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

Stem definition	Drug id	CAS RN
tyrosine kinase inhibitors	5306	1254053-43-4

Description:

Molecule	Description
Molfile Inchi Smiles Synonyms: gilteritinib fumarate gilteritinib xospata ASP2215	Gilteritinib is a small molecule that inhibits multiple receptor tyrosine kinases, including FMS-like tyrosine kinase 3 (FLT3). Gilteritinib demonstrated the ability to inhibit FLT3 receptor signaling and proliferation in cells exogenously expressing FLT3 including FLT3-ITD, tyrosine kinase domain mutations (TKD) FLT3-D835Y and FLT3-ITD-D835Y, and it induced apoptosis in leukemic cells expressing FLT3-ITD. Molecular weight: 552.72 Formula: C29H44N8O3 CLOGP: 2.12 LIPINSKI: 2 HAC: 11 HDO: 3 TPSA: 121.11 ALOGS: -4.39 ROTB: 9 Status: ONP Legend: OFP - off patent OFM - off market ONP - on patent

Molecule

Description

Molfile Inchi Smiles

Synonyms:

gilteritinib fumarate
gilteritinib
xospata
ASP2215

Gilteritinib is a small molecule that inhibits multiple receptor tyrosine kinases, including FMS-like tyrosine kinase 3 (FLT3). Gilteritinib demonstrated the ability to inhibit FLT3 receptor signaling and proliferation in cells exogenously expressing FLT3 including FLT3-ITD, tyrosine kinase domain mutations (TKD) FLT3-D835Y and FLT3-ITD-D835Y, and it induced apoptosis in leukemic cells expressing FLT3-ITD.

Molecular weight: 552.72
Formula: C29H44N8O3
CLOGP: 2.12
LIPINSKI: 2
HAC: 11
HDO: 3
TPSA: 121.11
ALOGS: -4.39
ROTB: 9

Status: ONP

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

Drug dosage:

None

ADMET properties:

None

Approvals:

Date	Agency	Company
Sept. 21, 2018	PMDA	Astellas Pharma Inc
Nov. 28, 2018	FDA	ASTELLAS
Oct. 24, 2019	EMA	ASTELLAS PHARMA EUROPE BV

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
Febrile neutropenia	243.27	43.85	97	1429	94530	46590006
Acute myeloid leukaemia	189.29	43.85	52	1474	15726	46668810
Hepatic function abnormal	141.62	43.85	50	1476	34371	46650165
Myelosuppression	109.17	43.85	29	1497	7674	46676862
Platelet count decreased	104.41	43.85	55	1471	99969	46584567
Cytopenia	94.82	43.85	26	1500	7742	46676794
Neutrophil count decreased	85.48	43.85	37	1489	43389	46641147
Differentiation syndrome	84.70	43.85	16	1510	895	46683641
Acute myeloid leukaemia recurrent	54.96	43.85	12	1514	1384	46683152
Acute febrile neutrophilic dermatosis	52.12	43.85	13	1513	2672	46681864
Blast cell count increased	44.19	43.85	8	1518	353	46684183

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
Acute myeloid leukaemia	208.36	41.88	62	1303	17944	29933169
Febrile neutropenia	180.23	41.88	90	1275	106603	29844510
Myelosuppression	176.76	41.88	45	1320	7277	29943836
Hepatic function abnormal	115.98	41.88	50	1315	41895	29909218
Platelet count decreased	91.98	41.88	58	1307	106071	29845042
Differentiation syndrome	58.68	41.88	13	1352	1147	29949966

Pharmacologic Action:

Source	Code	Description
ATC	L01EX13	ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS ANTINEOPLASTIC AGENTS PROTEIN KINASE INHIBITORS Other protein kinase inhibitors
CHEBI has role	CHEBI:35610	cytostatic
CHEBI has role	CHEBI:62434	alk inhibitor
CHEBI has role	CHEBI:68495	type i programmed cell-death inducer

Drug Use (View source of the data)

Disease	Relation	SNOMED_ID	DOID
Acute myeloid leukemia, disease	indication	91861009

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	11.78	acidic
pKa2	8.76	Basic
pKa3	5.0	Basic
pKa4	4.38	Basic
pKa5	3.81	Basic
pKa6	0.35	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 40MG BASE	XOSPATA	ASTELLAS	N211349	Nov. 28, 2018	RX	TABLET	ORAL	Nov. 28, 2023	NEW CHEMICAL ENTITY
EQ 40MG BASE	XOSPATA	ASTELLAS	N211349	Nov. 28, 2018	RX	TABLET	ORAL	Nov. 28, 2025	INDICATED FOR THE TREATMENT OF ADULT PATIENTS WHO HAVE RELAPSED OR REFRACTORY ACUTE MYELOID LEUKEMIA (AML) WITH A FMS-LIKE TYROSINE KINULLSE 3 (FLT3) MUTATION AS DETECTED BY AN FDA-APPROVED TEST

Bioactivity Summary:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Mechanism action	Bioact source	MoA source
Receptor-type tyrosine-protein kinase FLT3	Kinase	P36888	FLT3_HUMAN	INHIBITOR	IC50	8.30		SCIENTIFIC LITERATURE	DRUG LABEL

External reference:

ID	Source
1254053-84-3	SECONDARY_CAS_RN
4038030	VANDF
C3896738	UMLSCUI
CHEBI:145372	CHEBI
C6F	PDB_CHEM_ID
CHEMBL3301622	ChEMBL_ID
CHEMBL3301603	ChEMBL_ID
DB12141	DRUGBANK_ID
D10709	KEGG_DRUG
49803313	PUBCHEM_CID
C000609080	MESH_SUPPLEMENTAL_RECORD_UI
8708	IUPHAR_LIGAND_ID
10048	INN_ID
66D92MGC8M	UNII
2105806	RXNORM
299484	MMSL
35657	MMSL
35755	MMSL
d09076	MMSL
017854	NDDF
017855	NDDF
782974005	SNOMEDCT_US
782987004	SNOMEDCT_US

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
Xospata	HUMAN PRESCRIPTION DRUG LABEL	1	0469-1425	TABLET	40 mg	ORAL	NDA	29 sections