Fenebrutinib

Summary

Fenebrutinib (CHEMBL4065122) is a phase-3 clinical-stage small molecule targeting BTK; indicated across 6 conditions including chronic progressive multiple sclerosis and multiple sclerosis.

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• Targets: 1 (BTK)
• Indications: 6 conditions
• Clinical trials: 17
• Chemistry: 664.8 Da · C37H44N8O4

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL4065122
Name	Fenebrutinib
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	86567195
Molecular formula	C37H44N8O4
Molecular weight	664.8
InChIKey	WNEODWDFDXWOLU-QHCPKHFHSA-N

SMILES: C[C@H]1CN(CCN1C2=CN=C(C=C2)NC3=CC(=CN(C3=O)C)C4=C(C(=NC=C4)N5CCN6C7=C(CC(C7)(C)C)C=C6C5=O)CO)C8COC8

IUPAC name: 10-[3-(hydroxymethyl)-4-[1-methyl-5-[[5-[(2S)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl]-2-pyridinyl]amino]-6-oxo-3-pyridinyl]-2-pyridinyl]-4,4-dimethyl-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-9-one

Also known as: Fenebrutinib, G-02599853, G02599853, Gdc-0853, GDC-0853, RG-7845, RG7845, RO-7010939, RO7010939, FENEBRUTINIB, FenebrutinibÊ, FenebrutinibÂ

Patent coverage: 290 distinct patent families (809 SureChEMBL compound mentions), from 3 matched compound structure(s). One matched structure accounts for 699 (86%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
BTK	Bruton tyrosine kinase	Inhibition		0.7%	Q06187

Broader ChEMBL bioactivity targets: 1 (assay-derived). Sample: Tyrosine-protein kinase BTK.

Bioactivity

ChEMBL activities: 19 potent at pChembl ≥ 5 of 19 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
BTK	9.46	Kd	0.35	nM	CHEMBL_ACT_25536954
BTK	9.05	Ki	0.9	nM	CHEMBL_ACT_24773273
BTK	9.04	Ki	0.91	nM	CHEMBL_ACT_18109178
BTK	8.92	IC50	1.2	nM	CHEMBL_ACT_18109379
BTK	8.89	IC50	1.3	nM	CHEMBL_ACT_18109382
BTK	8.89	Ki	1.3	nM	CHEMBL_ACT_18109406
BTK	8.85	IC50	1.4	nM	CHEMBL_ACT_18109380
BTK	8.8	Ki	1.6	nM	CHEMBL_ACT_18109405
BTK	8.8	Ki	1.6	nM	CHEMBL_ACT_24773315
BTK	8.64	IC50	2.3	nM	CHEMBL_ACT_20679903
BTK	8.64	IC50	2.3	nM	CHEMBL_ACT_25638891
BTK	8.51	IC50	3.1	nM	CHEMBL_ACT_18109381
BTK	8.47	Ki	3.4	nM	CHEMBL_ACT_18109408
BTK	8.1	IC50	8	nM	CHEMBL_ACT_18109209
BTK	8.1	IC50	8	nM	CHEMBL_ACT_20679966
BTK	7.96	IC50	11	nM	CHEMBL_ACT_18109378
BTK	7.92	IC50	12.1	nM	CHEMBL_ACT_25536959
BTK	7.9	Ki	12.6	nM	CHEMBL_ACT_18109407
BTK	7.51	IC50	30.7	nM	CHEMBL_ACT_18109386

Target pathways

Aggregated over 1 target gene(s): BTK.

Top Reactome pathways

45 total, by targets touching each:

Pathway	Targets	Genes
ER-Phagosome pathway	1	BTK
Antigen processing-Cross presentation	1	BTK
Adaptive Immune System	1	BTK
Signal Transduction	1	BTK
Disease	1	BTK
Toll Like Receptor 4 (TLR4) Cascade	1	BTK
MyD88:MAL(TIRAP) cascade initiated on plasma membrane	1	BTK
Toll Like Receptor TLR1:TLR2 Cascade	1	BTK
Toll Like Receptor TLR6:TLR2 Cascade	1	BTK
Innate Immune System	1	BTK
Immune System	1	BTK
Toll-like Receptor Cascades	1	BTK
Toll Like Receptor 2 (TLR2) Cascade	1	BTK
Signaling by Rho GTPases	1	BTK
RHO GTPase Effectors	1	BTK
Fcgamma receptor (FCGR) dependent phagocytosis	1	BTK
Regulation of actin dynamics for phagocytic cup formation	1	BTK
DAP12 interactions	1	BTK
DAP12 signaling	1	BTK
Fc epsilon receptor (FCERI) signaling	1	BTK
FCERI mediated Ca+2 mobilization	1	BTK
Signaling by GPCR	1	BTK
GPCR downstream signalling	1	BTK
G-protein beta:gamma signalling	1	BTK
G alpha (q) signalling events	1	BTK
G alpha (12/13) signalling events	1	BTK
Diseases of Immune System	1	BTK
Diseases associated with the TLR signaling cascade	1	BTK
MyD88 deficiency (TLR2/4)	1	BTK
IRAK4 deficiency (TLR2/4)	1	BTK

Dominant GO biological processes

GO term	Targets
neutrophil homeostasis	1
positive regulation of type III hypersensitivity	1
positive regulation of type I hypersensitivity	1
adaptive immune response	1
B cell affinity maturation	1
histamine secretion by mast cell	1
positive regulation of immunoglobulin production	1
regulation of B cell cytokine production	1
MyD88-dependent toll-like receptor signaling pathway	1
regulation of B cell apoptotic process	1
mesoderm development	1
peptidyl-tyrosine phosphorylation	1
calcium-mediated signaling	1
proteoglycan catabolic process	1
negative regulation of B cell proliferation	1

Indications & clinical

Indications

6 indications (0 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
chronic progressive multiple sclerosis	3	MONDO:0005284	EFO:0003840
multiple sclerosis	3	MONDO:0005301	MONDO:0005301
rheumatoid arthritis	2	MONDO:0008383	EFO:0000685
urticaria	2	MONDO:0005492	EFO:0005531
systemic lupus erythematosus	2	MONDO:0007915	MONDO:0007915
autoimmune disease	1	MONDO:0007179	EFO:0005809

Clinical trials

Total trials: 17.

Phase distribution

Phase	Trials
PHASE2	8
PHASE1	6
PHASE3	3

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04544449	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Evaluate the Efficacy and Safety of Fenebrutinib Compared With Ocrelizumab in Adult Participants With Primary Progressive Multiple Sclerosis
NCT04586010	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Evaluate the Efficacy and Safety of Fenebrutinib Compared With Teriflunomide in Relapsing Multiple Sclerosis (RMS)
NCT04586023	PHASE3	ACTIVE_NOT_RECRUITING	Study to Evaluate the Efficacy and Safety of Fenebrutinib Compared With Teriflunomide in Relapsing Multiple Sclerosis (RMS)
NCT05119569	PHASE2	ACTIVE_NOT_RECRUITING	A Study to Investigate the Efficacy of Fenebrutinib in Relapsing Multiple Sclerosis (RMS)
NCT07161258	PHASE2	RECRUITING	A Pharmacokinetics (PK), Pharmacodynamics (PD), Safety and Tolerability Study of Fenebrutinib in Children and Adolescents With Relapsing Multiple Sclerosis (RMS)
NCT02833350	PHASE2	COMPLETED	Safety and Efficacy Study of GDC-0853 Compared With Placebo and Adalimumab in Participants With Rheumatoid Arthritis (RA)
NCT02908100	PHASE2	COMPLETED	A Study of the Safety and Efficacy of GDC-0853 in Participants With Moderate to Severe Active Systemic Lupus Erythematosus
NCT02983227	PHASE2	COMPLETED	A Study to Evaluate the Long-Term Safety and Efficacy of GDC-0853 in Participants With Moderate to Severe Rheumatoid Arthritis Enrolled in Study GA29350
NCT03137069	PHASE2	COMPLETED	A Study of GDC-0853 in Participants With Refractory Chronic Spontaneous Urticaria (CSU).
NCT03407482	PHASE2	TERMINATED	An Extension Study of GDC-0853 in Participants With Moderate to Severe Active Systemic Lupus Erythematosus
NCT03693625	PHASE2	TERMINATED	A Study to Evaluate the Long-term Safety and Efficacy of Fenebrutinib in Participants Previously Enrolled in a Fenebrutinib Chronic Spontaneous Urticaria (CSU) Study
NCT01991184	PHASE1	COMPLETED	A Study of GDC-0853 in Patients With Resistant B-Cell Lymphoma or Chronic Lymphocytic Leukemia.
NCT02699710	PHASE1	COMPLETED	Effect of Food, Rabeprazole, Methotrexate and Formulation on the Pharmacokinetics (PK) of GDC-0853 and the Effect of GDC-0853 on the PK of Methotrexate in Healthy Subjects
NCT03174041	PHASE1	COMPLETED	A Drug-Drug Interaction Study Between GDC-0853 and Midazolam, Itraconazole, Rosuvastatin, and Simvastatin
NCT03188783	PHASE1	COMPLETED	A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of GDC-0853 in Healthy Japanese and Caucasian Participants
NCT03290703	PHASE1	COMPLETED	A Study to Investigate the Effect of Formulation, Food, and Rabeprazole on the Pharmacokinetics (PK) of GDC-0853 in Healthy Participants
NCT03596632	PHASE1	COMPLETED	Study Investigating a Single Oral Dose of Fenebrutinib in Healthy Volunteers

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No PharmGKB pharmacogenomic data curated for this drug.

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

80 molecules share ≥1 primary target. Top 60 by shared-target count:

Molecule	Source	Status	Shared targets
CRIZOTINIB	ChEMBL + PubChem	Phase 4 (approved)	BTK
RITLECITINIB	ChEMBL + PubChem	Phase 4 (approved)	BTK
ACALABRUTINIB	ChEMBL	Phase 4 (approved)	BTK
BOSUTINIB	ChEMBL	Phase 4 (approved)	BTK
BRIGATINIB	ChEMBL	Phase 4 (approved)	BTK
CERITINIB	ChEMBL	Phase 4 (approved)	BTK
DASATINIB	ChEMBL	Phase 4 (approved)	BTK
ENTRECTINIB	ChEMBL	Phase 4 (approved)	BTK
FEDRATINIB	ChEMBL	Phase 4 (approved)	BTK
FUTIBATINIB	ChEMBL	Phase 4 (approved)	BTK
IBRUTINIB	ChEMBL	Phase 4 (approved)	BTK
MITOXANTRONE	ChEMBL	Phase 4 (approved)	BTK
NERATINIB	ChEMBL	Phase 4 (approved)	BTK
NINTEDANIB	ChEMBL	Phase 4 (approved)	BTK
OLMUTINIB	ChEMBL	Phase 4 (approved)	BTK
OSIMERTINIB	ChEMBL	Phase 4 (approved)	BTK
PIRTOBRUTINIB	ChEMBL	Phase 4 (approved)	BTK
PONATINIB	ChEMBL	Phase 4 (approved)	BTK
SUNITINIB	ChEMBL	Phase 4 (approved)	BTK
TIRABRUTINIB	ChEMBL	Phase 4 (approved)	BTK
VANDETANIB	ChEMBL	Phase 4 (approved)	BTK
ZANUBRUTINIB	ChEMBL	Phase 4 (approved)	BTK
ABIVERTINIB	ChEMBL	Phase 3	BTK
ALISERTIB	ChEMBL	Phase 3	BTK
CANERTINIB	ChEMBL	Phase 3	BTK
CEDIRANIB	ChEMBL	Phase 3	BTK
DOVITINIB	ChEMBL	Phase 3	BTK
ENTOSPLETINIB	ChEMBL	Phase 3	BTK
EVOBRUTINIB	ChEMBL	Phase 3	BTK
LESTAURTINIB	ChEMBL	Phase 3	BTK
NEMTABRUTINIB	ChEMBL	Phase 3	BTK
ORELABRUTINIB	ChEMBL	Phase 3	BTK
POZIOTINIB	ChEMBL	Phase 3	BTK
PYROTINIB	ChEMBL	Phase 3	BTK
REMIBRUTINIB	ChEMBL	Phase 3	BTK
RILZABRUTINIB	ChEMBL	Phase 3	BTK
ROCILETINIB	ChEMBL	Phase 3	BTK
SARACATINIB	ChEMBL	Phase 3	BTK
TESEVATINIB	ChEMBL	Phase 3	BTK
TOLEBRUTINIB	ChEMBL	Phase 3	BTK
APITOLISIB	ChEMBL	Phase 2	BTK
AT-9283	ChEMBL	Phase 2	BTK
ATUZABRUTINIB	ChEMBL	Phase 2	BTK
BIIB-091	ChEMBL	Phase 2	BTK
BMS-754807	ChEMBL	Phase 2	BTK
BMS-919373	ChEMBL	Phase 2	BTK
BMS-986142	ChEMBL	Phase 2	BTK
BRANEBRUTINIB	ChEMBL	Phase 2	BTK
CENISERTIB	ChEMBL	Phase 2	BTK
CEP-11981	ChEMBL	Phase 2	BTK
DANUSERTIB	ChEMBL	Phase 2	BTK
DEFOSBARASERTIB	ChEMBL	Phase 2	BTK
EDRALBRUTINIB	ChEMBL	Phase 2	BTK
ELSUBRUTINIB	ChEMBL	Phase 2	BTK
FORETINIB	ChEMBL	Phase 2	BTK
ILORASERTIB	ChEMBL	Phase 2	BTK
MILREBRUTINIB	ChEMBL	Phase 2	BTK
PELITINIB	ChEMBL	Phase 2	BTK
POSELTINIB	ChEMBL	Phase 2	BTK
R-406	ChEMBL	Phase 2	BTK