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Defactinib

drug
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Also known as PF-04554878Vs-6063DEFACTINIB HYDROCHLORIDEDEFACITINIBDEFACTINIB (VS-6063)PF_04554878

Summary

Defactinib (CHEMBL3137331) is a phase-3 clinical-stage small molecule targeting LATS1; indicated across 13 conditions including ovarian cancer and non-small cell lung carcinoma.

At a glance

  • Status: Max clinical phase 3 (not approved)
  • Modality: Small molecule
  • Targets: 1 (LATS1)
  • Indications: 13 conditions
  • Clinical trials: 32
  • Chemistry: 510.5 Da · C20H21F3N8O3S

Identifiers

Drug identity and classification

FieldValue
ChEMBL IDCHEMBL3137331
NameDefactinib
TypeSmall molecule
Max phase3
FDA approvedno
PubChem CID25117126
Molecular formulaC20H21F3N8O3S
Molecular weight510.5
InChIKeyFWLMVFUGMHIOAA-UHFFFAOYSA-N

SMILES: CNC(=O)C1=CC=C(C=C1)NC2=NC=C(C(=N2)NCC3=NC=CN=C3N(C)S(=O)(=O)C)C(F)(F)F

IUPAC name: N-methyl-4-[[4-[[3-[methyl(methylsulfonyl)amino]pyrazin-2-yl]methylamino]-5-(trifluoromethyl)pyrimidin-2-yl]amino]benzamide

Also known as: Defactinib, PF-04554878, Vs-6063, VS-6063, DEFACTINIB, DEFACTINIB HYDROCHLORIDE, DEFACITINIB, DEFACTINIB (VS-6063), PF_04554878, Defacitinib

Parent form; salt/anhydrous children: CHEMBL3137305

Patent coverage: 472 distinct patent families (1,229 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).

GeneTargetActionpAffinityCancer dependencyUniProt
LATS1large tumor suppressor kinase 1Inhibition5.040.1%O95835

Broader ChEMBL bioactivity targets: 53 (assay-derived). Sample: Cyclin-dependent kinase-like 5, Cyclin-dependent kinase 13, Tyrosine-protein kinase ABL1, Vascular endothelial growth factor receptor 1, Receptor-type tyrosine-protein kinase FLT3, Proto-oncogene tyrosine-protein kinase receptor Ret, D(1A) dopamine receptor, Cyclin-dependent kinase 2/cyclin A, Tyrosine-protein kinase JAK3, Aurora kinase B.

Bioactivity

ChEMBL activities: 78 potent at pChembl ≥ 5 of 84 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

TargetpChemblTypeValueUnitActivity ID
PTK29.7IC500.2nMCHEMBL_ACT_23382439
PTK2B9.7IC500.2nMCHEMBL_ACT_23382440
PTK29.7IC500.2nMCHEMBL_ACT_24954310
PTK2B9.7IC500.2nMCHEMBL_ACT_24954311
PTK29.3Kd0.5nMCHEMBL_ACT_17932597
PTK29.22IC500.6nMCHEMBL_ACT_19044507
PTK29.22IC500.6nMCHEMBL_ACT_25496033
PTK29.22IC500.6nMCHEMBL_ACT_29060138
PTK2B9.22IC500.6nMCHEMBL_ACT_29060151
PTK29.2IC500.63nMCHEMBL_ACT_24880406
PTK29Ki1nMCHEMBL_ACT_26335292
PTK28.94IC501.16nMCHEMBL_ACT_23218535
PTK28.9IC501.26nMCHEMBL_ACT_29141579
PTK28.83IC501.49nMCHEMBL_ACT_29316112
PTK28.82IC501.5nMCHEMBL_ACT_22445687
PTK28.75IC501.79nMCHEMBL_ACT_27786029
PTK28.52IC503nMCHEMBL_ACT_23382441
PTK28.52IC503nMCHEMBL_ACT_24954013
PTK28.41IC503.9nMCHEMBL_ACT_19158891
PTK28.41IC503.9nMCHEMBL_ACT_25015006
CDKL57.8Kd16nMCHEMBL_ACT_17891427
PTK2B7.62Kd24nMCHEMBL_ACT_26335276
NTRK17.58IC5026.58nMCHEMBL_ACT_23218820
ADORA37.57Ki27nMCHEMBL_ACT_23382442
ADORA37.57Ki27nMCHEMBL_ACT_24958335
JAK27.55IC5028.21nMCHEMBL_ACT_23218829
NTRK27.26IC5054.87nMCHEMBL_ACT_23218823
NTRK17.25IC5056nMCHEMBL_ACT_23382437
NTRK17.25IC5056nMCHEMBL_ACT_24958331
NTRK37.24IC5057.83nMCHEMBL_ACT_23218826

Target pathways

Aggregated over 1 target gene(s): LATS1.

Top Reactome pathways

2 total, by targets touching each:

PathwayTargetsGenes
Signal Transduction1LATS1
Signaling by Hippo1LATS1

Dominant GO biological processes

GO termTargets
G1/S transition of mitotic cell cycle1
G2/M transition of mitotic cell cycle1
sister chromatid segregation1
inner cell mass cell fate commitment1
inner cell mass cellular morphogenesis1
protein phosphorylation1
intracellular protein localization1
hormone-mediated signaling pathway1
regulation of transforming growth factor beta receptor signaling pathway1
keratinocyte differentiation1
regulation of actin filament polymerization1
regulation of intracellular estrogen receptor signaling pathway1
hippo signaling1
positive regulation of apoptotic process1
regulation of protein-containing complex assembly1

Indications & clinical

Indications

13 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
ovarian cancer3MONDO:0008170MONDO:0008170
non-small cell lung carcinoma2MONDO:0005233EFO:0003060
malignant pleural mesothelioma2MONDO:0005112EFO:0000770
exocrine pancreatic carcinoma2MONDO:0005192EFO:0002618
female reproductive system neoplasm2MONDO:0021148MONDO:0021148
thyroid gland carcinoma2MONDO:0015075EFO:0002892
pancreatic ductal adenocarcinoma2MONDO:0005184MONDO:0005184
colorectal neoplasm2MONDO:0005335MONDO:0005575
lung neoplasm2MONDO:0021117MONDO:0008903
endometrioid adenocarcinoma1MONDO:0005026EFO:0000466
neoplasm1MONDO:0005070MONDO:0004992
melanoma1MONDO:0005105EFO:0000756
glioblastoma0MONDO:0018177EFO:0000519

Clinical trials

Total trials: 32.

Phase distribution

PhaseTrials
PHASE215
PHASE110
PHASE1/PHASE25
PHASE31
EARLY_PHASE11

Top trials by phase / activity

NCTPhaseStatusTitle
NCT06072781PHASE3RECRUITINGA Study of Avutometinib (VS-6766) + Defactinib (VS-6063) in Recurrent Low-Grade Serous Ovarian Cancer
NCT02465060PHASE2ACTIVE_NOT_RECRUITINGTargeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma (The MATCH Screening Trial)
NCT03287271PHASE1/PHASE2RECRUITINGROCKIF Trial: Re-sensitization of Carboplatin-resistant Ovarian Cancer With Kinase Inhibition of FAK
NCT04331041PHASE2ACTIVE_NOT_RECRUITINGStereotactic Body Radiotherapy and Focal Adhesion Kinase Inhibitor in Advanced Pancreas Adenocarcinoma
NCT04439331PHASE2ACTIVE_NOT_RECRUITINGTesting VS-6063 (Defactinib) as a Potential Targeted Treatment in Cancers With NF2 Genetic Changes (MATCH-Subprotocol U)
NCT05074810PHASE1/PHASE2ACTIVE_NOT_RECRUITINGPhase 1/2 Study of Avutometinib (VS-6766) + Sotorasib With or Without Defactinib in KRAS G12C NSCLC Patients
NCT05787561PHASE2RECRUITINGA Study of Avutometinib (VS-6766) and Defactinib in People With Mesonephric Gynecologic Cancer
NCT06007924PHASE2RECRUITINGA Study of Avutometinib and Defactinib in People With Thyroid Cancer
NCT06194929PHASE1/PHASE2RECRUITINGDefactinib and Avutometinib, With or Without Encorafenib, for the Treatment of Patients With Brain Metastases From Cutaneous Melanoma
NCT06369259PHASE2RECRUITINGOpen-label Phase 2 Study of Avutometinib (RAF/MEK Clamp) in Combination With Defactinib (FAK Inhibitor) and Cetuximab in Patients With Unresectable, Anti-EGFR-Refractory Advanced Colorectal Cancer
NCT06394804PHASE2RECRUITINGA Study of Avutometinib, Defactinib, and Letrozole in People With Low-Grade Serous Ovarian Cancer
NCT06487221PHASE2RECRUITINGAvutometinib and Defactinib in Diffuse Gastric Cancer
NCT06495125PHASE2RECRUITINGDefactinib, Avutometinib and Nivolumab for the Treatment of Anti-PD1 Refractory LKB1-Mutant Advanced Non-Small Cell Lung Cancer
NCT06630260PHASE1/PHASE2RECRUITING5G-RUBY: Avutometinib and Defactinib in Malignant Brain Tumours
NCT07126158PHASE2RECRUITINGStereotactic Body Radiotherapy Plus FAK and RAF/MEK Inhibition in Advanced Pancreatic Adenocarcinoma
NCT01870609PHASE2TERMINATEDPlacebo Controlled Study of VS-6063 in Subjects With Malignant Pleural Mesothelioma
NCT01951690PHASE2COMPLETEDPhase II Study of VS-6063 in Patients With KRAS Mutant Non-Small Cell Lung Cancer
NCT02004028PHASE2TERMINATEDWindow of Opportunity Study of VS-6063 (Defactinib) in Surgical Resectable Malignant Pleural Mesothelioma Participants
NCT02758587PHASE1/PHASE2UNKNOWNStudy of FAK (Defactinib) and PD-1 (Pembrolizumab) Inhibition in Advanced Solid Malignancies (FAK-PD1)
NCT03727880PHASE2COMPLETEDStudy of Pembrolizumab With or Without Defactinib Following Chemotherapy as a Neoadjuvant and Adjuvant Treatment for Resectable Pancreatic Ductal Adenocarcinoma
NCT04720417PHASE2TERMINATEDDefactinib and VS-6766 for the Treatment of Patients With Metastatic Uveal Melanoma
NCT03875820PHASE1ACTIVE_NOT_RECRUITINGPhase I Trial of Defactinib and VS-6766.
NCT05636514PHASE1RECRUITINGCombined Evaluation of Epigenetic and Sensitising Therapy in AML and MDS
NCT07318324PHASE1NOT_YET_RECRUITINGPhase Ib Study of Avutometinib, Defactinib, and Everolimus in RAS Pathway Mutant Endometrial Cancer
NCT00787033PHASE1COMPLETEDA Study Of PF-04554878 In Patients With Advanced Non-Hematologic Malignancies
NCT01778803PHASE1COMPLETEDPhase I/Ib Study of Paclitaxel in Combination With VS-6063 in Patients With Advanced Ovarian Cancer
NCT01943292PHASE1COMPLETEDPhase I Dose Escalation Study of VS-6063 in Japanese Subjects With Non-Hematologic Malignancies
NCT02372227PHASE1TERMINATEDA Phase 1 Dose Escalation Study of VS-5584 Administered in Combination With VS-6063, in Subjects With Relapsed Malignant Mesothelioma
NCT02546531PHASE1COMPLETEDDefactinib Combined With Pembrolizumab and Gemcitabine in Patients With Advanced Cancer
NCT02913716PHASE1COMPLETEDA Phase I, Open-label Study of Absorption, Metabolism, and Excretion of Defactinib (VS-6063) in Healthy Male Subjects
NCT04201145PHASE1WITHDRAWNPembrolizumab + Defactinib In Pleural Mesothelioma
NCT05798507EARLY_PHASE1ACTIVE_NOT_RECRUITINGIdentification of Treatment Concentrations of Defactinib or VS-6766 for the Treatment of Patients With Glioblastoma

Clinical evidence (CIViC)

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

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.

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

MoleculeSourceStatusShared targets
CAPIVASERTIBChEMBL + PubChemPhase 4 (approved)LATS1
FOSTAMATINIBChEMBL + PubChemPhase 4 (approved)LATS1
GILTERITINIBChEMBL + PubChemPhase 4 (approved)LATS1
IBRUTINIBChEMBL + PubChemPhase 4 (approved)LATS1
MIDOSTAURINChEMBL + PubChemPhase 4 (approved)LATS1
SUNITINIBChEMBL + PubChemPhase 4 (approved)LATS1
NINTEDANIBChEMBLPhase 4 (approved)LATS1
CRENOLANIBChEMBLPhase 3LATS1
DOVITINIBChEMBLPhase 3LATS1
FASUDILChEMBLPhase 3LATS1
LESTAURTINIBChEMBLPhase 3LATS1
LINIFANIBChEMBLPhase 3LATS1
LINSITINIBChEMBLPhase 3LATS1
ORANTINIBChEMBLPhase 3LATS1
RUBOXISTAURINChEMBLPhase 3LATS1
AT-9283ChEMBLPhase 2LATS1
MILCICLIBChEMBLPhase 2LATS1
SCH-900776ChEMBLPhase 2LATS1
SU-014813ChEMBLPhase 2LATS1
TG100-115ChEMBLPhase 2LATS1
TOZASERTIBChEMBLPhase 2LATS1
UPROSERTIBChEMBLPhase 2LATS1
AbemaciclibPubChemApprovedLATS1
AcalabrutinibPubChemApprovedLATS1
AfatinibPubChemApprovedLATS1
AlectinibPubChemApprovedLATS1
AlpelisibPubChemApprovedLATS1
AxitinibPubChemApprovedLATS1
BaricitinibPubChemApprovedLATS1
BinimetinibPubChemApprovedLATS1
BosutinibPubChemApprovedLATS1
CabozantinibPubChemApprovedLATS1
CapmatinibPubChemApprovedLATS1
CeritinibPubChemApprovedLATS1
CobimetinibPubChemApprovedLATS1
CrizotinibPubChemApprovedLATS1
DabrafenibPubChemApprovedLATS1
dacomitinibPubChemApprovedLATS1
DuvelisibPubChemApprovedLATS1
EncorafenibPubChemApprovedLATS1
EntrectinibPubChemApprovedLATS1
ErlotinibPubChemApprovedLATS1
EverolimusPubChemApprovedLATS1
FedratinibPubChemApprovedLATS1
GefitinibPubChemApprovedLATS1
IdelalisibPubChemApprovedLATS1
ImatinibPubChemApprovedLATS1
LapatinibPubChemApprovedLATS1
LenvatinibPubChemApprovedLATS1
mirdametinibPubChemApprovedLATS1
MomelotinibPubChemApprovedLATS1
NeratinibPubChemApprovedLATS1
NilotinibPubChemApprovedLATS1
OsimertinibPubChemApprovedLATS1
PacritinibPubChemApprovedLATS1
PalbociclibPubChemApprovedLATS1
PazopanibPubChemApprovedLATS1
PexidartinibPubChemApprovedLATS1
PonatinibPubChemApprovedLATS1
QuizartinibPubChemApprovedLATS1

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