Dacomitinib Anhydrous

Summary

Dacomitinib Anhydrous (CHEMBL2110732) is an approved small-molecule epidermal growth factor receptor antagonist targeting EGFR, ERBB4, and ERBB2; indicated across 16 conditions including non-small cell lung carcinoma and lung neoplasm.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• Targets: 3 (EGFR, ERBB4, ERBB2)
• Indications: 16 conditions
• Clinical trials: 53
• Chemistry: 469.9 Da · C24H25ClFN5O2

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL2110732
Name	Dacomitinib Anhydrous
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	11511120
ChEBI	CHEBI:132268
Molecular formula	C24H25ClFN5O2
Molecular weight	469.9
InChIKey	LVXJQMNHJWSHET-AATRIKPKSA-N

SMILES: COC1=C(C=C2C(=C1)N=CN=C2NC3=CC(=C(C=C3)F)Cl)NC(=O)/C=C/CN4CCCCC4

IUPAC name: (E)-N-[4-(3-chloro-4-fluoroanilino)-7-methoxyquinazolin-6-yl]-4-piperidin-1-ylbut-2-enamide

ChEBI definition: A member of the class of quinazolines that is 7-methoxyquinazoline-4,6-diamine in which the amino group at position 4 is substituted by a 3-chloro-4-fluorophenyl group and the amino group at position 6 is substituted by an (E)-4-(piperidin-1-yl)but-2-enoyl group.

Pharmacological roles (ChEBI): epidermal growth factor receptor antagonist, antineoplastic agent.

Also known as: Dacomitinib anhydrous, Pf-00299804, Dacomitinib, DACOMITINIB ANHYDROUS, DACOMITINIB (PF299804, PF-00299804), DACOMITINIB, Dacomitinib (PF299804; PF-00299804), PF-299804, Dacomitinib; Vizimpro, dacomitinib, PF-00299804

Parent form; salt/anhydrous children: CHEMBL2105719

Patent coverage: 2,905 distinct patent families (6,578 SureChEMBL compound mentions), from 3 matched compound structure(s). One matched structure accounts for 5,167 (79%) 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).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
EGFR	epidermal growth factor receptor	Inhibition	8.22	17.5%	P00533
ERBB4	erb-b2 receptor tyrosine kinase 4	Inhibition	7.13	0.7%	Q15303
ERBB2	erb-b2 receptor tyrosine kinase 2	Inhibition	7.34	17.7%	P04626

Broader ChEMBL bioactivity targets: 21 (assay-derived). Sample: Receptor-interacting serine/threonine-protein kinase 3, Receptor tyrosine-protein kinase erbB-2, Alpha-2C adrenergic receptor, Epidermal growth factor receptor, Tyrosine-protein kinase JAK3, Muscarinic acetylcholine receptor M1, D(2) dopamine receptor, Sodium-dependent noradrenaline transporter, Receptor tyrosine-protein kinase erbB-2, Sodium-dependent dopamine transporter.

Bioactivity

ChEMBL activities: 52 potent at pChembl ≥ 5 of 60 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
EGFR	9.2	IC50	0.63	nM	CHEMBL_ACT_13446027
EGFR	8.74	IC50	1.8	nM	CHEMBL_ACT_15743462
EGFR	8.3	Kd	5	nM	CHEMBL_ACT_17898363
Q01279	8.24	IC50	5.8	nM	CHEMBL_ACT_26239137
EGFR	8.22	IC50	6	nM	CHEMBL_ACT_16668248
EGFR	8.22	IC50	6	nM	CHEMBL_ACT_16668417
EGFR	8.22	IC50	6	nM	CHEMBL_ACT_18784587
EGFR	8.22	IC50	6	nM	CHEMBL_ACT_18955305
EGFR	8.22	IC50	6	nM	CHEMBL_ACT_18997559
EGFR	8.22	IC50	6	nM	CHEMBL_ACT_19218783
EGFR	8.22	IC50	6	nM	CHEMBL_ACT_22892173
EGFR	8.22	IC50	6	nM	CHEMBL_ACT_23203420
EGFR	8.22	IC50	6	nM	CHEMBL_ACT_24805888
EGFR	8.22	IC50	6	nM	CHEMBL_ACT_24862044
EGFR	8.22	IC50	6	nM	CHEMBL_ACT_26039768
EGFR	8.22	IC50	6	nM	CHEMBL_ACT_26239125
EGFR	8.16	IC50	6.9	nM	CHEMBL_ACT_16352077
EGFR	8.16	IC50	6.9	nM	CHEMBL_ACT_26581692
EGFR	8	IC50	10	nM	CHEMBL_ACT_25472067
EGFR	8	IC50	10	nM	CHEMBL_ACT_25472072
EGFR	7.96	IC50	11	nM	CHEMBL_ACT_13446006
ERBB2	7.78	IC50	16.7	nM	CHEMBL_ACT_17621510
Q01279	7.7	IC50	19.95	nM	CHEMBL_ACT_25472063
EGFR	7.66	EC50	22	nM	CHEMBL_ACT_24805876
EGFR	7.4	EC50	40	nM	CHEMBL_ACT_24805879
P70424	7.39	IC50	41	nM	CHEMBL_ACT_26239141
EGFR	7.38	IC50	42	nM	CHEMBL_ACT_13446050
ERBB2	7.35	IC50	45	nM	CHEMBL_ACT_24805891
ERBB2	7.34	IC50	46	nM	CHEMBL_ACT_16668305
ERBB2	7.34	IC50	45.7	nM	CHEMBL_ACT_18784592

Target pathways

Aggregated over 3 target gene(s): EGFR, ERBB4, ERBB2.

Top Reactome pathways

59 total, by targets touching each:

Pathway	Targets	Genes
Signaling by ERBB2	3	EGFR, ERBB2, ERBB4
SHC1 events in ERBB2 signaling	3	EGFR, ERBB2, ERBB4
PIP3 activates AKT signaling	3	EGFR, ERBB2, ERBB4
GRB2 events in ERBB2 signaling	3	EGFR, ERBB2, ERBB4
PI3K events in ERBB2 signaling	3	EGFR, ERBB2, ERBB4
Constitutive Signaling by Aberrant PI3K in Cancer	3	EGFR, ERBB2, ERBB4
RAF/MAP kinase cascade	3	EGFR, ERBB2, ERBB4
ERBB2 Regulates Cell Motility	3	EGFR, ERBB2, ERBB4
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	3	EGFR, ERBB2, ERBB4
ERBB2 Activates PTK6 Signaling	3	EGFR, ERBB2, ERBB4
Downregulation of ERBB2 signaling	3	EGFR, ERBB2, ERBB4
Signaling by ERBB2 KD Mutants	3	EGFR, ERBB2, ERBB4
Signaling by ERBB2 TMD/JMD mutants	3	EGFR, ERBB2, ERBB4
Signaling by ERBB4	2	EGFR, ERBB4
PLCG1 events in ERBB2 signaling	2	EGFR, ERBB2
TFAP2 (AP-2) family regulates transcription of growth factors and their receptors	2	EGFR, ERBB2
Signaling by ERBB2 ECD mutants	2	EGFR, ERBB2
Developmental Lineage of Mammary Gland Myoepithelial Cells	2	EGFR, ERBB2
Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants	1	EGFR
PI3K events in ERBB4 signaling	1	ERBB4
SHC1 events in ERBB4 signaling	1	ERBB4
Nuclear signaling by ERBB4	1	ERBB4
Downregulation of ERBB4 signaling	1	ERBB4
GRB7 events in ERBB2 signaling	1	ERBB2
Downregulation of ERBB2:ERBB3 signaling	1	ERBB2
Signaling by EGFR	1	EGFR
GRB2 events in EGFR signaling	1	EGFR
GAB1 signalosome	1	EGFR
SHC1 events in EGFR signaling	1	EGFR
EGFR downregulation	1	EGFR

Dominant GO biological processes

GO term	Targets
signal transduction	3
cell surface receptor signaling pathway	3
epidermal growth factor receptor signaling pathway	3
neuron differentiation	3
negative regulation of apoptotic process	3
positive regulation of MAPK cascade	3
positive regulation of epithelial cell proliferation	3
cellular response to epidermal growth factor stimulus	3
protein phosphorylation	3
cell surface receptor protein tyrosine kinase signaling pathway	3
positive regulation of protein phosphorylation	2
positive regulation of cell population proliferation	2
positive regulation of cell growth	2
ERBB2-EGFR signaling pathway	2
phosphatidylinositol 3-kinase/protein kinase B signal transduction	2

Indications & clinical

Indications

16 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
non-small cell lung carcinoma	3	MONDO:0005233	EFO:0003060
lung neoplasm	3	MONDO:0021117	MONDO:0008903
head and neck squamous cell carcinoma	2	MONDO:0010150	EFO:0000181
carcinoma	2	MONDO:0004993	EFO:0000313
glioblastoma	2	MONDO:0018177	EFO:0000519
neoplasm	2	MONDO:0005070	EFO:0000616
upper aerodigestive tract neoplasm	2	MONDO:0005398	EFO:0004284
brain neoplasm	2	MONDO:0021211	EFO:0003833
squamous cell carcinoma	2	MONDO:0005096	EFO:0000707
penile neoplasm	2	MONDO:0006895	EFO:1001094
brain cancer	2	MONDO:0001657	MONDO:0001657
oral cavity cancer	1	MONDO:0005515	EFO:0005570
liver disorder	1	MONDO:0005154	EFO:0001421
colorectal neoplasm	1	MONDO:0005335	MONDO:0005575

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

Clinical trials

Total trials: 53.

Phase distribution

Phase	Trials
PHASE2	22
PHASE1	17
Not specified	5
PHASE3	4
PHASE1/PHASE2	3
PHASE4	1
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04511533	PHASE4	COMPLETED	Dacomitinib for Treatment of Patients in India With Metastatic Non Small Cell Lung Cancer With EGFR Activating Mutations
NCT06486142	PHASE3	RECRUITING	EGFR-mutated Lung Cancer in Randomized Investigator-Initiated Study
NCT01000025	PHASE3	COMPLETED	PF-00299804 in Stage IIIB or Stage IV Non-Small Cell Lung Cancer Not Responding to Standard Therapy for Advanced or Metastatic Cancer
NCT01360554	PHASE3	COMPLETED	ARCHER 1009 : A Study Of Dacomitinib (PF-00299804) Vs. Erlotinib In The Treatment Of Advanced Non-Small Cell Lung Cancer
NCT01774721	PHASE3	COMPLETED	ARCHER1050: A Study of Dacomitinib vs. Gefitinib in 1st-Line Treatment Of Advanced NSCLC.
NCT02925234	PHASE2	RECRUITING	The Drug Rediscovery Protocol (DRUP Trial)
NCT04027647	PHASE2	ACTIVE_NOT_RECRUITING	Phase 2 Study of Dacomitinib in NSCLC
NCT04423185	PHASE2	RECRUITING	PLATFORM Study of Precision Medicine for Rare Tumors
NCT04504071	PHASE2	ACTIVE_NOT_RECRUITING	Dacomitinib in Lung Cancer With Uncommon EGFR Mutations
NCT04946968	PHASE2	ACTIVE_NOT_RECRUITING	Phase-2 Dacomitinib Study on Patients With EGFR-Driven Advanced Solid Tumours With Low EGFR-AS1 IncRNA Expr or Other Novel Emerging Biomarkers
NCT05271916	PHASE1/PHASE2	RECRUITING	First-line Treatment With Dacomitinib Plus Anlotinib for Patients With Advanced NSCLC With EGFR 21L858R Mutations
NCT00548093	PHASE2	COMPLETED	PF-00299804 As A Single Agent, In Patients With Advanced Non-Small Cell Lung Cancer Who Have Failed Chemotherapy And Erlotinib
NCT00553254	PHASE2	COMPLETED	Trial Of PF-00299804 In Patients With Advanced Refractory Lung Cancer
NCT00768664	PHASE2	COMPLETED	Open-Label Trial Of Oral PF-00299804 By Continuous Dosing In Patients With Recurrent Or Metastatic Head And Neck Squamous Cell Cancer
NCT00769067	PHASE2	COMPLETED	A Randomized Trial Of PF-00299804 Taken Orally Versus Erlotinib Taken Orally For Treatment Of Advanced Non-Small Cell Lung Cancer That Has Progressed After One Or Two Prior Chemotherapy Regimen
NCT00818441	PHASE2	COMPLETED	Dacomitinib (PF-00299804) As A Single Oral Agent In Selected Patients With Adenocarcinoma Of The Lung
NCT01112527	PHASE2	COMPLETED	PF-00299804 in Adult Patients With Relapsed/Recurrent Glioblastoma
NCT01116843	PHASE1/PHASE2	COMPLETED	Study to Assess Biomarkers in Patients With Resectable Oral Cavity Cancer Randomized to Receive Preoperative Treatment
NCT01449201	PHASE2	COMPLETED	PF-00299804 in Patients With Head and Neck Squamous Cell Carcinoma
NCT01465802	PHASE2	COMPLETED	Study Of Dacomitinib (PF-00299804) In Advanced NSCLC Patients (Post Chemo Or Select First Line) To Evaluate Prophylactic Intervention On Derm And GI AEs And PRO
NCT01520870	PHASE2	COMPLETED	Safety and Efficacy of PF-299804 (Dacomitinib), a Pan-HER Irreversible Inhibitor, in Patients With Recurrent Glioblastoma With EGFR Amplification or Presence of EGFRvIII Mutation. A Phase II CT.
NCT01728233	PHASE2	COMPLETED	Dacomitinib (PF-00299804) in Advanced/Metastatic Squamous Cell Carcinoma of the Penis
NCT01858389	PHASE2	COMPLETED	A Study Of Dacomitinib (PF-00299804) In Patients With Advanced Non-Small Cell Lung Cancer
NCT02039336	PHASE1/PHASE2	COMPLETED	Dacomitinib Plus PD-0325901 in Advanced KRAS Mutant NSCLC
NCT02047747	PHASE2	TERMINATED	A Phase II Study of Dacomitinib in Progressive Brain Metastases
NCT02268747	PHASE2	UNKNOWN	Efficacy and Safety of Dacomitinib in the Treatment of Skin Squamous Cell Cancer
NCT02382796	PHASE2	COMPLETED	A Rollover Protocol of Dacomitinib For Patients In Japan
NCT04339829	PHASE2	UNKNOWN	An Open Label, Multicenter, Phase II Study of Dacomitinib for EGFR Mutated Non-Small Cell Lung Cancer (NSCLC) With Brain Metastases
NCT04675008	PHASE2	UNKNOWN	Central Nervous System(CNS) Efficacy of Dacomitinib
NCT04811001	PHASE2	UNKNOWN	Best EGFR-TKI Sequence in NSCLC Harboring EGFR Mutations
NCT00225121	PHASE1	COMPLETED	Study To Evaluate The Safety, Pharmacokinetics, And Pharmacodynamics Of PF-00299804 In Patients With Advanced Solid Tumors
NCT00728390	PHASE1	COMPLETED	A Safety And Efficacy Study Of The Combination Of Oral PF-00299804 And Intravenous CP-751,871 Given Every 3 Weeks
NCT00728468	PHASE1	COMPLETED	A Study To Test The Impact Of PF- 00299804 On How The Body Handles Dextromethorphan In Cancer Patients
NCT00783328	PHASE1	COMPLETED	A Study Of PF-00299804 In Patients In Japan With Advanced Malignant Solid Tumors
NCT00971191	PHASE1	TERMINATED	A Study In Patients Who Will Undergo Surgical Removal Of Non-Small Cell Lung Cancer To Evaluate Molecular Changes That Occur In Tumor Tissue After Short Term Exposure To PF-00299804
NCT01121575	PHASE1	COMPLETED	A Study Of Combined C- MET Inhibitor And PAN-HER Inhibitor (PF-02341066 And PF-00299804) In Patients With Non- Small Cell Lung Cancer
NCT01441128	PHASE1	TERMINATED	-02341066 and PF-00299804 for Advanced Non-Small Cell Lung Cancer
NCT01571388	PHASE1	COMPLETED	A Study To Compare Pharmacokinetics Of Dacomitinib (PF-00299804) Between Healthy Subjects And Subjects With Mild And Moderate Hepatic Impairment
NCT01702506	PHASE1	COMPLETED	Evaluation Of The Potential Effect That The Administration Of Food Or Antacid Medication May Have In The Oral Absorption Of Dacomitinib (PF-00299804)
NCT01737008	PHASE1	COMPLETED	Dacomitinib Plus Radiotherapy, With and Without Cisplatin in Patients With Squamous Cell Carcinoma of the Head and Neck

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.

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.

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

Molecule	Source	Status	Shared targets
AFATINIB	ChEMBL + PubChem	Phase 4 (approved)	EGFR, ERBB2, ERBB4
CRIZOTINIB	ChEMBL + PubChem	Phase 4 (approved)	EGFR, ERBB2, ERBB4
GEFITINIB	ChEMBL + PubChem	Phase 4 (approved)	EGFR, ERBB2, ERBB4
MOBOCERTINIB	ChEMBL + PubChem	Phase 4 (approved)	EGFR, ERBB2, ERBB4
SELUMETINIB	ChEMBL + PubChem	Phase 4 (approved)	EGFR, ERBB2, ERBB4
ZANUBRUTINIB	ChEMBL + PubChem	Phase 4 (approved)	EGFR, ERBB2, ERBB4
ACALABRUTINIB	ChEMBL	Phase 4 (approved)	EGFR, ERBB2, ERBB4
AFATINIB DIMALEATE	ChEMBL	Phase 4 (approved)	EGFR, ERBB2, ERBB4
BOSUTINIB	ChEMBL	Phase 4 (approved)	EGFR, ERBB2, ERBB4
BRIGATINIB	ChEMBL	Phase 4 (approved)	EGFR, ERBB2, ERBB4
DASATINIB	ChEMBL	Phase 4 (approved)	EGFR, ERBB2, ERBB4
ERLOTINIB	ChEMBL	Phase 4 (approved)	EGFR, ERBB2, ERBB4
IBRUTINIB	ChEMBL	Phase 4 (approved)	EGFR, ERBB2, ERBB4
LAPATINIB	ChEMBL	Phase 4 (approved)	EGFR, ERBB2, ERBB4
NERATINIB	ChEMBL	Phase 4 (approved)	EGFR, ERBB2, ERBB4
VANDETANIB	ChEMBL	Phase 4 (approved)	EGFR, ERBB2, ERBB4
ALISERTIB	ChEMBL	Phase 3	EGFR, ERBB2, ERBB4
ALVOCIDIB	ChEMBL	Phase 3	EGFR, ERBB2, ERBB4
CANERTINIB	ChEMBL	Phase 3	EGFR, ERBB2, ERBB4
CEDIRANIB	ChEMBL	Phase 3	EGFR, ERBB2, ERBB4
REMIBRUTINIB	ChEMBL	Phase 3	EGFR, ERBB2, ERBB4
AEE-788	ChEMBL	Phase 2	EGFR, ERBB2, ERBB4
ALLITINIB	ChEMBL	Phase 2	EGFR, ERBB2, ERBB4
ATUZABRUTINIB	ChEMBL	Phase 2	EGFR, ERBB2, ERBB4
CENISERTIB	ChEMBL	Phase 2	EGFR, ERBB2, ERBB4
DEFOSBARASERTIB	ChEMBL	Phase 2	EGFR, ERBB2, ERBB4
FORETINIB	ChEMBL	Phase 2	EGFR, ERBB2, ERBB4
ILORASERTIB	ChEMBL	Phase 2	EGFR, ERBB2, ERBB4
PELITINIB	ChEMBL	Phase 2	EGFR, ERBB2, ERBB4
R-406	ChEMBL	Phase 2	EGFR, ERBB2, ERBB4
TG100-115	ChEMBL	Phase 2	EGFR, ERBB2, ERBB4
VARLITINIB	ChEMBL	Phase 2	EGFR, ERBB2, ERBB4
Pazopanib	PubChem	Approved	EGFR, ERBB2, ERBB4
LAPATINIB DITOSYLATE	ChEMBL + PubChem	Phase 4 (approved)	EGFR, ERBB2
LAZERTINIB	ChEMBL + PubChem	Phase 4 (approved)	EGFR, ERBB2
RITLECITINIB	ChEMBL + PubChem	Phase 4 (approved)	ERBB2, ERBB4
ASTEMIZOLE	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
BITHIONOL	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
CABOZANTINIB	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
CHLORPROMAZINE	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
CLOTRIMAZOLE	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
COLISTIN	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
EBASTINE	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
ECONAZOLE	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
FEDRATINIB	ChEMBL	Phase 4 (approved)	EGFR, ERBB4
FLUPHENAZINE	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
HEXACHLOROPHENE	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
IMATINIB	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
MICONAZOLE	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
MIDOSTAURIN	ChEMBL	Phase 4 (approved)	EGFR, ERBB4
MITOXANTRONE	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
OSIMERTINIB	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
PONATINIB	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
SORAFENIB	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
TAMOXIFEN	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
TIRABRUTINIB	ChEMBL	Phase 4 (approved)	ERBB2, ERBB4
TRIBROMSALAN	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
TUCATINIB	ChEMBL	Phase 4 (approved)	EGFR, ERBB2
CANDESARTAN	ChEMBL	Phase 3	EGFR, ERBB2
ENCLOMIPHENE	ChEMBL	Phase 3	EGFR, ERBB2