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

Stem definition	Drug id	CAS RN
tyrosine kinase inhibitors	4866	1032900-25-6

Description:

Molecule	Description
Molfile Inchi Smiles Synonyms: NVP-LDK378-NX ceritinib zykadia LDK378	Ceritinib is a kinase inhibitor. Targets of ceritinib inhibition identified in either biochemical or cellular assays at clinically relevant concentrations include ALK, insulin-like growth factor 1 receptor (IGF-1R), insulin receptor (InsR), and ROS1. Among these, ceritinib is most active against ALK. Ceritinib inhibited autophosphorylation of ALK, ALK-mediated phosphorylation of the downstream signaling protein STAT3, and proliferation of ALK-dependent cancer cells in in vitro and in vivo assays. Molecular weight: 558.14 Formula: C28H36ClN5O3S CLOGP: 6.41 LIPINSKI: 2 HAC: 8 HDO: 3 TPSA: 105.24 ALOGS: -5.40 ROTB: 9 Status: ONP Legend: OFP - off patent OFM - off market ONP - on patent

Molecule

Description

Molfile Inchi Smiles

Synonyms:

NVP-LDK378-NX
ceritinib
zykadia
LDK378

Ceritinib is a kinase inhibitor. Targets of ceritinib inhibition identified in either biochemical or cellular assays at clinically relevant concentrations include ALK, insulin-like growth factor 1 receptor (IGF-1R), insulin receptor (InsR), and ROS1. Among these, ceritinib is most active against ALK. Ceritinib inhibited autophosphorylation of ALK, ALK-mediated phosphorylation of the downstream signaling protein STAT3, and proliferation of ALK-dependent cancer cells in in vitro and in vivo assays.

Molecular weight: 558.14
Formula: C28H36ClN5O3S
CLOGP: 6.41
LIPINSKI: 2
HAC: 8
HDO: 3
TPSA: 105.24
ALOGS: -5.40
ROTB: 9

Status: ONP

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

Drug dosage:

None

ADMET properties:

None

Approvals:

Date	Agency	Company	Orphan
Feb. 26, 2015	EMA
April 29, 2014	FDA	NOVARTIS PHARMS CORP

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
Malignant neoplasm progression	418.43	32.95	150	2419	64776	46618717
Non-small cell lung cancer stage IV	265.43	32.95	38	2531	199	46683294
Non-small cell lung cancer	228.31	32.95	49	2520	3095	46680398
Metastases to central nervous system	225.13	32.95	62	2507	11159	46672334
Diarrhoea	116.28	32.95	147	2422	559455	46124038
Nausea	80.44	32.95	138	2431	687316	45996177
Vomiting	72.23	32.95	105	2464	452689	46230804
Death	49.22	32.95	75	2494	335473	46348020
Lung adenocarcinoma	43.71	32.95	14	2555	4190	46679303
Pericarditis	41.35	32.95	22	2547	23905	46659588
Pericardial effusion	40.00	32.95	22	2547	25521	46657972
Alanine aminotransferase increased	39.09	32.95	35	2534	88416	46595077
Neoplasm progression	36.41	32.95	21	2548	26662	46656831
Decreased appetite	35.14	32.95	48	2521	193788	46489705
Lung neoplasm malignant	34.78	32.95	17	2552	15472	46668021
Aspartate aminotransferase increased	34.49	32.95	31	2538	78669	46604824
Hyperglycaemia	33.55	32.95	22	2547	35049	46648444

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
Malignant neoplasm progression	329.32	38.95	130	1555	72157	29878636
Non-small cell lung cancer	235.67	38.95	52	1633	3678	29947115
Metastases to central nervous system	148.74	38.95	41	1644	7243	29943550
Non-small cell lung cancer stage IV	121.58	38.95	19	1666	189	29950604
Diarrhoea	61.85	38.95	84	1601	334019	29616774
Nausea	49.33	38.95	71	1614	296886	29653907
Pericarditis	47.66	38.95	18	1667	8588	29942205
Lung neoplasm malignant	44.10	38.95	20	1665	15112	29935681
Metastases to liver	41.92	38.95	18	1667	11947	29938846

Pharmacologic Action:

Source	Code	Description
ATC	L01ED02	ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS ANTINEOPLASTIC AGENTS PROTEIN KINASE INHIBITORS Anaplastic lymphoma kinase (ALK) inhibitors
FDA MoA	N0000020001	Tyrosine Kinase Inhibitors
FDA EPC	N0000175605	Kinase Inhibitor
MeSH PA	D000970	Antineoplastic Agents
MeSH PA	D004791	Enzyme Inhibitors
MeSH PA	D047428	Protein Kinase Inhibitors
FDA MoA	N0000185504	Cytochrome P450 2C9 Inhibitors
FDA MoA	N0000190114	Cytochrome P450 3A Inhibitors
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

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	10.21	Basic
pKa2	2.49	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
150MG	ZYKADIA	NOVARTIS	N205755	April 29, 2014	DISCN	CAPSULE	ORAL	April 29, 2021	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.
150MG	ZYKADIA	NOVARTIS	N211225	March 18, 2019	RX	TABLET	ORAL	April 29, 2021	FDA HAS NOT RECOGNIZED ORPHAN-DRUG EXCLUSIVITY (ODE) FOR THIS DRUG, BUT IT CONTAINS THE SAME ACTIVE MOIETY OR MOIETIES AS ANOTHER DRUG(S) THAT WAS ELIGIBLE FOR ODE, AND ALSO SHARES ODE-PROTECTED USE(S) OR INDICATION(S) WITH THAT DRUG(S). AN APPLICATION SEEKING APPROVAL FOR THE SAME ACTIVE MOIETY OR MOIETIES, INCLUDING AN ANDA THAT CITES THIS NDA AS ITS BASIS OF SUBMISSION, MAY NOT BE APPROVED FOR SUCH ODE-PROTECTED USE(S) AND INDICATION(S)
150MG	ZYKADIA	NOVARTIS	N205755	April 29, 2014	DISCN	CAPSULE	ORAL	May 26, 2024	TREATMENT OF PATIENTS WITH METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC) WHOSE TUMORS ARE ANULLPLASTIC LYMPHOMA KINULLSE (ALK)-POSITIVE AS DETECTED BY AN FDA-APPROVED TEST
150MG	ZYKADIA	NOVARTIS	N211225	March 18, 2019	RX	TABLET	ORAL	May 26, 2024	FDA HAS NOT RECOGNIZED ORPHAN-DRUG EXCLUSIVITY (ODE) FOR THIS DRUG, BUT IT CONTAINS THE SAME ACTIVE MOIETY OR MOIETIES AS ANOTHER DRUG(S) THAT WAS ELIGIBLE FOR ODE, AND ALSO SHARES ODE-PROTECTED USE(S) OR INDICATION(S) WITH THAT DRUG(S). AN APPLICATION SEEKING APPROVAL FOR THE SAME ACTIVE MOIETY OR MOIETIES, INCLUDING AN ANDA THAT CITES THIS NDA AS ITS BASIS OF SUBMISSION, MAY NOT BE APPROVED FOR SUCH ODE-PROTECTED USE(S) AND INDICATION(S)

Bioactivity Summary:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Bioact source	MoA source
ALK tyrosine kinase receptor	Kinase	Q9UM73	ALK_HUMAN	INHIBITOR	IC50	9.70	SCIENTIFIC LITERATURE	SCIENTIFIC LITERATURE
Insulin receptor	Kinase	P06213	INSR_HUMAN	AGONIST	IC50	8.15	SCIENTIFIC LITERATURE
Testis-specific serine/threonine-protein kinase 1	Kinase	Q9BXA7	TSSK1_HUMAN		IC50	7.64	SCIENTIFIC LITERATURE
Fibroblast growth factor receptor 2	Kinase	P21802	FGFR2_HUMAN		IC50	6.59	CHEMBL
Tyrosine-protein kinase ABL1	Kinase	P00519	ABL1_HUMAN		IC50	5.90	CHEMBL
Receptor-type tyrosine-protein kinase FLT3	Kinase	P36888	FLT3_HUMAN		IC50	7.22	CHEMBL
Epidermal growth factor receptor	Kinase	P00533	EGFR_HUMAN		IC50	6.05	CHEMBL
Proto-oncogene tyrosine-protein kinase Src	Kinase	P12931	SRC_HUMAN		IC50	5.77	CHEMBL
Vascular endothelial growth factor receptor 2	Kinase	P35968	VGFR2_HUMAN		IC50	5.38	CHEMBL
Fibroblast growth factor receptor 3	Kinase	P22607	FGFR3_HUMAN		IC50	6.37	CHEMBL
Fibroblast growth factor receptor 4	Kinase	P22455	FGFR4_HUMAN		IC50	6.02	CHEMBL
Platelet-derived growth factor receptor alpha	Kinase	P16234	PGFRA_HUMAN		IC50	5.94	CHEMBL
Hepatocyte growth factor receptor	Kinase	P08581	MET_HUMAN		IC50	5.87	CHEMBL
Tyrosine-protein kinase JAK2	Kinase	O60674	JAK2_HUMAN		IC50	6.21	CHEMBL
Tyrosine-protein kinase JAK1	Kinase	P23458	JAK1_HUMAN		IC50	5.43	CHEMBL
Tyrosine-protein kinase SYK	Kinase	P43405	KSYK_HUMAN		IC50	5.52	CHEMBL
Tyrosine-protein kinase BTK	Kinase	Q06187	BTK_HUMAN		IC50	5.47	CHEMBL
Tyrosine-protein kinase Fgr	Kinase	P09769	FGR_HUMAN		IC50	5.71	CHEMBL
Tyrosine-protein kinase JAK3	Kinase	P52333	JAK3_HUMAN		IC50	5.10	CHEMBL
Potassium voltage-gated channel subfamily H member 2	Ion channel	Q12809	KCNH2_HUMAN		IC50	5.90	CHEMBL
High affinity nerve growth factor receptor	Kinase	P04629	NTRK1_HUMAN		IC50	5.56	CHEMBL
Mast/stem cell growth factor receptor Kit	Kinase	P10721	KIT_HUMAN		IC50	5.89	CHEMBL
MAP kinase-interacting serine/threonine-protein kinase 2	Kinase	Q9HBH9	MKNK2_HUMAN		IC50	5.65	CHEMBL
Tyrosine-protein kinase Lyn	Kinase	P07948	LYN_HUMAN		IC50	6.08	CHEMBL
Tyrosine-protein kinase ZAP-70	Kinase	P43403	ZAP70_HUMAN		IC50	5.01	CHEMBL
Cyclin-dependent kinase 2	Kinase	P24941	CDK2_HUMAN		IC50	5.40	CHEMBL
Proto-oncogene tyrosine-protein kinase ROS	Kinase	P08922	ROS1_HUMAN		IC50	6.85	CHEMBL
Rho-associated protein kinase 2	Kinase	O75116	ROCK2_HUMAN		IC50	5.90	CHEMBL
Transcription factor ETV6	Transcription factor	P41212	ETV6_HUMAN		IC50	5.49	CHEMBL
Proto-oncogene tyrosine-protein kinase receptor Ret	Kinase	P07949	RET_HUMAN		IC50	6.40	CHEMBL
Tyrosine-protein kinase Lck	Kinase	P06239	LCK_HUMAN		IC50	6.25	CHEMBL
BDNF/NT-3 growth factors receptor	Kinase	Q16620	NTRK2_HUMAN		IC50	5.74	CHEMBL
Insulin-like growth factor 1 receptor	Kinase	P08069	IGF1R_HUMAN		IC50	8.10	SCIENTIFIC LITERATURE
Cyclin-dependent kinase 4	Kinase	P11802	CDK4_HUMAN		IC50	5.33	CHEMBL

External reference:

ID	Source
D10551	KEGG_DRUG
4033301	VUID
N0000190753	NUI
4033301	VANDF
C3818721	UMLSCUI
CHEBI:78432	CHEBI
4MK	PDB_CHEM_ID
CHEMBL2403108	ChEMBL_ID
DB09063	DRUGBANK_ID
C586847	MESH_SUPPLEMENTAL_RECORD_UI
57379345	PUBCHEM_CID
7397	IUPHAR_LIGAND_ID
9817	INN_ID
K418KG2GET	UNII
1535457	RXNORM
219616	MMSL
30281	MMSL
d08255	MMSL
015504	NDDF
703146007	SNOMEDCT_US
704310000	SNOMEDCT_US

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
ZYKADIA	HUMAN PRESCRIPTION DRUG LABEL	1	0078-0640	CAPSULE	150 mg	ORAL	NDA	28 sections
ZYKADIA	HUMAN PRESCRIPTION DRUG LABEL	1	0078-0694	TABLET, FILM COATED	150 mg	ORAL	NDA	28 sections