Abivertinib

drug
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Also known as A610AC-0010Ac0010ACEA100610AvitinibEX-ACEA0010

Summary

Abivertinib (CHEMBL4297865) is a phase-3 clinical-stage small molecule targeting EGFR, BTK, and JAK3; indicated across 3 conditions including non-small cell lung carcinoma and severe acute respiratory syndrome.

At a glance

  • Status: Max clinical phase 3 (not approved)
  • Modality: Small molecule
  • Targets: 3 (EGFR, BTK, JAK3)
  • Indications: 3 conditions
  • Clinical trials: 9
  • Chemistry: 487.5 Da · C26H26FN7O2

Identifiers

Drug identity and classification

FieldValue
ChEMBL IDCHEMBL4297865
NameAbivertinib
TypeSmall molecule
Max phase3
FDA approvedno
PubChem CID72734520
Molecular formulaC26H26FN7O2
Molecular weight487.5
InChIKeyUOFYSRZSLXWIQB-UHFFFAOYSA-N

SMILES: CN1CCN(CC1)C2=C(C=C(C=C2)NC3=NC4=C(C=CN4)C(=N3)OC5=CC=CC(=C5)NC(=O)C=C)F

IUPAC name: N-[3-[[2-[3-fluoro-4-(4-methylpiperazin-1-yl)anilino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]oxy]phenyl]prop-2-enamide

Also known as: A610, Abivertinib, AC-0010, Ac0010, AC0010, ACEA100610, Avitinib, EX-ACEA0010, ABIVERTINIB

Parent form; salt/anhydrous children: CHEMBL4297866, CHEMBL5307684

Patent coverage: 462 distinct patent families (1,194 SureChEMBL compound mentions), from 4 matched compound structure(s). One matched structure accounts for 1,106 (93%) 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
EGFRepidermal growth factor receptorInhibition8.1117.5%P00533
BTKBruton tyrosine kinaseInhibition9.40.7%Q06187
JAK3Janus kinase 3Inhibition10.050.6%P52333

Broader ChEMBL bioactivity targets: 6 (assay-derived). Sample: Leucine-rich repeat serine/threonine-protein kinase 2, Epidermal growth factor receptor, Tyrosine-protein kinase JAK3, Tyrosine-protein kinase JAK1, Tyrosine-protein kinase JAK2, Tyrosine-protein kinase BTK.

Bioactivity

ChEMBL activities: 12 potent at pChembl ≥ 5 of 12 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

TargetpChemblTypeValueUnitActivity ID
JAK310.04IC500.09nMCHEMBL_ACT_26980111
EGFR9.77IC500.17nMCHEMBL_ACT_23243141
BTK9.4IC500.4nMCHEMBL_ACT_26980108
EGFR9.24IC500.58nMCHEMBL_ACT_23243147
EGFR8.74IC501.8nMCHEMBL_ACT_23243135
EGFR8.68IC502.1nMCHEMBL_ACT_23243138
EGFR7.68IC5021nMCHEMBL_ACT_23243132
LRRK26.75IC50177nMCHEMBL_ACT_25654353
EGFR6.55IC50279nMCHEMBL_ACT_23243150
LRRK26.39IC50410.3nMCHEMBL_ACT_25654300
JAK26.3IC50501nMCHEMBL_ACT_26980114
JAK15.49IC503270nMCHEMBL_ACT_26980117

Target pathways

Aggregated over 3 target gene(s): EGFR, BTK, JAK3.

Top Reactome pathways

98 total, by targets touching each:

PathwayTargetsGenes
Signal Transduction2BTK, JAK3
Disease2BTK, JAK3
Immune System2BTK, JAK3
Infectious disease2BTK, JAK3
RAF/MAP kinase cascade2EGFR, JAK3
Potential therapeutics for SARS2BTK, JAK3
SARS-CoV Infections2BTK, JAK3
Viral Infection Pathways2BTK, JAK3
Signaling by ERBB21EGFR
Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants1EGFR
Signaling by ERBB41EGFR
ER-Phagosome pathway1BTK
Antigen processing-Cross presentation1BTK
SHC1 events in ERBB2 signaling1EGFR
PLCG1 events in ERBB2 signaling1EGFR
PIP3 activates AKT signaling1EGFR
Interleukin-7 signaling1JAK3
Cytokine Signaling in Immune system1JAK3
Adaptive Immune System1BTK
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
Toll-like Receptor Cascades1BTK
Signaling by EGFR1EGFR
GRB2 events in EGFR signaling1EGFR
GAB1 signalosome1EGFR
SHC1 events in EGFR signaling1EGFR
Toll Like Receptor 2 (TLR2) Cascade1BTK

Dominant GO biological processes

GO termTargets
protein phosphorylation3
adaptive immune response2
negative regulation of interleukin-10 production2
intracellular signal transduction2
innate immune response2
immune system process2
cell morphogenesis1
ossification1
embryonic placenta development1
positive regulation of protein phosphorylation1
hair follicle development1
ubiquitin-dependent protein catabolic process1
signal transduction1
cell surface receptor signaling pathway1
epidermal growth factor receptor signaling pathway1

Indications & clinical

Indications

3 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
non-small cell lung carcinoma3MONDO:0005233EFO:0003060
severe acute respiratory syndrome2MONDO:0005091MONDO:0100096

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

Clinical trials

Total trials: 9.

Phase distribution

PhaseTrials
PHASE24
PHASE1/PHASE22
PHASE12
PHASE31

Top trials by phase / activity

NCTPhaseStatusTitle
NCT03058094PHASE3WITHDRAWNA Study Comparing AC0010 and Chemotherapy in Patients With Advanced NSCLC Who Have Progressed Following Prior EGFR TKI
NCT02274337PHASE1/PHASE2UNKNOWNSafety, Tolerability, Pharmacokinetics and Anti-tumour Activity of AC0010 in Advanced Non Small Cell Lung Cancer
NCT02330367PHASE1/PHASE2UNKNOWNSafety, Pharmacokinetic and Preliminary Efficacy Study of AC0010 in Patients With EGFR T790M Positive NSCLC
NCT03300115PHASE2UNKNOWNClinical Trial of the Efficacy and Safety of AC0010 in the Treatment of EGFR T790M Patients With Advanded NSCLC
NCT03574402PHASE2UNKNOWNPhase II Umbrella Study Directed by Next Generation Sequencing
NCT04440007PHASE2COMPLETEDStudy of the Efficacy and Safety of STI-5656 (Abivertinib Maleate) in Subjects Hospitalized With COVID-19
NCT05361915PHASE2SUSPENDEDStudy to Assess Abivertinib in Combination With Abiraterone in Metastatic Castration Resistant Prostate Cancer
NCT03001609PHASE1COMPLETEDStudy to Investigate the Absorption, Metabolism and Excretion of [14C] AC0010 in Patients With Advanced NSCLC
NCT03053219PHASE1COMPLETEDPreliminary Evaluation of Safety and Efficacy by [14C] AC0010 Trail and Subsequent AC0010 Treatment

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.

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

MoleculeSourceStatusShared targets
AFATINIBChEMBL + PubChemPhase 4 (approved)BTK, EGFR, JAK3
CRIZOTINIBChEMBL + PubChemPhase 4 (approved)BTK, EGFR, JAK3
DACOMITINIBChEMBL + PubChemPhase 4 (approved)BTK, EGFR, JAK3
MOBOCERTINIBChEMBL + PubChemPhase 4 (approved)BTK, EGFR, JAK3
PazopanibChEMBL + PubChemPhase 4 (approved)BTK, EGFR, JAK3
SELUMETINIBChEMBL + PubChemPhase 4 (approved)BTK, EGFR, JAK3
ACALABRUTINIBChEMBLPhase 4 (approved)BTK, EGFR, JAK3
BOSUTINIBChEMBLPhase 4 (approved)BTK, EGFR, JAK3
CERITINIBChEMBLPhase 4 (approved)BTK, EGFR, JAK3
DASATINIBChEMBLPhase 4 (approved)BTK, EGFR, JAK3
FEDRATINIBChEMBLPhase 4 (approved)BTK, EGFR, JAK3
IBRUTINIBChEMBLPhase 4 (approved)BTK, EGFR, JAK3
NERATINIBChEMBLPhase 4 (approved)BTK, EGFR, JAK3
OSIMERTINIBChEMBLPhase 4 (approved)BTK, EGFR, JAK3
SUNITINIBChEMBLPhase 4 (approved)BTK, EGFR, JAK3
ZANUBRUTINIBChEMBLPhase 4 (approved)BTK, EGFR, JAK3
CANERTINIBChEMBLPhase 3BTK, EGFR, JAK3
DOVITINIBChEMBLPhase 3BTK, EGFR, JAK3
LESTAURTINIBChEMBLPhase 3BTK, EGFR, JAK3
REMIBRUTINIBChEMBLPhase 3BTK, EGFR, JAK3
ROCILETINIBChEMBLPhase 3BTK, EGFR, JAK3
BRANEBRUTINIBChEMBLPhase 2BTK, EGFR, JAK3
CENISERTIBChEMBLPhase 2BTK, EGFR, JAK3
PELITINIBChEMBLPhase 2BTK, EGFR, JAK3
R-406ChEMBLPhase 2BTK, EGFR, JAK3
SPEBRUTINIBChEMBLPhase 2BTK, EGFR, JAK3
SU-014813ChEMBLPhase 2BTK, EGFR, JAK3
TOZASERTIBChEMBLPhase 2BTK, EGFR, JAK3
GEFITINIBChEMBL + PubChemPhase 4 (approved)EGFR, JAK3
RITLECITINIBChEMBL + PubChemPhase 4 (approved)BTK, JAK3
AXITINIBChEMBLPhase 4 (approved)EGFR, JAK3
BRIGATINIBChEMBLPhase 4 (approved)BTK, EGFR
ENTRECTINIBChEMBLPhase 4 (approved)BTK, JAK3
ERLOTINIBChEMBLPhase 4 (approved)EGFR, JAK3
MIDOSTAURINChEMBLPhase 4 (approved)EGFR, JAK3
MITOXANTRONEChEMBLPhase 4 (approved)BTK, EGFR
NINTEDANIBChEMBLPhase 4 (approved)BTK, JAK3
OLMUTINIBChEMBLPhase 4 (approved)BTK, EGFR
PONATINIBChEMBLPhase 4 (approved)BTK, EGFR
SORAFENIBChEMBLPhase 4 (approved)EGFR, JAK3
VANDETANIBChEMBLPhase 4 (approved)BTK, EGFR
ALISERTIBChEMBLPhase 3BTK, EGFR
ALVOCIDIBChEMBLPhase 3EGFR, JAK3
CEDIRANIBChEMBLPhase 3BTK, EGFR
EVOBRUTINIBChEMBLPhase 3BTK, EGFR
ORELABRUTINIBChEMBLPhase 3BTK, EGFR
POZIOTINIBChEMBLPhase 3BTK, EGFR
PYROTINIBChEMBLPhase 3BTK, EGFR
RUBOXISTAURINChEMBLPhase 3EGFR, JAK3
SARACATINIBChEMBLPhase 3BTK, EGFR
TESEVATINIBChEMBLPhase 3BTK, EGFR
TOLEBRUTINIBChEMBLPhase 3BTK, EGFR
APITOLISIBChEMBLPhase 2BTK, EGFR
AT-9283ChEMBLPhase 2BTK, JAK3
ATUZABRUTINIBChEMBLPhase 2BTK, EGFR
BMS-919373ChEMBLPhase 2BTK, JAK3
DEFOSBARASERTIBChEMBLPhase 2BTK, EGFR
FORETINIBChEMBLPhase 2BTK, EGFR
ILORASERTIBChEMBLPhase 2BTK, EGFR
POSELTINIBChEMBLPhase 2BTK, JAK3