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BIIB091   Click here for help

GtoPdb Ligand ID: 11791

Synonyms: BIIB-091 | compound 51 [PMID: 34734694]
PDB Ligand Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: BIIB091 was disclosed as an orthosteric, ATP-competitive inhibitor of the Tec family kinase, Bruton's tyrosine kinase (BTK) [2]. The molecule binds within the enzyme's "H3" pocket (location of Tyr-551).Additional interactsions with two nonconserved backbone residues (Leu-542 and Ser-543) confer selectivity for BTK versus the other Tec family kinases.

It is being investigated by Biogen to block the inflammatory processes that drive neurodegeneration in multiple sclerosis. The molecule with no specified stereo centres is represented by compound 71 [WO2018191577A1].
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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

BIIB091 is commercially available from our sponsors

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 10
Hydrogen bond donors 2
Rotatable bonds 8
Topological polar surface area 127.91
Molecular weight 542.29
XLogP 2.6
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 Cn1ncc(c1)Nc1nccc(n1)c1ccc2c(c1)CN(CC[C@H]2NC(=O)c1nnn(c1)C(C)(C)C)C1COC1
Isomeric SMILES O=C(c1cn(C(C)(C)C)nn1)N[C@H]1c2ccc(c3ccnc(Nc4cn(C)nc4)n3)cc2CN(C2COC2)CC1
InChI InChI=1S/C28H34N10O2/c1-28(2,3)38-15-25(34-35-38)26(39)32-24-8-10-37(21-16-40-17-21)13-19-11-18(5-6-22(19)24)23-7-9-29-27(33-23)31-20-12-30-36(4)14-20/h5-7,9,11-12,14-15,21,24H,8,10,13,16-17H2,1-4H3,(H,32,39)(H,29,31,33)/t24-/m1/s1
InChI Key JSAQBOQCZJHWMA-XMMPIXPASA-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. Bame E, Tang H, Burns JC, Arefayene M, Michelsen K, Ma B, Marx I, Prince R, Roach AM, Poreci U et al.. (2021)
Next-generation Bruton's tyrosine kinase inhibitor BIIB091 selectively and potently inhibits B cell and Fc receptor signaling and downstream functions in B cells and myeloid cells.
Clin Transl Immunology, 10 (6): e1295. [PMID:34141433]
2. Hopkins BT, Bame E, Bajrami B, Black C, Bohnert T, Boiselle C, Burdette D, Burns JC, Delva L, Donaldson D et al.. (2022)
Discovery and Preclinical Characterization of BIIB091, a Reversible, Selective BTK Inhibitor for the Treatment of Multiple Sclerosis.
J Med Chem, 65 (2): 1206-1224. [PMID:34734694]
3. Li R, Tang H, Burns JC, Hopkins BT, Le Coz C, Zhang B, de Barcelos IP, Romberg N, Goldstein AC, Banwell BL et al.. (2022)
BTK inhibition limits B-cell-T-cell interaction through modulation of B-cell metabolism: implications for multiple sclerosis therapy.
Acta Neuropathol, 143 (4): 505-521. [PMID:35303161]