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Tovorafenib

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Also known as Biib-024BIIB024DAY-101DAY101Mln-2480Mln2480OjemdaTak 580Tak-580SID174006384

Summary

Tovorafenib (CHEMBL3348923) is an approved small-molecule antineoplastic agent targeting BRAF; indicated across 14 conditions including glioma and craniopharyngioma; with CIViC clinical evidence for 2 variant-indication associations (e.g. BRAF V600 OR v::BRAF Fusion in childhood low-grade glioma).

At a glance

  • Status: Approved (max clinical phase 4)
  • Modality: Small molecule
  • Targets: 1 (BRAF)
  • Indications: 14 conditions
  • Clinical trials: 15
  • Precision-oncology evidence (CIViC): 2 variant–indication associations
  • Chemistry: 506.3 Da · C17H12Cl2F3N7O2S

Identifiers

Drug identity and classification

FieldValue
ChEMBL IDCHEMBL3348923
NameTovorafenib
TypeSmall molecule
Max phase4
FDA approvedyes
PubChem CID25161177
ChEBICHEBI:167672
Molecular formulaC17H12Cl2F3N7O2S
Molecular weight506.3
InChIKeyVWMJHAFYPMOMGF-ZCFIWIBFSA-N

SMILES: C[C@H](C1=NC=C(S1)C(=O)NC2=NC=C(C(=C2)C(F)(F)F)Cl)NC(=O)C3=C(C(=NC=N3)N)Cl

IUPAC name: 2-[(1R)-1-[(6-amino-5-chloropyrimidine-4-carbonyl)amino]ethyl]-N-[5-chloro-4-(trifluoromethyl)-2-pyridinyl]-1,3-thiazole-5-carboxamide

ChEBI definition: A 1,3-thiazolecarboxamide that is 2-[(1R)-1-aminoethyl]-1,3-thiazole-5-carboxylic acid in which the carboxy group undergoes formal condensation with the amino group of 5-chloro-4-(trifluoromethyl)pyridin-2-amine and in which the amino group undergoes formal condensation with the carboxy group of 6-amino-5-chloropyrimidine-4-carboxylic acid. It is a pan-RAF kinase inhibitor which is currently in clinical development for the treatment of radiographically recurrent or progressive low-grade glioma in children and young adults.

Pharmacological roles (ChEBI): antineoplastic agent, apoptosis inducer, B-Raf inhibitor.

Also known as: Biib-024, BIIB-024, BIIB024, DAY-101, DAY101, Mln-2480, MLN-2480, Mln2480, Ojemda, Tak 580, Tak-580, TAK-580

Patent coverage: 315 distinct patent families (834 SureChEMBL compound mentions), from 3 matched compound structure(s). One matched structure accounts for 740 (89%) 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).

GeneTargetActionpAffinityCancer dependencyUniProt
BRAFB-Raf proto-oncogene, serine/threonine kinaseInhibition5.728.6%P15056

Broader ChEMBL bioactivity targets: 25 (assay-derived). Sample: Receptor-interacting serine/threonine-protein kinase 3, Tyrosine-protein kinase ABL1, RAF proto-oncogene serine/threonine-protein kinase, Platelet-derived growth factor receptor beta, Ephrin type-A receptor 2, Dual specificity tyrosine-phosphorylation-regulated kinase 1A, Myosin light chain kinase, smooth muscle, Mitogen-activated protein kinase 14, Dual specificity mitogen-activated protein kinase kinase 4, LIM domain kinase 1.

Bioactivity

ChEMBL activities: 27 potent at pChembl ≥ 5 of 28 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

TargetpChemblTypeValueUnitActivity ID
DDR17.2Kd63nMCHEMBL_ACT_17896168
RAF17.03IC5094nMCHEMBL_ACT_26027102
BRAF7.03IC5094.2nMCHEMBL_ACT_26027116
ABL27Kd99nMCHEMBL_ACT_17878719
MAP2K46.84Kd146nMCHEMBL_ACT_17911060
FRK6.76Kd172nMCHEMBL_ACT_17903825
DDR26.64Kd227nMCHEMBL_ACT_17896428
WEE16.6Kd252nMCHEMBL_ACT_17947914
BCR6.53Kd296nMCHEMBL_ACT_17884741
MAPK146.45Kd358nMCHEMBL_ACT_17915379
MAP3K206.35Kd450nMCHEMBL_ACT_17948596
ABL16.3Kd498nMCHEMBL_ACT_17878461
RAF16.3IC50495nMCHEMBL_ACT_26027125
BRAF6.2IC50633nMCHEMBL_ACT_26027107
MAPK116.17Kd684nMCHEMBL_ACT_17915107
EPHA26.09Kd807nMCHEMBL_ACT_17899527
CLK16.03Kd942nMCHEMBL_ACT_17892304
LIMK15.99Kd1021nMCHEMBL_ACT_17909719
EPHA15.97Kd1067nMCHEMBL_ACT_17899268
TGFBR25.79Kd1641nMCHEMBL_ACT_17944942
RIPK35.75Kd1800nMCHEMBL_ACT_17935571
MAP3K15.68Kd2090nMCHEMBL_ACT_17911666
DYRK1A5.49Kd3218nMCHEMBL_ACT_17898214
EPHB65.48Kd3344nMCHEMBL_ACT_17901243
BRAF5.42Kd3772nMCHEMBL_ACT_17885959
MYLK5.36Kd4406nMCHEMBL_ACT_17919928
EPHB45.03Kd9434nMCHEMBL_ACT_17900996

Target pathways

Aggregated over 1 target gene(s): BRAF.

Top Reactome pathways

39 total, by targets touching each:

PathwayTargetsGenes
Spry regulation of FGF signaling1BRAF
Signal Transduction1BRAF
Disease1BRAF
Signaling by NTRKs1BRAF
Prolonged ERK activation events1BRAF
Frs2-mediated activation1BRAF
ARMS-mediated activation1BRAF
Signaling by NTRK1 (TRKA)1BRAF
Signalling to ERKs1BRAF
Signalling to p38 via RIT and RIN1BRAF
Signaling by FGFR1BRAF
Negative regulation of FGFR1 signaling1BRAF
Negative regulation of FGFR2 signaling1BRAF
Negative regulation of FGFR3 signaling1BRAF
Negative regulation of FGFR4 signaling1BRAF
Signaling by FGFR11BRAF
Signaling by FGFR21BRAF
Signaling by FGFR31BRAF
Signaling by FGFR41BRAF
Diseases of signal transduction by growth factor receptors and second messengers1BRAF
RAF activation1BRAF
RAF/MAP kinase cascade1BRAF
MAP2K and MAPK activation1BRAF
Negative feedback regulation of MAPK pathway1BRAF
Negative regulation of MAPK pathway1BRAF
MAPK family signaling cascades1BRAF
MAPK1/MAPK3 signaling1BRAF
Signaling by moderate kinase activity BRAF mutants1BRAF
Signaling by high-kinase activity BRAF mutants1BRAF
Signaling by RAS mutants1BRAF

Dominant GO biological processes

GO termTargets
MAPK cascade1
myeloid progenitor cell differentiation1
protein phosphorylation1
epidermal growth factor receptor signaling pathway1
visual learning1
animal organ morphogenesis1
positive regulation of gene expression1
negative regulation of fibroblast migration1
positive regulation of D-glucose transmembrane transport1
synaptic vesicle exocytosis1
thyroid gland development1
T cell differentiation in thymus1
positive regulation of peptidyl-serine phosphorylation1
substrate adhesion-dependent cell spreading1
somatic stem cell population maintenance1

Indications & clinical

Indications

14 indications (1 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
glioma4MONDO:0021042MONDO:0021637
craniopharyngioma2MONDO:0018907EFO:1000209
Langerhans cell histiocytosis2MONDO:0018310EFO:1000318
neoplasm2MONDO:0005070EFO:0000616
metastatic melanoma1MONDO:0005191EFO:0002617
melanoma1MONDO:0005105EFO:0000756
thyroid gland papillary carcinoma1MONDO:0005075EFO:0000641
exocrine pancreatic carcinoma1MONDO:0005192EFO:0002618
non-small cell lung carcinoma1MONDO:0005233EFO:0003060
astrocytoma (excluding glioblastoma)1MONDO:0019781MONDO:0016691
adenocarcinoma1MONDO:0004970EFO:0000228
colorectal neoplasm1MONDO:0005335MONDO:0005575

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

Clinical trials

Total trials: 15.

Phase distribution

PhaseTrials
PHASE16
PHASE25
PHASE31
PHASE1/PHASE21
EARLY_PHASE11
Not specified1

Top trials by phase / activity

NCTPhaseStatusTitle
NCT05566795PHASE3ACTIVE_NOT_RECRUITINGDAY101 vs. Standard of Care Chemotherapy in Pediatric Participants With Low-Grade Glioma Requiring First-Line Systemic Therapy (LOGGIC/FIREFLY-2)
NCT04775485PHASE2RECRUITINGA Study to Evaluate Tovorafenib in Pediatric and Young Adult Participants With Relapsed or Progressive Low-Grade Glioma and Advance Solid Tumors
NCT05465174PHASE2RECRUITINGTovorafenib for Treatment of Craniopharyngioma in Children and Young Adults
NCT05828069PHASE2RECRUITINGA Study With Tovorafenib (DAY101) as a Treatment Option for Progressive, Relapsed, or Refractory Langerhans Cell Histiocytosis
NCT06965114PHASE1/PHASE2RECRUITINGTesting the Combination of Anti-cancer Drugs, Tovorafenib Plus Rituximab, in Patients With Hairy Cell Leukemia
NCT07206849PHASE2NOT_YET_RECRUITINGStudy of Tovorafenib in High-Grade Glioma and Diffuse Intrinsic Pontine Glioma (DIPG)
NCT04985604PHASE2TERMINATEDTovorafenib (DAY101) Monotherapy for Patients With Melanoma and Other Solid Tumors
NCT07441707PHASE1RECRUITINGA Study to Assess a Medicine Called Tovorafenib in Japanese Children and Young Adults With Brain Tumours
NCT01425008PHASE1COMPLETEDStudy of MLN2480 in Participants With Relapsed or Refractory Solid Tumors Followed by a Dose Expansion in Participants With Metastatic Melanoma
NCT02327169PHASE1COMPLETEDA Study MLN2480 in Combination With MLN0128 or Alisertib, or Paclitaxel, or Cetuximab, or Irinotecan in Adult Participants With Advanced Nonhematologic Malignancies
NCT02723006PHASE1TERMINATEDStudy to Evaluate the Safety, Tolerability, and Pharmacodynamics of Investigational Treatments in Combination With Standard of Care Immune Checkpoint Inhibitors in Participants With Advanced Melanoma
NCT03429803PHASE1COMPLETEDDAY101 In Gliomas and Other Tumors
NCT07121829PHASE1TERMINATEDTovorafenib (DAY101) or in Combination With Pimasertib for Participants With Melanoma and Other Solid Tumors
NCT06381570EARLY_PHASE1RECRUITINGPilot Study of Vinblastine and Tovorafenib in Pediatric Patients With Recurrent/Progressive RAF Altered Low Grade Gliomas
NCT05760586Not specifiedAPPROVED_FOR_MARKETINGExpanded Access Program (EAP) for Tovorafenib (DAY101) in RAF-Altered, Relapsed or Refractory Low-Grade Glioma

Clinical evidence (CIViC)

Variant × indication × effect (2 predictive associations from 2 curated evidence items):

VariantIndicationEffectTherapyLevelCIViC
BRAF V600 OR v::BRAF FusionChildhood Low-grade GliomaSensitivity/ResponseTovorafenibCIViC AEID12028
BRAF V600E OR KIAA1549::BRAF FusionChildhood Low-grade GliomaSensitivity/ResponseTovorafenibCIViC AEID12016

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline or drug-level clinical/variant annotations in PharmGKB for this molecule.

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.

47 molecules share ≥1 primary target. Top 47 by shared-target count:

MoleculeSourceStatusShared targets
GEFITINIBChEMBL + PubChemPhase 4 (approved)BRAF
PAZOPANIBChEMBL + PubChemPhase 4 (approved)BRAF
REGORAFENIBChEMBL + PubChemPhase 4 (approved)BRAF
ABEMACICLIBChEMBLPhase 4 (approved)BRAF
COBIMETINIBChEMBLPhase 4 (approved)BRAF
DABRAFENIBChEMBLPhase 4 (approved)BRAF
DASATINIBChEMBLPhase 4 (approved)BRAF
ENCORAFENIBChEMBLPhase 4 (approved)BRAF
ERLOTINIBChEMBLPhase 4 (approved)BRAF
FEDRATINIBChEMBLPhase 4 (approved)BRAF
IMATINIBChEMBLPhase 4 (approved)BRAF
INFIGRATINIBChEMBLPhase 4 (approved)BRAF
NILOTINIBChEMBLPhase 4 (approved)BRAF
PONATINIBChEMBLPhase 4 (approved)BRAF
RUXOLITINIBChEMBLPhase 4 (approved)BRAF
SORAFENIBChEMBLPhase 4 (approved)BRAF
VEMURAFENIBChEMBLPhase 4 (approved)BRAF
AVUTOMETINIBChEMBLPhase 3BRAF
MASITINIBChEMBLPhase 3BRAF
MOTESANIBChEMBLPhase 3BRAF
NAPORAFENIBChEMBLPhase 3BRAF
QUERCETINChEMBLPhase 3BRAF
BAFETINIBChEMBLPhase 2BRAF
BELVARAFENIBChEMBLPhase 2BRAF
BRIMARAFENIBChEMBLPhase 2BRAF
CEP-32496ChEMBLPhase 2BRAF
DORAMAPIMODChEMBLPhase 2BRAF
ELLAGIC ACIDChEMBLPhase 2BRAF
EXARAFENIBChEMBLPhase 2BRAF
FORETINIBChEMBLPhase 2BRAF
LIFIRAFENIBChEMBLPhase 2BRAF
MIRDAMETINIBChEMBLPhase 2BRAF
PEXMETINIBChEMBLPhase 2BRAF
R-406ChEMBLPhase 2BRAF
RAF-265ChEMBLPhase 2BRAF
REBASTINIBChEMBLPhase 2BRAF
TG100-115ChEMBLPhase 2BRAF
TINLORAFENIBChEMBLPhase 2BRAF
XL-281ChEMBLPhase 2BRAF
AfatinibPubChemApprovedBRAF
BinimetinibPubChemApprovedBRAF
CrizotinibPubChemApprovedBRAF
dacomitinibPubChemApprovedBRAF
FostamatinibPubChemApprovedBRAF
IdelalisibPubChemApprovedBRAF
SelumetinibPubChemApprovedBRAF
TrametinibPubChemApprovedBRAF

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.2
BioBTree
v2.0.2

Sources 30

This page pulls from 30 datasets indexed by BioBTree:

chebichembl_activitychembl_moleculechembl_targetcivic_evidenceclingen_dosageclinical_trialsdepmapefoensemblentrezgogoparentgtopdbgtopdb_interactiongtopdb_ligandhgncmeshmondomsigdbpatent_compoundpharmgkbpharmgkb_guidelinepubchempubchem_activityreactomereactomeparentrefseqtranscriptuniprot