dacomitinib Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definition	Drug id	CAS RN
tyrosine kinase inhibitors	5297	1110813-31-4

Description:

Molecule	Description
Molfile Inchi Smiles Synonyms: dacomitinib dacomitinib hydrate vizimpro PF-00299804-03 PF-00299804 PF-299 PF-299804 PF-804	Dacomitinib is an irreversible inhibitor of the kinase activity of the human EGFR family (EGFR/HER1, HER2, and HER4) and certain EGFR activating mutations (exon 19 deletion or the exon 21 L858R substitution mutation). In vitro dacomitinib also inhibited the activity of DDR1, EPHA6, LCK, DDR2, and MNK1 at clinically relevant concentrations. Molecular weight: 469.95 Formula: C24H25ClFN5O2 CLOGP: 5.75 LIPINSKI: 1 HAC: 7 HDO: 2 TPSA: 79.38 ALOGS: -4.73 ROTB: 7 Status: ONP Legend: OFP - off patent OFM - off market ONP - on patent

Molecule

Description

Molfile Inchi Smiles

Synonyms:

dacomitinib
dacomitinib hydrate
vizimpro
PF-00299804-03
PF-00299804
PF-299
PF-299804
PF-804

Dacomitinib is an irreversible inhibitor of the kinase activity of the human EGFR family (EGFR/HER1, HER2, and HER4) and certain EGFR activating mutations (exon 19 deletion or the exon 21 L858R substitution mutation). In vitro dacomitinib also inhibited the activity of DDR1, EPHA6, LCK, DDR2, and MNK1 at clinically relevant concentrations.

Molecular weight: 469.95
Formula: C24H25ClFN5O2
CLOGP: 5.75
LIPINSKI: 1
HAC: 7
HDO: 2
TPSA: 79.38
ALOGS: -4.73
ROTB: 7

Status: ONP

Legend:
OFP - off patent
OFM - off market
ONP - on patent

Drug dosage:

None

ADMET properties:

None

Approvals:

Date	Agency	Company	Orphan
Feb. 4, 2019	EMA	PFIZER EUROPE MA EEIG
Sept. 27, 2018	FDA	PFIZER INC

FDA Adverse Event Reporting System (Female)

None

FDA Adverse Event Reporting System (Male)

None

Pharmacologic Action:

Source	Code	Description
ATC	L01EB07	ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS ANTINEOPLASTIC AGENTS PROTEIN KINASE INHIBITORS Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors
CHEBI has role	CHEBI:35610	cytostatic
CHEBI has role	CHEBI:74440	egfr inhibitor

Drug Use (View source of the data)

Disease	Relation	SNOMED_ID	DOID
Non-small cell lung cancer, positive for epidermal growth factor receptor expression	indication	426964009

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	11.02	acidic
pKa2	9.12	Basic
pKa3	4.78	Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

Formulation strength	Trade name	Applicant	Application number	Approval date	Type	Dose form	Route	Exclusivity date	Description
15MG	VIZIMPRO	PFIZER	N211288	Sept. 27, 2018	RX	TABLET	ORAL	Sept. 27, 2023	NEW CHEMICAL ENTITY
30MG	VIZIMPRO	PFIZER	N211288	Sept. 27, 2018	RX	TABLET	ORAL	Sept. 27, 2023	NEW CHEMICAL ENTITY
45MG	VIZIMPRO	PFIZER	N211288	Sept. 27, 2018	RX	TABLET	ORAL	Sept. 27, 2023	NEW CHEMICAL ENTITY
15MG	VIZIMPRO	PFIZER	N211288	Sept. 27, 2018	RX	TABLET	ORAL	Sept. 27, 2025	FIRST-LINE TREATMENT OF PATIENTS WITH METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC) WITH EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) EXON 19 DELETION OR EXON 21 L858R SUBSTITUTION MUTATIONS AS DETECTED BY AN FDA-APPROVED TEST
15MG	VIZIMPRO	PFIZER	N211288	Sept. 27, 2018	RX	TABLET	ORAL	Sept. 27, 2025	INDICATED FOR THE FIRST-LINE TREATMENT OF PATIENTS WITH METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC) WITH EPIDERMAL GROWTH FACTOR (EGFR) EXON 19 DELETION OR EXON 21 L858R SUBSTITUTION MUTATIONS AS DETECTED BY AN FDA-APPROVED TEST
30MG	VIZIMPRO	PFIZER	N211288	Sept. 27, 2018	RX	TABLET	ORAL	Sept. 27, 2025	FIRST-LINE TREATMENT OF PATIENTS WITH METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC) WITH EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) EXON 19 DELETION OR EXON 21 L858R SUBSTITUTION MUTATIONS AS DETECTED BY AN FDA-APPROVED TEST
30MG	VIZIMPRO	PFIZER	N211288	Sept. 27, 2018	RX	TABLET	ORAL	Sept. 27, 2025	INDICATED FOR THE FIRST-LINE TREATMENT OF PATIENTS WITH METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC) WITH EPIDERMAL GROWTH FACTOR (EGFR) EXON 19 DELETION OR EXON 21 L858R SUBSTITUTION MUTATIONS AS DETECTED BY AN FDA-APPROVED TEST
45MG	VIZIMPRO	PFIZER	N211288	Sept. 27, 2018	RX	TABLET	ORAL	Sept. 27, 2025	FIRST-LINE TREATMENT OF PATIENTS WITH METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC) WITH EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) EXON 19 DELETION OR EXON 21 L858R SUBSTITUTION MUTATIONS AS DETECTED BY AN FDA-APPROVED TEST
45MG	VIZIMPRO	PFIZER	N211288	Sept. 27, 2018	RX	TABLET	ORAL	Sept. 27, 2025	INDICATED FOR THE FIRST-LINE TREATMENT OF PATIENTS WITH METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC) WITH EPIDERMAL GROWTH FACTOR (EGFR) EXON 19 DELETION OR EXON 21 L858R SUBSTITUTION MUTATIONS AS DETECTED BY AN FDA-APPROVED TEST

Bioactivity Summary:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Bioact source	MoA source
Epidermal growth factor receptor	Kinase	P00533	EGFR_HUMAN	INHIBITOR	IC50	8.22	SCIENTIFIC LITERATURE	DRUG LABEL
Receptor tyrosine-protein kinase erbB-2	Kinase	P04626	ERBB2_HUMAN	INHIBITOR	IC50	7.34	SCIENTIFIC LITERATURE	DRUG LABEL
Receptor tyrosine-protein kinase erbB-4	Kinase	Q15303	ERBB4_HUMAN	INHIBITOR	IC50	7.13	SCIENTIFIC LITERATURE	DRUG LABEL

External reference:

ID	Source
1042385-75-0	SECONDARY_CAS_RN
4037910	VANDF
C2987430	UMLSCUI
CHEBI:132268	CHEBI
1C9	PDB_CHEM_ID
CHEMBL2105719	ChEMBL_ID
CHEMBL2110732	ChEMBL_ID
DB11963	DRUGBANK_ID
D09883	KEGG_DRUG
C525726	MESH_SUPPLEMENTAL_RECORD_UI
11511120	PUBCHEM_CID
7422	IUPHAR_LIGAND_ID
5092U85G58	UNII
2058849	RXNORM
293963	MMSL
35285	MMSL
d08999	MMSL
017767	NDDF
781492009	SNOMEDCT_US
781495006	SNOMEDCT_US

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
Vizimpro	HUMAN PRESCRIPTION DRUG LABEL	1	0069-0197	TABLET, FILM COATED	15 mg	ORAL	NDA	28 sections
Vizimpro	HUMAN PRESCRIPTION DRUG LABEL	1	0069-1198	TABLET, FILM COATED	30 mg	ORAL	NDA	28 sections
Vizimpro	HUMAN PRESCRIPTION DRUG LABEL	1	0069-2299	TABLET, FILM COATED	45 mg	ORAL	NDA	28 sections
Vizimpro	HUMAN PRESCRIPTION DRUG LABEL	1	63539-197	TABLET, FILM COATED	15 mg	ORAL	NDA	27 sections