Gilteritinib - CAS 1254053-43-4
Catalog number: B0084-462531
Category: Inhibitor
Please be kindly noted products are not for therapeutic use. We do not sell to patients.
Molecular Formula:
C29H44N8O3
Molecular Weight:
552.724
COA:
Inquire
Targets:
FLT3
Description:
Gilteritinib, also known as (ASP2215, is a potent FLT3/AXL inhibitor, which showed potent antileukemic activity against AML with either or both FLT3-ITD and FLT3-D835 mutations. In invitro, among the 78 tyrosine kinases tested, ASP2215 inhibited FLT3, LTK, ALK, and AXL kinases by over 50% at 1 nM with an IC50 value of 0.29 nM for FLT3, approximately 800-fold more potent than for c-KIT, the inhibition of which is linked to a potential risk of myelosuppression. ASP2215 inhibited the growth of MV4-11 cells, which harbor FLT3-ITD, with an IC50 value of 0.92 nM, accompanied with inhibition of pFLT3, pAKT, pSTAT5, pERK, and pS6. ASP2215 decreased tumor burden in bone marrow and prolonged the survival of mice intravenously transplanted with MV4-11 cells. ASP2215 may have potential use in treating AML.
Ordering Information
Catalog Number Size Price Stock Quantity
B0084-462531 100 mg $499 In stock
B0084-462531 500 mg $1499 In stock
Bulk Inquiry
Appearance:
Solid powder
Synonyms:
Gilteritinib; ASP2215; ASP-2215; ASP 2215.
MSDS:
Inquire
InChIKey:
GYQYAJJFPNQOOW-UHFFFAOYSA-N
InChI:
InChI=1S/C29H44N8O3/c1-4-23-28(31-20-9-17-40-18-10-20)34-29(26(33-23)27(30)38)32-21-5-6-24(25(19-21)39-3)37-11-7-22(8-12-37)36-15-13-35(2)14-16-36/h5-6,19-20,22H,4,7-18H2,1-3H3,(H2,30,38)(H2,31,32,34)
Canonical SMILES:
CCC1=NC(=C(N=C1NC2CCOCC2)NC3=CC(=C(C=C3)N4CCC(CC4)N5CCN(CC5)C)OC)C(=O)N
Current Developer:
Astellas Pharma / Kotobuki Pharmaceutical Co., Ltd.
1.Combined effect of cabozantinib and gefitinib in crizotinib-resistant lung tumors harboring ROS1 fusions.
Kato Y;Ninomiya K;Ohashi K;Tomida S;Makimoto G;Watanabe H;Kudo K;Matsumoto S;Umemura S;Goto K;Ichihara E;Ninomiya T;Kubo T;Sato A;Hotta K;Tabata M;Toyooka S;Maeda Y;Kiura K Cancer Sci. 2018 Jul 27. doi: 10.1111/cas.13752. [Epub ahead of print]
The ROS1 tyrosine kinase inhibitor (TKI) crizotinib has shown dramatic effects in patients with non-small cell lung cancer (NSCLC) harboring ROS1 fusion genes. However, patients inevitably develop resistance to this agent. Therefore, a new treatment strategy is required for lung tumors with ROS1 fusion genes. Two lung cancer cell lines, HCC78 harboring SLC34A2-ROS1 and ABC-20 harboring CD74-ROS1, were used as cell line-based resistance models. Crizotinib-resistant HCC78R cells were established from HCC78. We comprehensively screened the resistant cells using a phosphor-receptor tyrosine kinase array and RNA sequence analysis by next-generation sequencing (NGS). HCC78R cells showed upregulation of HB-EGF and activation of EGFR phosphorylation and the EGFR signaling pathway. Recombinant HB-EGF or EGF rendered HCC78 cells or ABC-20 cells resistant to crizotinib. RNA sequence analysis by NGS revealed the upregulation of AXL in HCC78R cells. HCC78R cells showed marked sensitivity to EGFR-TKIs or anti-EGFR antibody treatment in vitro. Combinations of an AXL-inhibitor, cabozantinib or gilteritinib, and an EGFR-TKI were more effective against HCC78R cells than monotherapy with an EGFR-TKI or AXL inhibitor.
2.Clinical Profile of Gilteritinib in Japanese Patients with Relapsed/Refractory AML: an Open-Label Phase 1 Study.
Usuki K;Sakura T;Kobayashi Y;Miyamoto T;Iida H;Morita S;Bahceci E;Kaneko M;Kusano M;Yamada S;Takeshita S;Miyawaki S;Naoe T Cancer Sci. 2018 Jul 24. doi: 10.1111/cas.13749. [Epub ahead of print]
Gilteritinib, a novel, highly specific, potent fms-like tyrosine kinase 3/AXL inhibitor, demonstrated antileukemic activity in patients with relapsed/refractory acute myeloid leukemia. In this open-label, Phase 1 study (;NCT02181660;), Japanese patients (aged ≥18 years) with relapsed/refractory acute myeloid leukemia received once-daily gilteritinib escalating from 20 mg/day to 300 mg/day. Primary endpoints were safety/tolerability including the maximum tolerated dose and recommended dose; secondary endpoints were antileukemic activity and pharmacokinetics. Twenty-four Japanese patients with relapsed/refractory acute myeloid leukemia received once-daily oral gilteritinib in one of six dose-escalation cohorts (20, 40, 80, 120, 200, 300 mg/day). Gilteritinib was well tolerated. The maximum tolerated dose was 200 mg/day; dose-limiting toxicities were grade 3 tumor lysis syndrome (120 mg/day; n=1); and grade 3 elevated blood lactate dehydrogenase, amylase, blood creatine phosphokinase levels and syncope (all n=2; 300 mg/day). The recommended dose was 120 mg/day. The most common drug-related grade ≥3 adverse events were thrombocytopenia (n=4 [16.7%]) and increased blood creatine phosphokinase (n=3 [12.
3.Inhibition of FLT3 in AML: a focus on sorafenib.
Antar A;Otrock ZK;El-Cheikh J;Kharfan-Dabaja MA;Battipaglia G;Mahfouz R;Mohty M;Bazarbachi A Bone Marrow Transplant. 2017 Mar;52(3):344-351. doi: 10.1038/bmt.2016.251. Epub 2016 Oct 24.
FMS-like tyrosine kinase 3 (FLT3) is one of the most commonly mutated genes in AML. FLT3 is mutated in ~30% of patients with AML, either by internal tandem duplications (FLT3-ITD) of the juxta-membrane domain or by a point mutation, usually involving the tyrosine kinase domain. Several FLT3 tyrosine kinase inhibitors are being evaluated in multiple studies aiming at improving outcomes. The most widely used is sorafenib, a potent multikinase inhibitor approved for hepatocellular carcinoma and renal cell carcinoma. Sorafenib monotherapy or in combination with conventional chemotherapy, has been evaluated in various settings in AML, including front-line, relapsed or refractory disease including post-allograft failures and, more recently, as post-transplant maintenance therapy. Encouraging data have emerged with several other agents like lestaurtinib, midostaurin, crenolanib, gilteritinib and quizartinib. Although transient responses to FLT3 inhibitors are often observed in case of disease relapse, the most promising approach is the use of FLT3 inhibitors either in combination with induction chemotherapy or as consolidation/maintenance therapy after allogeneic hematopoietic cell transplantation.
Molecular Weight Calculator Molarity Calculator Solution Dilution Calculator

Related FLT3 Products


CAS 1055412-47-9 SU 5614

SU 5614
(CAS: 1055412-47-9)

SU4984 is a FLT3 inhibitor that induces growth arrest, apoptosis, and cell cycle arrest in Ba/F3 and AML cell lines expressing a constitutively activated FLT3. ...

CAS 301305-73-7 TCS-359

TCS-359
(CAS: 301305-73-7)

TCS-359 is a potent inhibitor of FLT3 with IC50 of 42 nM.

CAS 1839150-56-9 CHMFL-FLT3-122

CHMFL-FLT3-122
(CAS: 1839150-56-9)

CHMFL-FLT3-122 is a potent and selective FLT3 inhibitor (IC50 = 40 nM) with >10-fold and 170-fold selectivity for FLT3 over BTK kinase and c-KIT kinase. It caus...

CAS 1457983-28-6 G-749

G-749
(CAS: 1457983-28-6)

G-749 potently inhibits autophosphorylation of FLT3 with IC50 of ≤8 nM. In leukemia cells, G-749 shows antiproliferative activity by inducing apoptosis.

CAS 950769-58-1 Quizartinib

Quizartinib
(CAS: 950769-58-1)

This active molecular also known as AC220 and AC010220, is developed as a new second-generation FLT3 inhibitor for Flt3(ITD/WT) with IC50 of 1.1 nM/4.2 nM, ten ...

CAS 1254053-43-4 Gilteritinib

Gilteritinib
(CAS: 1254053-43-4)

Gilteritinib, also known as (ASP2215, is a potent FLT3/AXL inhibitor, which showed potent antileukemic activity against AML with either or both FLT3-ITD and FLT...

UNC-2025 hydrochloride

UNC-2025 hydrochloride is the hydrochloride salt of UNC-2025, which is the Mer/FLT3 dual inhibitor.

CAS 630124-46-8 AST 487

AST 487
(CAS: 630124-46-8)

AST487 is a Ret kinase inhibitor/FLT3 inhibitor, which displays high selectivity and potency toward FLT3 as a molecular target, and which could potentially be u...

CAS 1000669-72-6 KW-2449

KW-2449
(CAS: 1000669-72-6)

KW-2449 is a novel multikinase inhibitor, which suppresses the growth of leukemia cells with FLT3 mutations or T315I-mutated BCR/ABL translocation. Recent resea...

CAS 1204918-72-8 SB1317

SB1317
(CAS: 1204918-72-8)

SB1317 is a novel small molecule potent CDK/JAK2/FLT3 inhibitor. It dose-dependently inhibits signaling pathways downstream of CDKs, JAK2 and FLT3 in cancer cel...

CAS 1132827-21-4 AC 220 dihydrochloride

AC 220 dihydrochloride
(CAS: 1132827-21-4)

AC 220 dihydrochloride is a potent and selective inhibitor of FMS-like tyrosine kinase-3 (FLT3) used for the treatment of AML.

CAS 861214-33-7 5'-Fluoroindirubinoxime

5'-Fluoroindirubinoxime
(CAS: 861214-33-7)

5'-Fluoroindirubinoxime is an inhibitor of FMS-like receptor tyrosine kinase-3 (FLT3) (IC50 = 15 nM) with antiproliferative activity. It displays selectivity fo...

CAS 1429881-91-3 UNC-2025

UNC-2025
(CAS: 1429881-91-3)

UNC-2025 is a novel potent and highly orally bioavailable Mer/FLT3 dual inhibitor, capable of inhibiting Mer phosphorylation in vivo, following oral dosing as d...

CAS 387867-13-2 Tandutinib

Tandutinib
(CAS: 387867-13-2)

Tandutinib, also known as MLN 518, is a piperazinyl quinazoline receptor tyrosine kinase inhibitor with antineoplastic activity. Tandutinib inhibits the autopho...

FLT3-IN-1
(CAS: 1370256-78-2)

FLT3-IN-1, a Flt3 inhibitor, has been found to have week activity against T lymphoma Jurkat cells and human lung cancer PC-9 and H292 cells. IC50: 10 nM (in vit...

CAS 326914-10-7 SU11652

SU11652
(CAS: 326914-10-7)

SU11652 is a cell-permeable and sunitinib-like inhibitor of tyrosine kinase receptor (RTK) and angiogenesis with antineoplastic property. It selectively inhibit...

CAS 1327167-19-0 BPR1J-097

BPR1J-097
(CAS: 1327167-19-0)

BPR1J-097 is a novel potent FLT3 inhibitor with an IC50 of 11 nM.

Chemical Structure

CAS 1254053-43-4 Gilteritinib

Quick Inquiry

Verification code

Featured Items