Remibrutinib

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Summary

Remibrutinib (CHEMBL4483575) is a phase-3 clinical-stage small molecule (ATC L04AA60) targeting BTK; indicated across 6 conditions including multiple sclerosis and immune system disorder.

At a glance

  • Status: Max clinical phase 3 (not approved)
  • Modality: Small molecule
  • ATC class: L04AA60
  • Targets: 1 (BTK)
  • Indications: 6 conditions
  • Clinical trials: 14
  • Chemistry: 507.5 Da · C27H27F2N5O3

Identifiers

Drug identity and classification

FieldValue
ChEMBL IDCHEMBL4483575
NameRemibrutinib
TypeSmall molecule
Max phase3
FDA approvedno
PubChem CID118107483
ATCL04AA60
Molecular formulaC27H27F2N5O3
Molecular weight507.5
InChIKeyCUABMPOJOBCXJI-UHFFFAOYSA-N

SMILES: CC1=C(C=C(C=C1NC(=O)C2=C(C=C(C=C2)C3CC3)F)F)C4=C(C(=NC=N4)N)OCCN(C)C(=O)C=C

IUPAC name: N-[3-[6-amino-5-[2-[methyl(prop-2-enoyl)amino]ethoxy]pyrimidin-4-yl]-5-fluoro-2-methylphenyl]-4-cyclopropyl-2-fluorobenzamide

Also known as: Remibrutinib, REMIBRUTINIB

Patent coverage: 219 distinct patent families (569 SureChEMBL compound mentions), from 4 matched compound structure(s). 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).

GeneTargetActionpAffinityCancer dependencyUniProt
BTKBruton tyrosine kinaseInhibition90.7%Q06187

Broader ChEMBL bioactivity targets: 13 (assay-derived). Sample: Receptor tyrosine-protein kinase erbB-2, Epidermal growth factor receptor, Tyrosine-protein kinase JAK3, Tyrosine-protein kinase Blk, Voltage-gated inwardly rectifying potassium channel KCNH2, Tyrosine-protein kinase ITK/TSK, Receptor tyrosine-protein kinase erbB-4, Phosphatidylinositol 4-kinase beta, Cytoplasmic tyrosine-protein kinase BMX, Tyrosine-protein kinase Tec.

Bioactivity

ChEMBL activities: 18 potent at pChembl ≥ 5 of 25 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

TargetpChemblTypeValueUnitActivity ID
BTK9.62Kd0.24nMCHEMBL_ACT_24797372
BTK9.2Kd0.63nMCHEMBL_ACT_19061180
BTK9IC501nMCHEMBL_ACT_26665913
BTK9IC501nMCHEMBL_ACT_27777620
BTK9IC501nMCHEMBL_ACT_28555112
BTK9IC501nMCHEMBL_ACT_29021183
BTK8.92IC501.2nMCHEMBL_ACT_24797235
BTK8.89IC501.3nMCHEMBL_ACT_19061016
BTK8.6IC502.5nMCHEMBL_ACT_19061046
BTK7.75IC5018nMCHEMBL_ACT_19061074
BTK7.17IC5067nMCHEMBL_ACT_19061320
TEC7.11Kd77nMCHEMBL_ACT_24797396
TEC6.96Kd110nMCHEMBL_ACT_19061192
BMX6.27Kd540nMCHEMBL_ACT_19061186
BMX5.96Kd1100nMCHEMBL_ACT_24797366
KCNH25.85IC501400nMCHEMBL_ACT_19061276
PI4KB5.51IC503100nMCHEMBL_ACT_19061426
ABCB115.18IC506600nMCHEMBL_ACT_19061427

Target pathways

Aggregated over 1 target gene(s): BTK.

Top Reactome pathways

45 total, by targets touching each:

PathwayTargetsGenes
ER-Phagosome pathway1BTK
Antigen processing-Cross presentation1BTK
Adaptive Immune System1BTK
Signal Transduction1BTK
Disease1BTK
Toll Like Receptor 4 (TLR4) Cascade1BTK
MyD88:MAL(TIRAP) cascade initiated on plasma membrane1BTK
Toll Like Receptor TLR1:TLR2 Cascade1BTK
Toll Like Receptor TLR6:TLR2 Cascade1BTK
Innate Immune System1BTK
Immune System1BTK
Toll-like Receptor Cascades1BTK
Toll Like Receptor 2 (TLR2) Cascade1BTK
Signaling by Rho GTPases1BTK
RHO GTPase Effectors1BTK
Fcgamma receptor (FCGR) dependent phagocytosis1BTK
Regulation of actin dynamics for phagocytic cup formation1BTK
DAP12 interactions1BTK
DAP12 signaling1BTK
Fc epsilon receptor (FCERI) signaling1BTK
FCERI mediated Ca+2 mobilization1BTK
Signaling by GPCR1BTK
GPCR downstream signalling1BTK
G-protein beta:gamma signalling1BTK
G alpha (q) signalling events1BTK
G alpha (12/13) signalling events1BTK
Diseases of Immune System1BTK
Diseases associated with the TLR signaling cascade1BTK
MyD88 deficiency (TLR2/4)1BTK
IRAK4 deficiency (TLR2/4)1BTK

Dominant GO biological processes

GO termTargets
neutrophil homeostasis1
positive regulation of type III hypersensitivity1
positive regulation of type I hypersensitivity1
adaptive immune response1
B cell affinity maturation1
histamine secretion by mast cell1
positive regulation of immunoglobulin production1
regulation of B cell cytokine production1
MyD88-dependent toll-like receptor signaling pathway1
regulation of B cell apoptotic process1
mesoderm development1
peptidyl-tyrosine phosphorylation1
calcium-mediated signaling1
proteoglycan catabolic process1
negative regulation of B cell proliferation1

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).

IndicationTrial phaseMONDOEFO
multiple sclerosis3MONDO:0005301MONDO:0005301
immune system disorder3MONDO:0005046EFO:0000540
allergic disease2MONDO:0005271MONDO:0005271
Sjogren syndrome2MONDO:0010030EFO:0000699
liver disorder1MONDO:0005154EFO:0001421

1 further indication record had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 14.

Phase distribution

PhaseTrials
PHASE39
PHASE23
PHASE11
Not specified1

Top trials by phase / activity

NCTPhaseStatusTitle
NCT05147220PHASE3ACTIVE_NOT_RECRUITINGEfficacy and Safety of Remibrutinib Compared to Teriflunomide in Participants With Relapsing Multiple Sclerosis (RMS)
NCT05156281PHASE3ACTIVE_NOT_RECRUITINGEfficacy and Safety of Remibrutinib Compared to Teriflunomide in Participants With Relapsing Multiple Sclerosis (RMS)
NCT05976243PHASE3ACTIVE_NOT_RECRUITINGA Study to Investigate Efficacy, Safety, and Tolerability of Remibrutinib Compared With Placebo in Adults With CINDU Inadequately Controlled by H1-antihistamines
NCT06042478PHASE3ACTIVE_NOT_RECRUITINGPhase 3b Study to Assess the Efficacy, Safety, and Tolerability of Remibrutinib in Comparison to Placebo, With Omalizumab as Active Control, in Adult CSU Patients, Followed by an Open-label 52-week Optional Extension.
NCT06744920PHASE3RECRUITINGA Study to Investigate the Efficacy, Safety and Tolerability of Remibrutinib Versus Placebo in Adult Patients With Generalized Myasthenia Gravis
NCT06846281PHASE3RECRUITINGEfficacy and Safety of Remibrutinib After Switching From Ocrelizumab in Participants Living With Relapsing Multiple Sclerosis.
NCT06868212PHASE3RECRUITINGA Study to Evaluate Efficacy of Remibrutinib Compared to Dupilumab at Early Timepoints in Adults With Chronic Spontaneous Urticaria Inadequately Controlled by Second Generation H1-antihistamines
NCT07225504PHASE3RECRUITINGA Study to Evaluate the Efficacy and Safety of Remibrutinib in Secondary Progressive Multiple Sclerosis
NCT07456891PHASE3RECRUITINGRemibrutinib Open Label Roll-over Post-trial Access Protocol
NCT06865651PHASE2RECRUITINGStudy of Remibrutinib (LOU064) Efficacy and Safety and Exploration of Its Mechanism of Action in Participants With Chronic Urticaria
NCT04035668PHASE2TERMINATEDA Phase 2 Study to Evaluate the Safety and Efficacy of LOU064 in Patients With Moderate to Severe Sjögren’s Syndrome
NCT05432388PHASE2COMPLETEDStudy of Efficacy, Safety and Tolerability of Remibrutinib in Adult Participants With an Allergy to Peanuts
NCT07032272PHASE1COMPLETEDA Study to Investigate the Pharmacokinetics and Safety of Remibrutinib in Participants With Severe Renal Impairment Compared to Matched Healthy Participants.
NCT05170724Not specifiedAVAILABLEGlobal Managed Access Program Cohort for Remibrutinib in Adult Patients With Chronic Spontaneous Urticaria

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

No PharmGKB pharmacogenomic data curated for this drug.

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:

MoleculeSourceStatusShared targets
CRIZOTINIBChEMBL + PubChemPhase 4 (approved)BTK
RITLECITINIBChEMBL + PubChemPhase 4 (approved)BTK
ACALABRUTINIBChEMBLPhase 4 (approved)BTK
BOSUTINIBChEMBLPhase 4 (approved)BTK
BRIGATINIBChEMBLPhase 4 (approved)BTK
CERITINIBChEMBLPhase 4 (approved)BTK
DASATINIBChEMBLPhase 4 (approved)BTK
ENTRECTINIBChEMBLPhase 4 (approved)BTK
FEDRATINIBChEMBLPhase 4 (approved)BTK
FUTIBATINIBChEMBLPhase 4 (approved)BTK
IBRUTINIBChEMBLPhase 4 (approved)BTK
MITOXANTRONEChEMBLPhase 4 (approved)BTK
NERATINIBChEMBLPhase 4 (approved)BTK
NINTEDANIBChEMBLPhase 4 (approved)BTK
OLMUTINIBChEMBLPhase 4 (approved)BTK
OSIMERTINIBChEMBLPhase 4 (approved)BTK
PIRTOBRUTINIBChEMBLPhase 4 (approved)BTK
PONATINIBChEMBLPhase 4 (approved)BTK
SUNITINIBChEMBLPhase 4 (approved)BTK
TIRABRUTINIBChEMBLPhase 4 (approved)BTK
VANDETANIBChEMBLPhase 4 (approved)BTK
ZANUBRUTINIBChEMBLPhase 4 (approved)BTK
ABIVERTINIBChEMBLPhase 3BTK
ALISERTIBChEMBLPhase 3BTK
CANERTINIBChEMBLPhase 3BTK
CEDIRANIBChEMBLPhase 3BTK
DOVITINIBChEMBLPhase 3BTK
ENTOSPLETINIBChEMBLPhase 3BTK
EVOBRUTINIBChEMBLPhase 3BTK
FENEBRUTINIBChEMBLPhase 3BTK
LESTAURTINIBChEMBLPhase 3BTK
NEMTABRUTINIBChEMBLPhase 3BTK
ORELABRUTINIBChEMBLPhase 3BTK
POZIOTINIBChEMBLPhase 3BTK
PYROTINIBChEMBLPhase 3BTK
RILZABRUTINIBChEMBLPhase 3BTK
ROCILETINIBChEMBLPhase 3BTK
SARACATINIBChEMBLPhase 3BTK
TESEVATINIBChEMBLPhase 3BTK
TOLEBRUTINIBChEMBLPhase 3BTK
APITOLISIBChEMBLPhase 2BTK
AT-9283ChEMBLPhase 2BTK
ATUZABRUTINIBChEMBLPhase 2BTK
BIIB-091ChEMBLPhase 2BTK
BMS-754807ChEMBLPhase 2BTK
BMS-919373ChEMBLPhase 2BTK
BMS-986142ChEMBLPhase 2BTK
BRANEBRUTINIBChEMBLPhase 2BTK
CENISERTIBChEMBLPhase 2BTK
CEP-11981ChEMBLPhase 2BTK
DANUSERTIBChEMBLPhase 2BTK
DEFOSBARASERTIBChEMBLPhase 2BTK
EDRALBRUTINIBChEMBLPhase 2BTK
ELSUBRUTINIBChEMBLPhase 2BTK
FORETINIBChEMBLPhase 2BTK
ILORASERTIBChEMBLPhase 2BTK
MILREBRUTINIBChEMBLPhase 2BTK
PELITINIBChEMBLPhase 2BTK
POSELTINIBChEMBLPhase 2BTK
R-406ChEMBLPhase 2BTK