazolo[3,4-b]pyridin-3-one	KD	0.3 nM	US-10323036: TYK2 inhibitors and uses thereof
4-[2-methoxy-3-(1-methyl-1,2,4-triazol-3-yl)anilino]-2-methyl-6-[(4-methyl-2-pyridinyl)amino]-3a,4,5,6,7,7a-hexahydro-1H-pyrazolo[3,4-b]pyridin-3-one	KD	0.3 nM	US-10323036: TYK2 inhibitors and uses thereof
4-[2-methoxy-3-(1-methyl-1,2,4-triazol-3-yl)anilino]-2-methyl-6-[(5-morpholin-4-yl-2-pyridinyl)amino]-3a,4,5,6,7,7a-hexahydro-1H-pyrazolo[3,4-b]pyridin-3-one	KD	0.3 nM	US-10323036: TYK2 inhibitors and uses thereof
6-[(5-fluoro-4-methyl-2-pyridinyl)amino]-4-[2-methoxy-3-(1-methyl-1,2,4-triazol-3-yl)anilino]-2-methyl-3a,4,5,6,7,7a-hexahydro-1H-pyrazolo[3,4-b]pyridin-3-one	KD	0.3 nM	US-10323036: TYK2 inhibitors and uses thereof
4-[2-methoxy-3-(1-methyl-1,2,4-triazol-3-yl)anilino]-2-methyl-6-[(5-piperidin-1-yl-2-pyridinyl)amino]-3a,4,5,6,7,7a-hexahydro-1H-pyrazolo[3,4-b]pyridin-3-one	KD	0.3 nM	US-10323036: TYK2 inhibitors and uses thereof
6-[[4-[2-methoxy-3-(1-methyl-1,2,4-triazol-3-yl)anilino]-2-methyl-3-oxo-3a,4,5,6,7,7a-hexahydro-1H-pyrazolo[3,4-b]pyridin-6-yl]amino]pyridine-3-carbonitrile	KD	0.3 nM	US-10323036: TYK2 inhibitors and uses thereof
6-[[4-[2-methoxy-3-(2-methyltetrazol-5-yl)anilino]-2-methyl-3-oxo-3a,4,5,6,7,7a-hexahydro-1H-pyrazolo[3,4-b]pyridin-6-yl]amino]pyrimidine-4-carbonitrile	KD	0.3 nM	US-10323036: TYK2 inhibitors and uses thereof
N-[4-[3-(1,5-dimethyl-1,2,4-triazol-3-yl)-2-methoxyanilino]-2-methyl-3-oxo-3a,4,5,6,7,7a-hexahydro-1H-pyrazolo[3,4-b]pyridin-6-yl]cyclopropanecarboxamide	KD	0.3 nM	US-10323036: TYK2 inhibitors and uses thereof
6-[(5-cyclopropyl-2-pyridinyl)amino]-4-[2-methoxy-3-(2-methyltetrazol-5-yl)anilino]-2-methyl-3a,4,5,6,7,7a-hexahydro-1H-pyrazolo[3,4-b]pyridin-3-one	KD	0.3 nM	US-10323036: TYK2 inhibitors and uses thereof
4-[2-methoxy-3-(2-methyltetrazol-5-yl)anilino]-2-methyl-6-[[6-(trifluoromethyl)-2-pyridinyl]amino]-3a,4,5,6,7,7a-hexahydro-1H-pyrazolo[3,4-b]pyridin-3-one	KD	0.3 nM	US-10323036: TYK2 inhibitors and uses thereof
6-[[6-(3-methoxyazetidin-1-yl)-2-pyridinyl]amino]-4-[2-methoxy-3-(2-methyltetrazol-5-yl)anilino]-2-methyl-3a,4,5,6,7,7a-hexahydro-1H-pyrazolo[3,4-b]pyridin-3-one	KD	0.3 nM	US-10323036: TYK2 inhibitors and uses thereof
6-[(6-cyclopropyl-2-pyridinyl)amino]-4-[2-methoxy-3-(2-methyltetrazol-5-yl)anilino]-2-methyl-3a,4,5,6,7,7a-hexahydro-1H-pyrazolo[3,4-b]pyridin-3-one	KD	0.3 nM	US-10323036: TYK2 inhibitors and uses thereof
6-[[4-[2-methoxy-4-(methoxymethyl)anilino]-2-methyl-3-oxo-3a,4,5,6,7,7a-hexahydro-1H-pyrazolo[3,4-b]pyridin-6-yl]amino]pyridine-2-carbonitrile	KD	0.3 nM	US-10323036: TYK2 inhibitors and uses thereof
N-[4-[2-methoxy-4-(pyrrolidine-1-carbonyl)anilino]-2-methyl-3-oxo-3a,4,5,6,7,7a-hexahydro-1H-pyrazolo[3,4-b]pyridin-6-yl]cyclopropanecarboxamide	KD	0.3 nM	US-10323036: TYK2 inhibitors and uses thereof
6-[(2,6-dimethylpyrimidin-4-yl)amino]-4-(3-fluoro-2-methoxyanilino)-2-methyl-3a,4,5,6,7,7a-hexahydro-1H-pyrazolo[3,4-b]pyridin-3-one	KD	0.3 nM	US-10323036: TYK2 inhibitors and uses thereof
4-(3-fluoro-2-methoxyanilino)-2-methyl-6-[(6-methylpyridazin-3-yl)amino]-3a,4,5,6,7,7a-hexahydro-1H-pyrazolo[3,4-b]pyridin-3-one	KD	0.3 nM	US-10323036: TYK2 inhibitors and uses thereof
6-[[4-(3-fluoro-2-methoxyanilino)-2-methyl-3-oxo-3a,4,5,6,7,7a-hexahydro-1H-pyrazolo[3,4-b]pyridin-6-yl]amino]pyridine-2-carbonitrile	KD	0.3 nM	US-10323036: TYK2 inhibitors and uses thereof
N-[4-[4-(azetidine-1-carbonyl)-2-methoxyanilino]-2-methyl-3-oxo-3a,4,5,6,7,7a-hexahydro-1H-pyrazolo[3,4-b]pyridin-6-yl]cyclopropanecarboxamide	KD	0.3 nM	US-10323036: TYK2 inhibitors and uses thereof
4-[2-methoxy-4-(methoxymethyl)anilino]-2-methyl-6-[[5-(pyrrolidine-1-carbonyl)-6-(trifluoromethyl)-2-pyridinyl]amino]-3a,4,5,6,7,7a-hexahydro-1H-pyrazolo[3,4-b]pyridin-3-one	KD	0.3 nM	US-10323036: TYK2 inhibitors and uses thereof
4-(3-chloro-2-methoxyanilino)-6-[(2,6-dimethylpyrimidin-4-yl)amino]-2-methyl-3a,4,5,6,7,7a-hexahydro-1H-pyrazolo[3,4-b]pyridin-3-one	KD	0.3 nM	US-10323036: TYK2 inhibitors and uses thereof
6-[(5-fluoro-4-methyl-2-pyridinyl)amino]-2-methyl-4-(2-methylsulfonylanilino)-3a,4,5,6,7,7a-hexahydro-1H-pyrazolo[3,4-b]pyridin-3-one	KD	0.3 nM	US-10323036: TYK2 inhibitors and uses thereof
6-[(2,6-dimethylpyrimidin-4-yl)amino]-2-methyl-4-(2-methylsulfonylanilino)-3a,4,5,6,7,7a-hexahydro-1H-pyrazolo[3,4-b]pyridin-3-one	KD	0.3 nM	US-10323036: TYK2 inhibitors and uses thereof
2-methyl-6-[(6-methylpyridazin-3-yl)amino]-4-(2-methylsulfonylanilino)-3a,4,5,6,7,7a-hexahydro-1H-pyrazolo[3,4-b]pyridin-3-one	KD	0.3 nM	US-10323036: TYK2 inhibitors and uses thereof
2-methyl-6-[(5-methyl-2-pyridinyl)amino]-4-(2-methylsulfonylanilino)-3a,4,5,6,7,7a-hexahydro-1H-pyrazolo[3,4-b]pyridin-3-one	KD	0.3 nM	US-10323036: TYK2 inhibitors and uses thereof
2-methyl-4-(2-methylsulfonylanilino)-6-[[6-(trifluoromethyl)-2-pyridinyl]amino]-3a,4,5,6,7,7a-hexahydro-1H-pyrazolo[3,4-b]pyridin-3-one	KD	0.3 nM	US-10323036: TYK2 inhibitors and uses thereof
6-[[4-[2-methoxy-3-(1-methylpyrazol-3-yl)anilino]-2-methyl-3-oxo-3a,4,5,6,7,7a-hexahydro-1H-pyrazolo[3,4-b]pyridin-6-yl]amino]pyridine-2-carbonitrile	KD	0.3 nM	US-10323036: TYK2 inhibitors and uses thereof
6-[(2,6-dimethylpyrimidin-4-yl)amino]-4-[2-methoxy-3-(1-methylpyrazol-3-yl)anilino]-2-methyl-3a,4,5,6,7,7a-hexahydro-1H-pyrazolo[3,4-b]pyridin-3-one	KD	0.3 nM	US-10323036: TYK2 inhibitors and uses thereof
4-(3-chloro-2-methoxyanilino)-2-methyl-6-[[5-(pyrrolidine-1-carbonyl)-6-(trifluoromethyl)-2-pyridinyl]amino]-3a,4,5,6,7,7a-hexahydro-1H-pyrazolo[3,4-b]pyridin-3-one	KD	0.3 nM	US-10323036: TYK2 inhibitors and uses thereof
N-[2-methyl-4-[2-[methyl(methylsulfonyl)amino]anilino]-3-oxo-3a,4,5,6,7,7a-hexahydro-1H-pyrazolo[3,4-b]pyridin-6-yl]cyclopropanecarboxamide	KD	0.3 nM	US-10323036: TYK2 inhibitors and uses thereof
4-(3-chloro-2-methoxyanilino)-2-methyl-6-[[5-(morpholine-4-carbonyl)-6-(trifluoromethyl)-2-pyridinyl]amino]-3a,4,5,6,7,7a-hexahydro-1H-pyrazolo[3,4-b]pyridin-3-one	KD	0.3 nM	US-10323036: TYK2 inhibitors and uses thereof
N-[4-[2-methoxy-3-(5-methyl-1,2,4-oxadiazol-3-yl)anilino]-2-methyl-3-oxo-3a,4,5,6,7,7a-hexahydro-1H-pyrazolo[3,4-b]pyridin-6-yl]cyclopropanecarboxamide	KD	0.3 nM	US-10323036: TYK2 inhibitors and uses thereof
6-[[4-(3-chloro-2-methoxyanilino)-2-methyl-3-oxo-3a,4,5,6,7,7a-hexahydro-1H-pyrazolo[3,4-b]pyridin-6-yl]amino]-3-methylpyridine-2-carbonitrile	KD	0.3 nM	US-10323036: TYK2 inhibitors and uses thereof
6-[(5-fluoro-4-methyl-2-pyridinyl)amino]-4-[3-(1H-imidazol-5-yl)-2-methoxyanilino]-2-methyl-3a,4,5,6,7,7a-hexahydro-1H-pyrazolo[3,4-b]pyridin-3-one	KD	0.3 nM	US-10323036: TYK2 inhibitors and uses thereof
6-[[4-(3-chloro-2-methoxyanilino)-2-methyl-3-oxo-3a,4,5,6,7,7a-hexahydro-1H-pyrazolo[3,4-b]pyridin-6-yl]amino]-3-(2-oxopyrrolidin-1-yl)pyridine-2-carbonitrile	KD	0.3 nM	US-10323036: TYK2 inhibitors and uses thereof

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
11.00	IC50	0.01	nM	CHEMBL5427107
10.82	Ki	0.015	nM	CHEMBL4460368
10.80	IC50	0.016	nM	CHEMBL5427277
10.74	Ki	0.018	nM	CHEMBL4442827
10.74	IC50	0.018	nM	CHEMBL5422022
10.72	Kd	0.019	nM	CHEMBL5433700
10.72	Kd	0.019	nM	CHEMBL5424497
10.70	Ki	0.02	nM	DEUCRAVACITINIB
10.70	Ki	0.02	nM	BMS-986202
10.66	Kd	0.022	nM	CHEMBL5424894
10.64	Kd	0.023	nM	CHEMBL5398548
10.64	Kd	0.023	nM	CHEMBL5424894
10.62	Ki	0.024	nM	CHEMBL4571920
10.59	IC50	0.026	nM	CHEMBL5416227
10.59	IC50	0.026	nM	CHEMBL5418288
10.57	IC50	0.027	nM	CHEMBL5420349
10.55	Kd	0.028	nM	CHEMBL5419627
10.48	Kd	0.033	nM	CHEMBL5407138
10.47	Kd	0.034	nM	CHEMBL5430689
10.46	Ki	0.035	nM	CHEMBL4439957
10.42	IC50	0.038	nM	CHEMBL5417355
10.41	Kd	0.039	nM	CHEMBL5415951
10.30	IC50	0.05	nM	CHEMBL5437122
10.30	IC50	0.05	nM	CHEMBL5440225
10.30	Ki	0.05	nM	CHEMBL6048102
10.30	Ki	0.05	nM	CHEMBL5879865
10.30	Ki	0.05	nM	CHEMBL6028729
10.30	Ki	0.05	nM	CHEMBL5994009
10.30	Ki	0.05	nM	CHEMBL5981476
10.30	Ki	0.05	nM	CHEMBL5819557
10.30	Ki	0.05	nM	CHEMBL5807669
10.30	Ki	0.05	nM	CHEMBL5985265
10.30	Ki	0.05	nM	CHEMBL5840367
10.30	Ki	0.05	nM	CHEMBL5805686
10.30	Ki	0.05	nM	CHEMBL5785787
10.30	Ki	0.05	nM	CHEMBL5935458
10.30	Ki	0.05	nM	CHEMBL5816231
10.30	Ki	0.05	nM	CHEMBL5943374
10.30	Ki	0.05	nM	CHEMBL5923101
10.30	Ki	0.05	nM	CHEMBL5995806
10.30	Ki	0.05	nM	CHEMBL5879376
10.30	Ki	0.05	nM	CHEMBL5931775
10.30	Ki	0.05	nM	CHEMBL5817496
10.30	Ki	0.05	nM	CHEMBL6021065
10.30	Ki	0.05	nM	CHEMBL5794881
10.30	Ki	0.05	nM	CHEMBL5976818
10.29	Ki	0.051	nM	CHEMBL5200655
10.28	IC50	0.053	nM	CHEMBL5418288
10.22	Ki	0.06	nM	CHEMBL4561663
10.22	IC50	0.06	nM	CHEMBL5412034

PubChem BioAssay actives

2381 with measured affinity, of 4624 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
6-[[1-(1,5-dimethylpyrazol-3-yl)-2-oxo-3-pyridinyl]amino]-N-[(1R,2S)-2-fluorocyclopropyl]-8-(methylamino)imidazo[1,2-b]pyridazine-3-carboxamide	1603362: Inhibition of fluorescein-labeled kinase tracer binding to His-TVMV-fused TYK2 JH2 domain (575 to 869 residues) (unknown origin) measured after 90 mins by HTRF assay	ki	<0.0001	uM
N-[(1R,2S)-2-fluorocyclopropyl]-8-(methylamino)-6-[[1-(6-methylpyridazin-3-yl)-2-oxo-3-pyridinyl]amino]imidazo[1,2-b]pyridazine-3-carboxamide	1603362: Inhibition of fluorescein-labeled kinase tracer binding to His-TVMV-fused TYK2 JH2 domain (575 to 869 residues) (unknown origin) measured after 90 mins by HTRF assay	ki	<0.0001	uM
Deucravacitinib	1534892: Inhibition of TYK2 in human Jurkat cells assessed as reduction in IFN-alpha stimulated TYK2 phosphorylation by caspase3/7 reagent-based Western blot analysis	ki	<0.0001	uM
N-[(1S,2S)-2-methoxycyclobutyl]-7-(methylamino)-5-[[1-[(3R)-oxan-3-yl]-2-oxo-3-pyridinyl]amino]pyrazolo[1,5-a]pyrimidine-3-carboxamide	1975430: Binding affinity to human wild type TYK2 JH2 domain (G556/D888) expressed in mammalian expression system	kd	<0.0001	uM
N-[(1R,2R)-2-methoxycyclobutyl]-7-(methylamino)-5-[(2-oxo-1-pyridin-2-yl-3-pyridinyl)amino]pyrazolo[1,5-a]pyrimidine-3-carboxamide	2011264: Binding affinity to TYK2 JH2 (unknown origin) assessed as dissociation constant	kd	<0.0001	uM
N-[(1S,2S)-2-methoxycyclobutyl]-7-(methylamino)-5-[(2-oxo-1-pyridin-2-yl-3-pyridinyl)amino]pyrazolo[1,5-a]pyrimidine-3-carboxamide	1975430: Binding affinity to human wild type TYK2 JH2 domain (G556/D888) expressed in mammalian expression system	kd	<0.0001	uM
N-[(1S,2S)-2-methoxycyclobutyl]-7-(methylamino)-5-[[1-(6-methyl-3-pyridinyl)-2-oxo-3-pyridinyl]amino]pyrazolo[1,5-a]pyrimidine-3-carboxamide	1975430: Binding affinity to human wild type TYK2 JH2 domain (G556/D888) expressed in mammalian expression system	kd	<0.0001	uM
5-[[1-(3-fluoro-2-pyridinyl)-2-oxo-3-pyridinyl]amino]-N-[(1R,2R)-2-methoxycyclobutyl]-7-(methylamino)pyrazolo[1,5-a]pyrimidine-3-carboxamide	1975430: Binding affinity to human wild type TYK2 JH2 domain (G556/D888) expressed in mammalian expression system	kd	<0.0001	uM
5-[[1-(3-fluoro-2-pyridinyl)-2-oxo-3-pyridinyl]amino]-N-[(1S,2S)-2-hydroxycyclobutyl]-7-(methylamino)pyrazolo[1,5-a]pyrimidine-3-carboxamide	1975430: Binding affinity to human wild type TYK2 JH2 domain (G556/D888) expressed in mammalian expression system	kd	<0.0001	uM
5-[[1-(5-fluoro-3-pyridinyl)-2-oxo-3-pyridinyl]amino]-N-[(1S,2S)-2-methoxycyclobutyl]-7-(methylamino)pyrazolo[1,5-a]pyrimidine-3-carboxamide	1975430: Binding affinity to human wild type TYK2 JH2 domain (G556/D888) expressed in mammalian expression system	kd	<0.0001	uM
N-[(1S,2S)-2-methoxycyclobutyl]-7-(methylamino)-5-[[1-(oxan-4-yl)-2-oxo-3-pyridinyl]amino]pyrazolo[1,5-a]pyrimidine-3-carboxamide	1975430: Binding affinity to human wild type TYK2 JH2 domain (G556/D888) expressed in mammalian expression system	kd	<0.0001	uM
5-[[1-(3-fluoro-2-pyridinyl)-2-oxo-3-pyridinyl]amino]-N-[[1-(hydroxymethyl)cyclopropyl]methyl]-7-(methylamino)pyrazolo[1,5-a]pyrimidine-3-carboxamide	1975430: Binding affinity to human wild type TYK2 JH2 domain (G556/D888) expressed in mammalian expression system	kd	<0.0001	uM
N-cyclopropyl-5-[(2-methoxy-3-pyridinyl)amino]-7-(methylamino)pyrazolo[1,5-a]pyrimidine-3-carboxamide	1975430: Binding affinity to human wild type TYK2 JH2 domain (G556/D888) expressed in mammalian expression system	kd	<0.0001	uM
N-[(1S,2S)-2-methoxycyclobutyl]-7-(methylamino)-5-[(2-oxo-1-pyridin-3-yl-3-pyridinyl)amino]pyrazolo[1,5-a]pyrimidine-3-carboxamide	1975430: Binding affinity to human wild type TYK2 JH2 domain (G556/D888) expressed in mammalian expression system	kd	<0.0001	uM
N-[(1S,2S)-2-methoxycyclobutyl]-7-(methylamino)-5-[(2-oxo-1-propan-2-yl-3-pyridinyl)amino]pyrazolo[1,5-a]pyrimidine-3-carboxamide	1975430: Binding affinity to human wild type TYK2 JH2 domain (G556/D888) expressed in mammalian expression system	kd	<0.0001	uM
5-[[1-(3-fluoro-2-pyridinyl)-2-oxo-3-pyridinyl]amino]-N-[(1R,2S)-2-hydroxycyclobutyl]-7-(methylamino)pyrazolo[1,5-a]pyrimidine-3-carboxamide	1975430: Binding affinity to human wild type TYK2 JH2 domain (G556/D888) expressed in mammalian expression system	kd	<0.0001	uM
5-[[1-[1-(2-fluoroethyl)piperidin-4-yl]-2-oxo-3-pyridinyl]amino]-N-[(1S,2S)-2-methoxycyclobutyl]-7-(methylamino)pyrazolo[1,5-a]pyrimidine-3-carboxamide	1975430: Binding affinity to human wild type TYK2 JH2 domain (G556/D888) expressed in mammalian expression system	kd	<0.0001	uM
N-[(1S,2S)-2-methoxycyclobutyl]-7-(methylamino)-5-[[1-(4-methyl-1,3-oxazol-2-yl)-2-oxo-3-pyridinyl]amino]pyrazolo[1,5-a]pyrimidine-3-carboxamide	1975430: Binding affinity to human wild type TYK2 JH2 domain (G556/D888) expressed in mammalian expression system	kd	<0.0001	uM
N-[(1S,2S)-2-methoxycyclobutyl]-7-(methylamino)-5-[[1-(1,3-oxazol-2-yl)-2-oxo-3-pyridinyl]amino]pyrazolo[1,5-a]pyrimidine-3-carboxamide	1975430: Binding affinity to human wild type TYK2 JH2 domain (G556/D888) expressed in mammalian expression system	kd	<0.0001	uM
N-[(1S,2S)-2-methoxycyclobutyl]-7-(methylamino)-5-[[1-[(3S)-oxan-3-yl]-2-oxo-3-pyridinyl]amino]pyrazolo[1,5-a]pyrimidine-3-carboxamide	1975430: Binding affinity to human wild type TYK2 JH2 domain (G556/D888) expressed in mammalian expression system	kd	<0.0001	uM
5-[[1-(3-fluoro-2-pyridinyl)-2-oxo-3-pyridinyl]amino]-N-[(1S,2S)-2-methoxycyclopropyl]-7-(methylamino)pyrazolo[1,5-a]pyrimidine-3-carboxamide	1975430: Binding affinity to human wild type TYK2 JH2 domain (G556/D888) expressed in mammalian expression system	kd	<0.0001	uM
N-[(1R,2R)-2-methoxycyclobutyl]-5-[[1-(4-methoxycyclohexyl)-2-oxo-3-pyridinyl]amino]-7-(methylamino)pyrazolo[1,5-a]pyrimidine-3-carboxamide	1975430: Binding affinity to human wild type TYK2 JH2 domain (G556/D888) expressed in mammalian expression system	kd	<0.0001	uM
N-[(1R,2R)-2-methoxycyclobutyl]-7-(methylamino)-5-[[1-(2-methyl-1,3-oxazol-5-yl)-2-oxo-3-pyridinyl]amino]pyrazolo[1,5-a]pyrimidine-3-carboxamide	1975430: Binding affinity to human wild type TYK2 JH2 domain (G556/D888) expressed in mammalian expression system	kd	<0.0001	uM
5-[[1-(5-fluoro-2-pyridinyl)-2-oxo-3-pyridinyl]amino]-N-[(1R,2R)-2-methoxycyclobutyl]-7-(methylamino)pyrazolo[1,5-a]pyrimidine-3-carboxamide	1975430: Binding affinity to human wild type TYK2 JH2 domain (G556/D888) expressed in mammalian expression system	kd	<0.0001	uM
N-[(1R,2R)-2-methoxycyclobutyl]-7-(methylamino)-5-[[1-(4-methyl-1,3-oxazol-5-yl)-2-oxo-3-pyridinyl]amino]pyrazolo[1,5-a]pyrimidine-3-carboxamide	1975430: Binding affinity to human wild type TYK2 JH2 domain (G556/D888) expressed in mammalian expression system	kd	<0.0001	uM
N-[(1S,2S)-2-methoxycyclobutyl]-7-(methylamino)-5-[[1-(oxetan-3-yl)-2-oxo-3-pyridinyl]amino]pyrazolo[1,5-a]pyrimidine-3-carboxamide	1975430: Binding affinity to human wild type TYK2 JH2 domain (G556/D888) expressed in mammalian expression system	kd	<0.0001	uM
N-[(1S,2S)-2-methoxycyclobutyl]-5-[[1-(3-methoxycyclobutyl)-2-oxo-3-pyridinyl]amino]-7-(methylamino)pyrazolo[1,5-a]pyrimidine-3-carboxamide	1975430: Binding affinity to human wild type TYK2 JH2 domain (G556/D888) expressed in mammalian expression system	kd	<0.0001	uM
N-[(1S)-2,2-difluorocyclobutyl]-5-[[1-(3-fluoro-2-pyridinyl)-2-oxo-3-pyridinyl]amino]-7-(methylamino)pyrazolo[1,5-a]pyrimidine-3-carboxamide	1975430: Binding affinity to human wild type TYK2 JH2 domain (G556/D888) expressed in mammalian expression system	kd	<0.0001	uM
5-[[1-(3-fluoro-2-pyridinyl)-2-oxo-3-pyridinyl]amino]-7-(methylamino)-N-[(1R,2R)-2-(trideuteriomethoxy)cyclobutyl]pyrazolo[1,5-a]pyrimidine-3-carboxamide	1975430: Binding affinity to human wild type TYK2 JH2 domain (G556/D888) expressed in mammalian expression system	kd	<0.0001	uM
6-(azetidine-1-carbonylamino)-4-[2-methoxy-3-(1-methyl-1,2,4-triazol-3-yl)anilino]-N-methylpyridazine-3-carboxamide	2029526: Binding affinity to human wild-type partial length TYK2 JH2 (G556 to D888 residues) expressed in mammalian expression system by KINOMEscan assay	kd	<0.0001	uM
(11R)-4-methoxy-11-methyl-18-(methylamino)-9-oxa-2,12,16,20,21-pentazatetracyclo[12.5.2.13,7.017,21]docosa-1(20),3,5,7(22),14,16,18-heptaen-13-one	2029546: Binding affinity to TYK2 JH2 (unknown origin)	kd	<0.0001	uM
N-[(1R,2S)-2-fluorocyclopropyl]-6-[[1-(5-fluoro-2-pyridinyl)-2-oxo-3-pyridinyl]amino]-8-(methylamino)imidazo[1,2-b]pyridazine-3-carboxamide	1603362: Inhibition of fluorescein-labeled kinase tracer binding to His-TVMV-fused TYK2 JH2 domain (575 to 869 residues) (unknown origin) measured after 90 mins by HTRF assay	ki	<0.0001	uM
N-[(1R,2S)-2-fluorocyclopropyl]-6-[[1-(6-fluoro-2-pyridinyl)-2-oxo-3-pyridinyl]amino]-8-(methylamino)imidazo[1,2-b]pyridazine-3-carboxamide	1603362: Inhibition of fluorescein-labeled kinase tracer binding to His-TVMV-fused TYK2 JH2 domain (575 to 869 residues) (unknown origin) measured after 90 mins by HTRF assay	ki	<0.0001	uM
6-(cyclopropanecarbonylamino)-4-[3-(5-fluoropyrimidin-2-yl)-2-methoxyanilino]-N-(trideuteriomethyl)pyridine-3-carboxamide	1744162: Inhibition of TYK2 JH2 domain (unknown origin) by HTRF assay based Morrison titration analysis	ki	<0.0001	uM
6-[(2-cyclopropylacetyl)amino]-4-[[3-methoxy-4-(1-methyl-1,2,4-triazol-3-yl)-2-pyridinyl]amino]-N-(trideuteriomethyl)pyridazine-3-carboxamide	2011975: Displacement of fluorescein-labeled kinase tracer from His-TVMV-TYK2 JH2 (575 to 869 residues) (unknown origin) measured after 90 mins by HTRF assay	ic50	<0.0001	uM
6-[[5-(3-hydroxyazetidin-1-yl)-2-pyridinyl]amino]-4-[2-methoxy-3-(1-methyl-1,2,4-triazol-3-yl)anilino]-N-(trideuteriomethyl)pyridazine-3-carboxamide	2029526: Binding affinity to human wild-type partial length TYK2 JH2 (G556 to D888 residues) expressed in mammalian expression system by KINOMEscan assay	kd	<0.0001	uM
N-[4-[(6-methylsulfonyl-2-pyridinyl)amino]-5-pyridin-2-yl-2-pyridinyl]acetamide	2029556: Inhibition of TYK2 JH2 (561 to 860 residues) (unknown origin) by HTRF assay	ic50	<0.0001	uM
N-[4-(3-methylsulfonylanilino)-5-pyridin-2-yl-2-pyridinyl]acetamide	2029556: Inhibition of TYK2 JH2 (561 to 860 residues) (unknown origin) by HTRF assay	ic50	<0.0001	uM
6-(cyclopropanecarbonylamino)-4-[3-[[4-[[(2S)-1,4-dioxan-2-yl]methylamino]phenyl]carbamoyl]-2-methoxyanilino]-N-(trideuteriomethyl)pyridazine-3-carboxamide	1875749: Binding affinity to T7-tagged TYK2 JH2 (unknown origin) expressed in Escherichia coli BL21 cells incubated for 1 hr by qPCR analysis	kd	<0.0001	uM
N-[5-(5-fluoro-2-pyridinyl)-4-[(4-methoxy-6-methylsulfonyl-2-pyridinyl)amino]-2-pyridinyl]acetamide	2029556: Inhibition of TYK2 JH2 (561 to 860 residues) (unknown origin) by HTRF assay	ic50	<0.0001	uM
N-[5-[5-(2-hydroxypropan-2-yl)-2-pyridinyl]-4-[(4-methoxy-6-methylsulfonyl-2-pyridinyl)amino]-2-pyridinyl]acetamide	2029556: Inhibition of TYK2 JH2 (561 to 860 residues) (unknown origin) by HTRF assay	ic50	<0.0001	uM
N-[5-(2,2-dimethyl-3H-[1,4]dioxino[2,3-b]pyridin-6-yl)-4-[(4-methoxy-6-methylsulfonyl-2-pyridinyl)amino]-2-pyridinyl]acetamide	2029556: Inhibition of TYK2 JH2 (561 to 860 residues) (unknown origin) by HTRF assay	ic50	<0.0001	uM
N-[4-[[4-(2-methoxyethoxy)-6-methylsulfonyl-2-pyridinyl]amino]-5-pyridin-2-yl-2-pyridinyl]acetamide	2029556: Inhibition of TYK2 JH2 (561 to 860 residues) (unknown origin) by HTRF assay	ic50	<0.0001	uM
(13R,17R)-24-(methylamino)-7-(trideuteriomethyl)-12-oxa-2,5,6,7,18,22,26,27-octazahexacyclo[18.5.2.13,10.04,8.013,17.023,27]octacosa-1(26),3,5,8,10(28),20,22,24-octaen-19-one	2029546: Binding affinity to TYK2 JH2 (unknown origin)	kd	<0.0001	uM
6-(cyclopropanecarbonylamino)-4-[2-methoxy-3-[5-[[4-(methylsulfonimidoyl)piperazin-1-yl]methyl]-1,2,4-oxadiazol-3-yl]anilino]-N-(trideuteriomethyl)pyridazine-3-carboxamide	2029526: Binding affinity to human wild-type partial length TYK2 JH2 (G556 to D888 residues) expressed in mammalian expression system by KINOMEscan assay	kd	<0.0001	uM
2-(4-amino-2-methoxyphenyl)-7-(cyclopropanecarbonylamino)-N-methyl-1H-pyrrolo[2,3-d]pyridazine-4-carboxamide	2011272: Binding affinity to human recombinant TYK2 (556 to 871 residues) incubated for 10 hrs by microplate reader based analysis	kd	<0.0001	uM
6-(cyclopropanecarbonylamino)-4-[2-methoxy-3-[5-(methylsulfonimidoyl)-4,6-dihydropyrrolo[3,4-c]pyrazol-2-yl]anilino]-N-(trideuteriomethyl)pyridazine-3-carboxamide	2029526: Binding affinity to human wild-type partial length TYK2 JH2 (G556 to D888 residues) expressed in mammalian expression system by KINOMEscan assay	kd	<0.0001	uM
6-[[2-(2,6-difluorophenyl)-5-oxo-6,7-dihydropyrrolo[3,4-b]pyridin-4-yl]amino]-N-ethylpyridine-3-carboxamide	1851014: Inhibition of TYK2 JH1 domain (unknown origin) measured in presence of 10 uM ATP	ki	0.0001	uM
3-fluoro-2-[4-[(5-morpholin-4-yl-2-pyridinyl)amino]-5-oxo-6,7-dihydropyrrolo[3,4-b]pyridin-2-yl]benzonitrile	1851014: Inhibition of TYK2 JH1 domain (unknown origin) measured in presence of 10 uM ATP	ki	0.0001	uM
2-(2,6-difluorophenyl)-4-[[5-(4,4-difluoropiperidin-1-yl)-2-pyridinyl]amino]-6,7-dihydropyrrolo[3,4-b]pyridin-5-one	1851014: Inhibition of TYK2 JH1 domain (unknown origin) measured in presence of 10 uM ATP	ki	0.0001	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, decreases methylation	2
sodium arsenite	decreases expression, increases abundance	2
aristolochic acid I	increases expression	1
FR900359	decreases phosphorylation	1
bisphenol F	decreases methylation	1
moringin	increases expression	1
6-hydroxy-3-O-methylkaempferol 6-O-glucopyranoside	increases expression, increases reaction, increases phosphorylation, decreases reaction	1
triphenyl phosphate	affects expression	1
2,4,5,2’,4’,5’-hexachlorobiphenyl	increases phosphorylation	1
beta-lapachone	decreases expression	1
isoquercitrin	affects expression	1
cobaltous chloride	decreases expression	1
perfluorooctanoic acid	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
10-decarbamoylmitomycin C	decreases phosphorylation	1
perfluorooctane sulfonic acid	decreases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
corosolic acid	increases expression	1
2-palmitoylglycerol	increases expression	1
obeticholic acid	decreases expression	1
perfluorohexanesulfonic acid	decreases expression	1
ICG 001	increases expression	1
ON 01910	decreases phosphorylation	1
ponatinib	decreases activity	1
4-acetylantroquinonol B	decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Interferon alpha-2	increases expression, increases reaction, increases phosphorylation, decreases reaction	1
Temozolomide	increases expression	1
Decitabine	affects cotreatment, decreases expression	1
Arsenic Trioxide	affects cotreatment, decreases expression	1

ChEMBL screening assays

1083 unique, capped per target: 1043 binding, 39 functional, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1218226	Binding	Inhibition of JAK-mediated interferon-gamma/anisomycin-induced Stat1 phosphorylation in human U937 cells by Phospho-Flow cytometry	High-content single-cell drug screening with phosphospecific flow cytometry. — Nat Chem Biol
CHEMBL1963765	Functional	PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: TYK2	PubChem BioAssay data set
CHEMBL4685312	ADMET	Inhibition of recombinant human N-terminal GST-tagged TYK2 cytoplasmic domain (833 to 1187 residues) expressed in baculovirus expression system using TK-substrate-biotin preincubated for 5 mins followed by substrate addition and measured af	Design, synthesis, and pharmacological evaluation of 4- or 6-phenyl-pyrimidine derivatives as novel and selective Janus kinase 3 inhibitors. — Eur J Med Chem

Cellosaurus cell lines

12 cell lines: 9 cancer cell line, 3 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B3KH	Abcam HEK293T TYK2 KO	Transformed cell line	Female
CVCL_D8D7	Ubigene A-549 TYK2 KO	Cancer cell line	Male
CVCL_D8XW	Ubigene HCT 116 TYK2 KO	Cancer cell line	Male
CVCL_D9V7	Ubigene HEK293 TYK2 KO	Transformed cell line	Female
CVCL_E0SH	Ubigene HeLa TYK2 KO	Cancer cell line	Female
CVCL_TV30	HAP1 TYK2 (-) 1	Cancer cell line	Male
CVCL_TV31	HAP1 TYK2 (-) 2	Cancer cell line	Male
CVCL_TV32	HAP1 TYK2 (-) 3	Cancer cell line	Male
CVCL_TV33	HAP1 TYK2 (-) 4	Cancer cell line	Male
CVCL_TV34	HAP1 TYK2 (-) 5	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00001542	PHASE4	COMPLETED	Fluconazole Prophylaxis of Thrush in AIDS
NCT00144157	PHASE4	COMPLETED	Open Label Study of NVP+CBV Treatment in Women Who Have Received sdNVP for the pMTCT of HIV
NCT00162643	PHASE4	UNKNOWN	PI Vs. NNRTI Based Therapy for HIV Advanced Disease
NCT00273988	PHASE4	COMPLETED	Pharmacokinetic Study of Interaction Between Nevirapine and Methadone in HIV-1 Infected, Opioid-dependent Adults
NCT00981318	PHASE4	TERMINATED	Pilot Assessment of Lopinavir/Ritonavir and Maraviroc
NCT01086878	PHASE4	COMPLETED	Safety of Cotrimoxazole in HIV- and HAART-exposed Infants
NCT01090102	PHASE4	COMPLETED	Mesalamine to Reduce T Cell Activation in HIV Infection
NCT01147042	PHASE4	TERMINATED	Biochemical Response to Interferon-Gamma in Subjects With Specific Gene Mutation in Chronic Granulomatous Disease
NCT01230580	PHASE4	UNKNOWN	Protease Inhibitor Monotherapy Versus Ongoing Triple-therapy in the Long Term Management of HIV Infection (PIVOT)
NCT01465958	PHASE4	COMPLETED	Pharmacokinetics, Safety, and Tolerability of Subcutaneous GAMUNEX-C in Pediatric Subjects With Primary Immunodeficiency
NCT02274662	PHASE4	COMPLETED	Expanded Access Protocol Thymus Transplantation
NCT02348177	PHASE4	COMPLETED	Pharmacokinetics of Lopinavir/Ritonavir Superboosting in Infants and Young Children Co-infected With HIV and TB
NCT02396979	PHASE4	COMPLETED	Intervention of HIV, Drug Use and the Criminal Justice System in Malaysia
NCT02490956	PHASE4	UNKNOWN	Diagnostic Immunization With Rabies Vaccine in Patients With PID
NCT02503293	PHASE4	COMPLETED	A Study to Compare Quality of Life and Satisfaction in Primary Immunodeficient Patients Treated With Subcutaneous Injections of Gammanorm® 165 mg/mL Administered With Two Different Delivery Devices: Injections Using Pump or Rapid Push
NCT02881437	PHASE4	COMPLETED	IgG Level in Primary Immunodeficiency Switching From Standard SCIG to Every Other Week HyQvia
NCT03033745	PHASE4	COMPLETED	Safety and Tolerability of Higher Infusion Parameters of IgPro20 (Hizentra) in Subjects With Primary Immunodeficiency (PID)
NCT03677557	PHASE4	UNKNOWN	Safety, Tolerability, Patient Satisfaction and Cost of 16.5% Subcutaneous Immunoglobulin (Cutaquig®) Treatment
NCT04192487	PHASE4	COMPLETED	Effects of Crofelemer on the Gut Microbiome in Healthy Volunteers and in HIV+ Patients With Non-Infectious Diarrhea
NCT04566692	PHASE4	COMPLETED	A Study to Evaluate IGSC 20% Biweekly Dosing in Treatment-Experienced Participants and Loading/Maintenance Dosing in Treatment-Naïve Participants With Primary Immunodeficiency
NCT05493969	PHASE4	NOT_YET_RECRUITING	Efficacy and Tolerability of DTG Plus 3TC in HIV Infected Adults With Virologically Suppression and TDF Toxicity
NCT06576024	PHASE4	COMPLETED	Immunogenicity and Safety of Inactivated Hepatitis A Vaccine in HIV-infected People
NCT06634641	PHASE4	RECRUITING	Clozapine-related Immunodeficiency in Parkinsons Disease
NCT07076446	PHASE4	ACTIVE_NOT_RECRUITING	An Open-label, Multicenter Study to Assess the Pharmacokinetics (PK), Safety, and Tolerability of Subcutaneous IgPro20 in Immunoglobulin (IG) Treatment-naïve Participants With Primary Immunodeficiency (PID)
NCT00000118	PHASE3	COMPLETED	Ganciclovir Implant Study for Cytomegalovirus Retinitis
NCT00000134	PHASE3	COMPLETED	Studies of the Ocular Complications of AIDS (SOCA)–Cytomegalovirus Retinitis Retreatment Trial (CRRT)
NCT00000590	PHASE3	COMPLETED	Anti-HIV Immunoglobulin (HIVIG) in Prevention of Maternal-Fetal HIV Transmission (Pediatric ACTG Protocol 185)
NCT00001267	PHASE3	COMPLETED	A Randomized Pilot Study for the Treatment of AIDS or AIDS Related Complex With an Alternating or Simultaneous Combination Regimen of AZT and 2’,3’-Dideoxyinosine
NCT00001646	PHASE3	COMPLETED	Voriconazole vs. Amphotericin B in the Treatment of Invasive Aspergillosis
NCT00144183	PHASE3	COMPLETED	A Study of Single Dose Nevirapine (NVP) Combined With Combivir® for the Prevention of Mother to Child Transmission (pMTCT) - Treatment Options Preservation Study (TOPS)
NCT00243568	PHASE3	WITHDRAWN	Vicriviroc, a CCR5 Inhibitor, Added to an Optimized Antiretroviral Therapy for Previously Treated HIV (VICTOR-E2) (Study P04285
NCT00278954	PHASE3	COMPLETED	Efficacy, Safety and Pharmacokinetics of Gammaplex in Primary Immunodeficiency Diseases.
NCT00474370	PHASE3	COMPLETED	Vicriviroc in HIV-Treatment Experienced Subjects (Study P04889AM8)(COMPLETED)
NCT00478231	PHASE3	COMPLETED	Multicenter, Safety Study Of Maraviroc
NCT00523211	PHASE3	COMPLETED	Vicriviroc in HIV-Treatment Experienced Subjects (Study P04405AM5)
NCT00698334	PHASE3	COMPLETED	Efficacy of Thrice Weekly Directly Observed Treatment, Short-course (DOTS) in HIV-associated Tuberculosis
NCT00966160	PHASE3	COMPLETED	CD4 Cell Recovery in HIV-1 Patients Comparing 2 Treatment Regimes
NCT01363011	PHASE3	COMPLETED	Cobicistat-containing Highly Active Antiretroviral Regimens in HIV-1 Infected Patients With Mild to Moderate Renal Impairment
NCT01440569	PHASE3	COMPLETED	Safety and Efficacy of Cobicistat-boosted Darunavir in HIV Infected Adults
NCT01475838	PHASE3	COMPLETED	Study to Evaluate Switching From Regimens Consisting of a Ritonavir-boosted Protease Inhibitor Plus Emtricitabine/Tenofovir Fixed-Dose Combination to the Elvitegravir/Cobicistat/Emtricitabine/Tenofovir DF Single-Tablet Regimen in Virologically Suppressed, HIV-1 Infected Patients