General
Preferred name
GILTERITINIB
Synonyms
Gilteritinib fumarate, ASP-2215 HEMIFUMARATE, ASP-2215 ()
ASP2215 hemifumarate ()
Gilteritinib hemifumarate ()
ASP2215 ()
Gilteritinib (ASP2215) ()
GilteritinibASP-2215ASP2215A-1371 ()
GILTERITINIB FUMARATE ()
ASP-2215 ()
Gilteritinib ()
Xospata ()
ASP-2215 HEMIFUMARATE ()
P&D ID
PD050507
CAS
1254053-43-4
1254053-84-3
Tags
available
drug
Approved by
EMA
FDA
PMDA
First approval
2018
Drug indication
Neoplasm
Acute myeloid leukemia
Acute myeloid leukaemia
Drug Status
approved
investigational
Max Phase
4.0
Probe control
Probe control not defined
Orthogonal probes
0
No orthogonal probes found
Similar probes
0
No structurally similar probes found
Structure
P&D probe-likeness score
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
PHARMACODYNAMICS
In preclinical trials, gilteritinib demonstrate an IC50 for the wild-type receptor of 5 nM, 0.7-1.8 nM for ITD-mutated and comparable inhibition to other therapies in the TKD-mutated. As well, data showed a gilteritinib-driven inhibition of the receptor tyrosine kinase AXL which is known to modulate the activity of FLT3 in acute myeloid leukemia.[A40044] Another important result _in vivo_ was the localization in high levels in xenografted tumors which indicated high selectivity.[A40048]; ; In phase 1/2 clinical trials, gilteritinib was shown to present a composite complete response of 41%, an overall response rate of 52%, a median duration of response of 20 weeks with a median overall survival of 31 weeks.[A40036]; ; In phase III clinical trials, gilteritinib reported a complete remission or complete remission with partial hematologic recovery in 21% of the patients.[L4830]
MOA
Gilteritinib is a potent selective inhibitor of both of the mutations, internal tandem duplication (ITD) and tyrosine kinase domain (TKD), of the FLT3 receptor.[A40039] In the same note, gilteritinib also inhibits AXL and ALK tyrosine kinases.[A40040] FLT3 and AXL are molecules involved in the growth of cancer cells.[A40043] The activity of gilteritinib permits an inhibition of the phosphorylation of FLT3 and its downstream targets such as STAT5, ERK and AKT.[A40048]; ; The interest in FLT3 transmembrane tyrosine kinases was raised when studies reported that approximately 30% of the patients with acute myeloid leukemia presented a mutationally activated isoform.[A40036] As well, the mutation ITD is associated with poor patient outcomes while the mutation TKD produces a resistance mechanism to FLT3 tyrosine kinase inhibitors and the AXL tyrosine kinase tends to produce a resistance mechanism to chemotherapies.[A40043]
INDICATION
Gilteritinib is indicated for the treatment of adult patients who have relapsed or refractory acute myeloid leukemia with an FLT3 mutation detected by an FDA-approved test. This indication was expanded for a companion diagnostic to include use with gilteritinib such as the LeukoStrat CDx FLT3 Mutation Assay.[L4830]; ; Acute myeloid leukemia is cancer that impacts the blood and bone marrow with a rapid progression. This condition produces low numbers of normal blood cells and the requirement of continuous need for transfusions.[L4832]
ABSORPTION
In preclinical trials, the maximal plasma concentration of gilteritinib was observed 2 hours after oral administration and followed by a maximal intratumor concentration after 4-8 hours. The maximum concentration, as well as the AUC, were modified correspondingly with the dose and were reported to be 374 ng/ml and 6943 ng.h/ml, respectively.[A40048] The steady-state plasma level is reached within 15 days of dosing with an approximate 10-fold bioaccumulation.[L4833]; ; In a fasted state in humans, the tmax is reported to be of 4-6 hours. The Cmax and AUC were decreased by 26% and 10% respectively by the co-ingestion of a high-fat meal with a tmax delay of 2 hours.[L4834]
DESCRIPTION
Gilteritinib is an orally bioavailable inhibitor of the receptor tyrosine kinases (RTKs) FMS-related tyrosine kinase 3 (FLT3), AXL and anaplastic lymphoma kinase (ALK) , with clinical antineoplastic activity. Gilteritinib inhibits the activity of FLT3-activating mutations which are one of the most common genetic alterations in acute myeloid leukemia (AML).
SARS-CoV-2: AXL is a kinase upstream of p38 MAP kinases. p38 activity has been reported to be upregulated following SARS-CoV-2 infection of host cells in vitro, and gilteritinib produces an antiviral effect (IC50= 807 nM) . (GtoPdb)
SARS-CoV-2: AXL is a kinase upstream of p38 MAP kinases. p38 activity has been reported to be upregulated following SARS-CoV-2 infection of host cells in vitro, and gilteritinib produces an antiviral effect (IC50= 807 nM) . (GtoPdb)
DESCRIPTION
Gilteritinib is an orally bioavailable inhibitor of the receptor tyrosine kinases (RTKs) FMS-related tyrosine kinase 3 (FLT3), AXL and anaplastic lymphoma kinase (ALK), with potential antineoplastic activity.
PRICE
128
DESCRIPTION
Gilteritinib (ASP2215) is a potent inhibitor of FMS-related tyrosine kinase 3 (FLT3) and AXL tyrosine kinase receptors (IC50 = 0.29 nM and <1 nM, respectively). In preclinical studies, gilteritinib demonstrated strong antileukemic and antitumor effects. Gilteritinib is currently in several Phase 3 clinical trials for acute myeloid leukemia.
DESCRIPTION
Gilteritinib (ASP2215) hemifumarate is a potent and ATP-competitive FLT3/AXL inhibitor with IC50 of 0.29 nM/0.73 nM, respectively.
PRICE
133
DESCRIPTION
On november 28, 2018, the FDA approved gilteritinib to treat patients who have relapsed or refractory acute myeloid leukemia (AML)
(PKIDB)
DESCRIPTION
Gilteritinib is a potent selective inhibitor of both of the mutations, internal tandem duplication and tyrosine kinase domain, of the FLT3 receptor. It is used to treat relapsed or refractory acute myeloid leukemia.
(Enamine Bioactive Compounds)
DESCRIPTION
Gilteritinib hemifumarate (ASP2215 hemifumarate) is a potent ATP-competitive dual FLT3 (IC50: 0.29 nM) and AXL (IC50: 0.73 nM) inhibitor for the treatment of relapsed or refractory FLT3 mutant AML.
(TargetMol Bioactive Compound Library)
[[ p.pathway_name ]]
[[ compound.targets[tid].gene_name ]]
Cell lines
12
Organisms
2
Compound Sets
26
AdooQ Bioactive Compound Library
Cayman Chemical Bioactives
ChEMBL Approved Drugs
ChEMBL Drugs
Clinical kinase drugs
CZ-OPENSCREEN Bioactive Library
Drug Repurposing Hub
DrugBank
DrugBank Approved Drugs
DrugCentral
DrugCentral Approved Drugs
Enamine Bioactive Compounds
Guide to Pharmacology
LSP-MoA library (Laboratory of Systems Pharmacology)
LSP-OptimalKinase library (Laboratory of Systems Pharmacology)
Mcule NIBR MoA Box Subset
NCATS Inxight Approved Drugs
NIH Approved Oncology Drugs
Novartis Chemogenetic Library (NIBR MoA Box)
PKIDB
ReFrame library
Selleckchem Bioactive Compound Library
TargetMol Bioactive Compound Library
[[ a.name ]]
[[ ligand_id ]]
free of charge
External IDs
47
Molecular Weight
552.35
Hydrogen Bond Acceptors
10
Hydrogen Bond Donors
3
Rotatable Bonds
9
Ring Count
5
Aromatic Ring Count
2
cLogP
2.7
TPSA
121.11
Fraction CSP3
0.62
Chiral centers
0.0
Largest ring
6.0
QED
0.43
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Targets
FLT3,AXL
Target
FLT3
AXL
TAM Receptor
Axl,FLT3
ALK
Member status
member
MOA
FLT3/AXL inhibitor
FLT3 inhibitor
Therapeutic Class
Anticancer Agents
Pathway
Protein Tyrosine Kinase/RTK
Angiogenesis
Tyrosine Kinase/Adaptors
Source data
