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

Stem definition	Drug id	CAS RN
tyrosine kinase inhibitors	4937	1256580-46-7

Description:

Molecule	Description
Molfile Inchi Smiles Synonyms: alectinib alectinib hydrochloride alecensa CH5424802 alectinib HCl RO5424802 RO-5424802	Alectinib is a tyrosine kinase inhibitor that targets ALK and RET. In nonclinical studies, alectinib inhibited ALK phosphorylation and ALK-mediated activation of the downstream signaling proteins STAT3 and AKT, and decreased tumor cell viability in multiple cell lines harboring ALK fusions, amplifications, or activating mutations. The major active metabolite of alectinib, M4, showed similar in vitro potency and activity. Molecular weight: 482.63 Formula: C30H34N4O2 CLOGP: 5.53 LIPINSKI: 1 HAC: 6 HDO: 1 TPSA: 72.36 ALOGS: -4.66 ROTB: 3 Status: ONP Legend: OFP - off patent OFM - off market ONP - on patent

Molecule

Description

Molfile Inchi Smiles

Synonyms:

alectinib
alectinib hydrochloride
alecensa
CH5424802
alectinib HCl
RO5424802
RO-5424802

Alectinib is a tyrosine kinase inhibitor that targets ALK and RET. In nonclinical studies, alectinib inhibited ALK phosphorylation and ALK-mediated activation of the downstream signaling proteins STAT3 and AKT, and decreased tumor cell viability in multiple cell lines harboring ALK fusions, amplifications, or activating mutations. The major active metabolite of alectinib, M4, showed similar in vitro potency and activity.

Molecular weight: 482.63
Formula: C30H34N4O2
CLOGP: 5.53
LIPINSKI: 1
HAC: 6
HDO: 1
TPSA: 72.36
ALOGS: -4.66
ROTB: 3

Status: ONP

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

Drug dosage:

None

ADMET properties:

Property	Value	Reference
Vd (Volume of distribution)	6.35 L/kg	Lombardo F, Berellini G, Obach RS
CL (Clearance)	7.69 mL/min/kg	Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma)	0.00 %	Lombardo F, Berellini G, Obach RS
t_half (Half-life)	11.70 hours	Lombardo F, Berellini G, Obach RS

Approvals:

Date	Agency	Company
Feb. 16, 2017	EMA	Roche Registration Limited
Dec. 11, 2015	FDA	HOFFMAN-LA ROCHE
July 4, 2014	PMDA

FDA Adverse Event Reporting System (Female)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Neoplasm progression	131.24	33.43	47	1873	26636	46657506
Metastases to central nervous system	91.75	33.43	29	1891	11192	46672950
Constipation	64.90	33.43	55	1865	174042	46510100
Death	59.97	33.43	71	1849	335477	46348665
Blood creatine phosphokinase increased	41.42	33.43	21	1899	27703	46656439
Pleural effusion	38.82	33.43	30	1890	82922	46601220
Pneumonitis	35.23	33.43	19	1901	28401	46655741

FDA Adverse Event Reporting System (Male)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Neoplasm progression	69.22	36.56	27	1295	17996	29933160
Death	63.97	36.56	78	1244	357205	29593951
Pneumonitis	52.10	36.56	25	1297	27429	29923727
Metastases to central nervous system	46.93	36.56	16	1306	7268	29943888
Interstitial lung disease	43.24	36.56	29	1293	60168	29890988

Pharmacologic Action:

Source	Code	Description
ATC	L01ED03	ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS ANTINEOPLASTIC AGENTS PROTEIN KINASE INHIBITORS Anaplastic lymphoma kinase (ALK) inhibitors
FDA MoA	N0000175082	Kinase Inhibitors
FDA EPC	N0000175605	Kinase Inhibitor
CHEBI has role	CHEBI:35610	cytostatic
CHEBI has role	CHEBI:62434	alk inhibitor

Drug Use (View source of the data)

Disease	Relation	SNOMED_ID	DOID
Non-small cell lung cancer	indication	254637007	DOID:3908
Anaplastic lymphoma kinase positive anaplastic large cell lymphoma	indication	738770003

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	11.42	acidic
pKa2	7.47	Basic
pKa3	4.89	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
EQ 150MG BASE	ALECENSA	HOFFMANN-LA ROCHE	N208434	Dec. 11, 2015	RX	CAPSULE	ORAL	Dec. 11, 2022	TREATMENT OF PATIENTS WITH ANULLPLASTIC LYMPHOMA KINULLSE (ALK)-POSITIVE METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC), WHO HAVE PROGRESSED ON OR ARE INTOLERANT TO CRIZOTINIB
EQ 150MG BASE	ALECENSA	HOFFMANN-LA ROCHE	N208434	Dec. 11, 2015	RX	CAPSULE	ORAL	Nov. 6, 2024	FOR TREATMENT OF PATIENTS WITH ANULLPLASTIC LYMPHOMA KINULLSE (ALK) POSITIVE, METASTATIC NON-SMALL-CELL LUNG CANCER (NSCLC) AS DETECTED BY AN FDA APPROVED TEST, EXCLUDING PATIENTS WHO HAVE PROGRESSED ON OR ARE INTOLERANT TO CRIZOTINIB

Bioactivity Summary:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Bioact source	MoA source
Proto-oncogene tyrosine-protein kinase receptor Ret	Kinase	P07949	RET_HUMAN	INHIBITOR	IC50	8.32	SCIENTIFIC LITERATURE	DRUG LABEL
ALK tyrosine kinase receptor	Kinase	Q9UM73	ALK_HUMAN	INHIBITOR	IC50	8.72	SCIENTIFIC LITERATURE	DRUG LABEL
Vascular endothelial growth factor receptor 2	Kinase	P35968	VGFR2_HUMAN		IC50	5.85	CHEMBL

External reference:

ID	Source
LIJ4CT1Z3Y	UNII
D10450	KEGG_DRUG
1256589-74-8	SECONDARY_CAS_RN
4035251	VANDF
C4060047	UMLSCUI
CHEBI:62268	CHEBI
EMH	PDB_CHEM_ID
CHEMBL1738797	ChEMBL_ID
CHEMBL3707320	ChEMBL_ID
DB11363	DRUGBANK_ID
49806720	PUBCHEM_CID
9699	INN_ID
C582670	MESH_SUPPLEMENTAL_RECORD_UI
7739	IUPHAR_LIGAND_ID
1727454	RXNORM
237548	MMSL
31372	MMSL
d08405	MMSL
016628	NDDF
016629	NDDF
716039000	SNOMEDCT_US
716040003	SNOMEDCT_US
781316007	SNOMEDCT_US

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
ALECENSA	HUMAN PRESCRIPTION DRUG LABEL	1	50242-130	CAPSULE	150 mg	ORAL	NDA	28 sections