TAK-828F   Click here for help

GtoPdb Ligand ID: 9867

Synonyms: compound 10 [PMID: 29510038] | TAK-828 | TAK828F
PDB Ligand Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: TAK-828F is a potent, selective, and orally available novel retinoic acid receptor-related orphan receptor γt (RORγt) inverse agonist [6,12]. The X-ray structure of RORγt in complex with TAK-828F has been submitted to the Protein Data Bank (6BR3).
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species
2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 7
Hydrogen bond donors 2
Rotatable bonds 8
Topological polar surface area 108.83
Molecular weight 509.23
XLogP 3.23
No. Lipinski's rules broken 0

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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Canonical SMILES COc1ccc2c(n1)CCN(C2C(=O)Nc1cc(F)c2c(c1)CCC2(C)C)C(=O)C1CC(C1)CC(=O)O
Isomeric SMILES COc1ccc2c(n1)CCN([C@H]2C(=O)Nc1cc(F)c2c(c1)CCC2(C)C)C(=O)[C@@H]1C[C@@H](C1)CC(=O)O
InChI InChI=1S/C28H32FN3O5/c1-28(2)8-6-16-13-18(14-20(29)24(16)28)30-26(35)25-19-4-5-22(37-3)31-21(19)7-9-32(25)27(36)17-10-15(11-17)12-23(33)34/h4-5,13-15,17,25H,6-12H2,1-3H3,(H,30,35)(H,33,34)/t15-,17+,25-/m1/s1
InChI Key ICMFYVOUDGRBLG-VFHHBZAHSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
References
1. Annunziato F, Cosmi L, Santarlasci V, Maggi L, Liotta F, Mazzinghi B, Parente E, Filì L, Ferri S, Frosali F et al.. (2007)
Phenotypic and functional features of human Th17 cells.
J Exp Med, 204 (8): 1849-61. [PMID:17635957]
2. Beringer A, Noack M, Miossec P. (2016)
IL-17 in Chronic Inflammation: From Discovery to Targeting.
Trends Mol Med, 22 (3): 230-241. [PMID:26837266]
3. Campa M, Mansouri B, Warren R, Menter A. (2016)
A Review of Biologic Therapies Targeting IL-23 and IL-17 for Use in Moderate-to-Severe Plaque Psoriasis.
Dermatol Ther (Heidelb), 6 (1): 1-12. [PMID:26714681]
4. Ivanov II, McKenzie BS, Zhou L, Tadokoro CE, Lepelley A, Lafaille JJ, Cua DJ, Littman DR. (2006)
The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells.
Cell, 126 (6): 1121-33. [PMID:16990136]
5. Kebir H, Ifergan I, Alvarez JI, Bernard M, Poirier J, Arbour N, Duquette P, Prat A. (2009)
Preferential recruitment of interferon-gamma-expressing TH17 cells in multiple sclerosis.
Ann Neurol, 66 (3): 390-402. [PMID:19810097]
6. Kono M, Ochida A, Oda T, Imada T, Banno Y, Taya N, Masada S, Kawamoto T, Yonemori K, Nara Y et al.. (2018)
Discovery of [ cis-3-({(5 R)-5-[(7-Fluoro-1,1-dimethyl-2,3-dihydro-1 H-inden-5-yl)carbamoyl]-2-methoxy-7,8-dihydro-1,6-naphthyridin-6(5 H)-yl}carbonyl)cyclobutyl]acetic Acid (TAK-828F) as a Potent, Selective, and Orally Available Novel Retinoic Acid Receptor-Related Orphan Receptor γt Inverse Agonist.
J Med Chem, 61 (7): 2973-2988. [PMID:29510038]
7. Kotake S, Udagawa N, Takahashi N, Matsuzaki K, Itoh K, Ishiyama S, Saito S, Inoue K, Kamatani N, Gillespie MT et al.. (1999)
IL-17 in synovial fluids from patients with rheumatoid arthritis is a potent stimulator of osteoclastogenesis.
J Clin Invest, 103 (9): 1345-52. [PMID:10225978]
8. Miossec P, Kolls JK. (2012)
Targeting IL-17 and TH17 cells in chronic inflammation.
Nat Rev Drug Discov, 11 (10): 763-76. [PMID:23023676]
9. Moran EM. 
Th17 cells- Bitesized immunology.
Accessed on 27/03/2018. Modified on 27/03/2018. www.immunology.org, https://www.immunology.org/public-information/bitesized-immunology/cells/th17-cells
10. Nair RP, Duffin KC, Helms C, Ding J, Stuart PE, Goldgar D, Gudjonsson JE, Li Y, Tejasvi T, Feng BJ et al.. (2009)
Genome-wide scan reveals association of psoriasis with IL-23 and NF-kappaB pathways.
Nat Genet, 41 (2): 199-204. [PMID:19169254]
11. Rovedatti L, Kudo T, Biancheri P, Sarra M, Knowles CH, Rampton DS, Corazza GR, Monteleone G, Di Sabatino A, Macdonald TT. (2009)
Differential regulation of interleukin 17 and interferon gamma production in inflammatory bowel disease.
Gut, 58 (12): 1629-36. [PMID:19740775]
12. Shibata A, Uga K, Sato T, Sagara M, Igaki K, Nakamura Y, Ochida A, Kono M, Shirai J, Yamamoto S et al.. (2018)
Pharmacological inhibitory profile of TAK-828F, a potent and selective orally available RORγt inverse agonist.
Biochem Pharmacol, 150: 35-45. [PMID:29369782]
13. Wilke CM, Bishop K, Fox D, Zou W. (2011)
Deciphering the role of Th17 cells in human disease.
Trends Immunol, 32 (12): 603-11. [PMID:21958759]