Evobrutinib
drugOn this page
Also known as M-2951M2951Msc-2364447cMsc2364447c
Summary
Evobrutinib (CHEMBL4072833) is a phase-3 clinical-stage small molecule targeting BTK; indicated across 6 conditions including relapsing-remitting 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: 16
- Chemistry: 429.5 Da · C25H27N5O2
Identifiers
Drug identity and classification
| Field | Value |
|---|---|
| ChEMBL ID | CHEMBL4072833 |
| Name | Evobrutinib |
| Type | Small molecule |
| Max phase | 3 |
| FDA approved | no |
| PubChem CID | 71479709 |
| Molecular formula | C25H27N5O2 |
| Molecular weight | 429.5 |
| InChIKey | QUIWHXQETADMGN-UHFFFAOYSA-N |
SMILES: C=CC(=O)N1CCC(CC1)CNC2=NC=NC(=C2C3=CC=C(C=C3)OC4=CC=CC=C4)N
IUPAC name: 1-[4-[[[6-amino-5-(4-phenoxyphenyl)pyrimidin-4-yl]amino]methyl]piperidin-1-yl]prop-2-en-1-one
Also known as: Evobrutinib, M-2951, M2951, Msc-2364447c, Msc2364447c, EVOBRUTINIB, evobrutinib
Patent coverage: 343 distinct patent families (960 SureChEMBL compound mentions), from 1 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).
| Gene | Target | Action | pAffinity | Cancer dependency | UniProt |
|---|---|---|---|---|---|
| BTK | Bruton tyrosine kinase | Inhibition | 7 | 0.7% | Q06187 |
Broader ChEMBL bioactivity targets: 10 (assay-derived). Sample: Epidermal growth factor receptor, Voltage-gated inwardly rectifying potassium channel KCNH2, Tyrosine-protein kinase ITK/TSK, Receptor tyrosine-protein kinase erbB-4, Early activation antigen CD69, Platelet glycoprotein VI, Cytoplasmic tyrosine-protein kinase BMX, ADP-sugar pyrophosphatase, Tyrosine-protein kinase Tec, Tyrosine-protein kinase BTK.
Bioactivity
ChEMBL activities: 28 potent at pChembl ≥ 5 of 29 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):
| Target | pChembl | Type | Value | Unit | Activity ID |
|---|---|---|---|---|---|
| BTK | 8.74 | IC50 | 1.83 | nM | CHEMBL_ACT_24693328 |
| TEC | 8.35 | Kd | 4.5 | nM | CHEMBL_ACT_19061196 |
| BTK | 8.34 | Kd | 4.6 | nM | CHEMBL_ACT_24398655 |
| BTK | 8.34 | Kd | 4.6 | nM | CHEMBL_ACT_25838083 |
| BTK | 8.3 | IC50 | 5 | nM | CHEMBL_ACT_24398440 |
| BTK | 8.05 | IC50 | 8.9 | nM | CHEMBL_ACT_19132970 |
| BTK | 8.05 | IC50 | 8.9 | nM | CHEMBL_ACT_25030293 |
| BTK | 7.8 | Kd | 16 | nM | CHEMBL_ACT_19061184 |
| BTK | 7.77 | IC50 | 16.9 | nM | CHEMBL_ACT_25588749 |
| TEC | 7.7 | IC50 | 20 | nM | CHEMBL_ACT_25067061 |
| BTK | 7.66 | IC50 | 22 | nM | CHEMBL_ACT_25067004 |
| BMX | 7.51 | Kd | 31 | nM | CHEMBL_ACT_19061190 |
| BMX | 7.42 | IC50 | 37.9 | nM | CHEMBL_ACT_18109374 |
| TEC | 7.42 | IC50 | 37.9 | nM | CHEMBL_ACT_18109375 |
| ERBB4 | 7.42 | IC50 | 37.9 | nM | CHEMBL_ACT_18109376 |
| BTK | 7.21 | IC50 | 62 | nM | CHEMBL_ACT_19061027 |
| BTK | 7.21 | IC50 | 61 | nM | CHEMBL_ACT_19061057 |
| BTK | 7.21 | IC50 | 61 | nM | CHEMBL_ACT_19133007 |
| BTK | 6.5 | IC50 | 320 | nM | CHEMBL_ACT_19061085 |
| CD69 | 5.96 | IC50 | 1100 | nM | CHEMBL_ACT_24398497 |
| BTK | 5.93 | IC50 | 1182 | nM | CHEMBL_ACT_19061324 |
| KCNH2 | 5.51 | Ki | 3100 | nM | CHEMBL_ACT_19133043 |
| ITK | 5.43 | Kd | 3700 | nM | CHEMBL_ACT_19061202 |
| ERBB4 | 5.25 | Kd | 5600 | nM | CHEMBL_ACT_19061220 |
| EGFR | 5.24 | IC50 | 5800 | nM | CHEMBL_ACT_19132991 |
| GP6 | 5.23 | IC50 | 5840 | nM | CHEMBL_ACT_22480801 |
| EGFR | 5.15 | Kd | 7100 | nM | CHEMBL_ACT_19061208 |
| BTK | 5.07 | IC50 | 8600 | nM | CHEMBL_ACT_19133077 |
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 |
|---|---|---|---|
| relapsing-remitting multiple sclerosis | 3 | MONDO:0005314 | EFO:0003929 |
| multiple sclerosis | 3 | MONDO:0005301 | MONDO:0005301 |
| rheumatoid arthritis | 2 | MONDO:0008383 | EFO:0000685 |
| systemic lupus erythematosus | 2 | MONDO:0007915 | MONDO:0007915 |
| kidney disorder | 1 | MONDO:0005240 | EFO:0003086 |
| liver disorder | 1 | MONDO:0005154 | EFO:0001421 |
Clinical trials
Total trials: 16.
Phase distribution
| Phase | Trials |
|---|---|
| PHASE1 | 9 |
| PHASE3 | 4 |
| PHASE2 | 3 |
Top trials by phase / activity
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT04032158 | PHASE3 | TERMINATED | Study of Evobrutinib in Participants With Relapsing Multiple Sclerosis (RMS) |
| NCT04032171 | PHASE3 | TERMINATED | Study of Evobrutinib in Participants With RMS |
| NCT04338022 | PHASE3 | TERMINATED | Study of Evobrutinib in Participants With RMS (evolutionRMS 1) |
| NCT04338061 | PHASE3 | TERMINATED | Study of Evobrutinib in Participants With RMS (evolutionRMS 2) |
| NCT02784106 | PHASE2 | COMPLETED | Safety and Efficacy Study of M2951 in Participants With Rheumatoid Arthritis |
| NCT02975336 | PHASE2 | TERMINATED | A Phase II Study of M2951 in SLE |
| NCT02975349 | PHASE2 | TERMINATED | A Study of Efficacy and Safety of M2951 in Participants With Relapsing Multiple Sclerosis |
| NCT02537028 | PHASE1 | COMPLETED | MSC2364447C Phase 1b in Systemic Lupus Erythematosus |
| NCT03436394 | PHASE1 | COMPLETED | Effect of Renal Impairment on Evobrutinib Pharmacokinetics (PK) |
| NCT03725072 | PHASE1 | COMPLETED | Human Absorption, Distribution, Metabolism and Excretion (ADME) of [14C]-Evobrutinib |
| NCT03934502 | PHASE1 | COMPLETED | Effect of Meal Composition and Timing on Evobrutinib Bioavailability |
| NCT04314024 | PHASE1 | COMPLETED | Relative Bioavailability (rBA) of Evobrutinib Intended Commercial and Clinical Tablets, and Effect of Food on Intended Commercial Tablets |
| NCT04697511 | PHASE1 | COMPLETED | Drug-drug Interaction Study of Evobrutinib With Midazolam in Healthy Participants |
| NCT05064488 | PHASE1 | COMPLETED | Drug-Drug Interaction Study of Evobrutinib and Transporter Substrates |
| NCT05245396 | PHASE1 | COMPLETED | Study Comparing Pharmacokinetics of Different Formulations of Evobrutinib in Healthy Participants |
| NCT05248945 | PHASE1 | COMPLETED | DDI Study of Evobrutinib and Carbamazepine |
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 |
| FENEBRUTINIB | 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 |
Related Atlas pages
- Genes: BTK
- Diseases: relapsing-remitting multiple sclerosis, multiple sclerosis
- Drugs: Crizotinib, Ritlecitinib, Acalabrutinib, Bosutinib, Brigatinib, Ceritinib, Dasatinib, Entrectinib, Fedratinib, Futibatinib, Ibrutinib, Mitoxantrone, Neratinib, Nintedanib, Olmutinib, Osimertinib, Pirtobrutinib, Ponatinib, Sunitinib, Tirabrutinib, Vandetanib, Zanubrutinib, Abivertinib, Alisertib, Canertinib, Cediranib, Dovitinib, Entospletinib, Fenebrutinib, Lestaurtinib, Nemtabrutinib, Orelabrutinib, Poziotinib, Pyrotinib, Remibrutinib, Rilzabrutinib, Rociletinib, Saracatinib, Tesevatinib, Tolebrutinib