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fenebrutinib   Click here for help

GtoPdb Ligand ID: 9299

Synonyms: Example 130 [US20140194408] | GDC-0853 | GDC0853 | RG-7845 | RG7845
PDB Ligand Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: Fenebrutinib (RG7845, GDC-0853) is a reversible noncovalent Bruton's tyrosine kinase (BTK) inhibitor, that was proposed for therapeutic potential in difficult-to-treat autoimmune diseases, including multiple sclerosis [9]. The compound is claimed in patent WO2013067274 [3]. It interacts with BTK in its inactive confirmation.

fenebrutinib 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 7
Topological polar surface area 120.99
Molecular weight 664.35
XLogP 5.44
No. Lipinski's rules broken 1

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 OCc1c(ccnc1N1CCn2c(C1=O)cc1c2CC(C1)(C)C)c1cc(Nc2ccc(cn2)N2CCN(CC2C)C2COC2)c(=O)n(c1)C
Isomeric SMILES OCc1c(ccnc1N1CCn2c(C1=O)cc1c2CC(C1)(C)C)c1cc(Nc2ccc(cn2)N2CCN(C[C@@H]2C)C2COC2)c(=O)n(c1)C
InChI InChI=1S/C37H44N8O4/c1-23-18-42(27-21-49-22-27)9-10-43(23)26-5-6-33(39-17-26)40-30-13-25(19-41(4)35(30)47)28-7-8-38-34(29(28)20-46)45-12-11-44-31(36(45)48)14-24-15-37(2,3)16-32(24)44/h5-8,13-14,17,19,23,27,46H,9-12,15-16,18,20-22H2,1-4H3,(H,39,40)/t23-/m0/s1
InChI Key WNEODWDFDXWOLU-QHCPKHFHSA-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. Akinleye A, Chen Y, Mukhi N, Song Y, Liu D. (2013)
Ibrutinib and novel BTK inhibitors in clinical development.
J Hematol Oncol, 6: 59. [PMID:23958373]
2. Bar-Or A, Dufek M, Budincevic H, Drulovic J, Habek M, Hua LH, Weber MS, Thomas P, Napieralski J, Mitzner MC et al.. (2025)
Safety and efficacy of fenebrutinib in relapsing multiple sclerosis (FENopta): a multicentre, double-blind, randomised, placebo-controlled, phase 2 trial and open-label extension study.
Lancet Neurol, 24 (8): 656-666. [PMID:40683275]
3. Crawford JJ, Ortwine DF, Wei B, Young WB. (2013)
Heteroaryl pyridone and aza-pyridone compounds as inhibitors of btk activity.
Patent number: WO2013067274. Assignee: Genentech, Inc.. Priority date: 03/11/2011. Publication date: 10/05/2013.
4. Herman AE, Chinn LW, Kotwal SG, Murray ER, Zhao R, Florero M, Lin A, Moein A, Wang R, Bremer M et al.. (2018)
Safety, Pharmacokinetics, and Pharmacodynamics in Healthy Volunteers Treated With GDC-0853, a Selective Reversible Bruton's Tyrosine Kinase Inhibitor.
Clin Pharmacol Ther, 103 (6): 1020-1028. [PMID:29484638]
5. Isenberg D, Furie R, Jones NS, Guibord P, Galanter J, Lee C, McGregor A, Toth B, Rae J, Hwang O et al.. (2021)
Efficacy, Safety, and Pharmacodynamic Effects of the Bruton's Tyrosine Kinase Inhibitor Fenebrutinib (GDC-0853) in Systemic Lupus Erythematosus: Results of a Phase II, Randomized, Double-Blind, Placebo-Controlled Trial.
Arthritis Rheumatol, 73 (10): 1835-1846. [PMID:34042314]
6. Meglio M. 
Phase 2 Data Highlight Fenebrutinib’s Impact on Brain Lesions in Relapsing Multiple Sclerosis.
Accessed on 25/07/2023. Modified on 25/07/2023. NeurologyLive, https://www.neurologylive.com/view/phase-2-data-highlight-fenebrutinib-impact-brain-lesions-in-relapsing-multiple-sclerosis
7. Metz M, Sussman G, Gagnon R, Staubach P, Tanus T, Yang WH, Lim JJ, Clarke HJ, Galanter J, Chinn LW et al.. (2021)
Fenebrutinib in H1 antihistamine-refractory chronic spontaneous urticaria: a randomized phase 2 trial.
Nat Med, 27 (11): 1961-1969. [PMID:34750553]
8. Musumeci F, Sanna M, Greco C, Giacchello I, Fallacara AL, Amato R, Schenone S. (2017)
Pyrrolo[2,3-d]pyrimidines active as Btk inhibitors.
Expert Opin Ther Pat, 27 (12): 1305-1318. [PMID:28705083]
9. Shulga O, Chabanova A, Kotsiuba O. (2023)
Bruton's tyrosine kinase inhibitors in the treatment of multiple sclerosis.
Postep Psychiatr Neurol, 32 (1): 23-30. [PMID:37287740]