Tandutinib

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

FLT3、Kit 和 PDGFR 的有效抑制剂，IC50 分别为 0.22、0.17 和 0.2 uM。

A potent inhibitor of FLT3, Kit and PDGFR with IC50 of 0.22, 0.17 and 0.2 uM, respectively; displays 15-20-fold less potent activity against CSF-1R; inhibits IL-3-independent cell growth and FLT3-ITD autophosphorylation with IC50 of 10-100 nM, induces apoptosis and inhibits FLT3-ITD phosphorylation, cellular proliferation and signaling through MAPK and PI3K pathways; exhibits ativity in murine models of FLT3-ITD-mediated disease.Brain Cancer Phase 2 Discontinued(In Vitro):Tandutinib (0-3 μM; 30 minutes; Ba/F3 cells) treatment inhibits IL-3-independent cell growth and FLT3-ITD autophosphorylation with an IC50 of 10-100 nM in Ba/F3 cells expressing different FLT3-ITD mutants.Tandutinib (1 μM; 24-96 hours; Molm-14 and THP-1 AML cells) treatment induces apoptosis in FLT3-ITD-positive AML cells.In human FLT3-ITD-positive AML cell lines, Tandutinib inhibits FLT3-ITD phosphorylation (IC50 of ~30 nM). As with Erk2, a constitutively high level of Akt phosphorylation is readily detected and is efficiently blocked by pretreatment of the Molm-14 cells with 100-300 nM Tandutinib.Tandutinib inhibits cell proliferation of the FLT3-ITD-positive Molm-13 and Molm-14 with an IC50 of 10 nM. And signaling through the MAP kinase and PI3 kinase pathways.(In Vivo):Tandutinib (60 mg/kg; oral gavage; daily; for 35 days; athymic nude mice) treatment causes a statistically significant increase in survival that was extended on average by 20 days.

Tandutinib (0-3 μM; 30 minutes; Ba/F3 cells) treatment inhibits IL-3-independent cell growth and FLT3-ITD autophosphorylation with an IC50 of 10-100 nM in Ba/F3 cells expressing different FLT3-ITD mutants.Tandutinib (1 μM; 24-96 hours; Molm-14 and THP-1 AML cells) treatment induces apoptosis in FLT3-ITD-positive AML cells.In human FLT3-ITD-positive AML cell lines, Tandutinib inhibits FLT3-ITD phosphorylation (IC50 of ~30 nM). As with Erk2, a constitutively high level of Akt phosphorylation is readily detected and is efficiently blocked by pretreatment of the Molm-14 cells with 100-300 nM Tandutinib.Tandutinib inhibits cell proliferation of the FLT3-ITD-positive Molm-13 and Molm-14 with an IC50 of 10 nM. And signaling through the MAP kinase and PI3 kinase pathways. Apoptosis Analysis Cell Line:Molm-14 and THP-1 AML cells Concentration:1 μM Incubation Time:24 hours, 48 hours, 72 hours, 96 hours Result:Induced apoptosis in FLT3-ITD-positive AML cells.Western Blot Analysis Cell Line:Ba/F3 cells Concentration:0 μM, 0.003 μM, 0.01 μM, 0.03 μM, 0.1 μM, 1 μM and 3 μM Incubation Time:30 minutes Result:In Ba/F3 cells expressing different FLT3-ITD mutants, inhibited IL-3-independent cell growth and FLT3-ITD autophosphorylation.

Tandutinib (60 mg/kg; oral gavage; daily; for 35 days; athymic nude mice) treatment causes a statistically significant increase in survival that was extended on average by 20 days. Animal Model:Athymic nude mice injected with Ba/F3 cells Dosage:60 mg/kg Administration:Oral gavage; daily; for 35 days Result:Caused a statistically significant increase in survival that was extended on average by 20 days.

MLN-518 | MLN518 | CT53518 | MLN0518 | MLN-0518 | CT-53518

Tyrosine Kinase

FLT3

c-Kit|CSF-1R|FLT3|PDGFRβ|Src

Cancer

Brain Cancer

387867-13-2

562.703

C31H42N6O4

>98% (HPLC)

DMSO: ≥ 36 mg/mL

O=C(N1CCN(C2=C3C=C(OC)C(OCCCN4CCCCC4)=CC3=NC=N2)CC1)NC5=CC=C(OC(C)C)C=C5

1-Piperazinecarboxamide, 4-[6-methoxy-7-[3-(1-piperidinyl)propoxy]-4-quinazolinyl]-N-[4-(1-methylethoxy)phenyl]-

(-20℃)

With Ice Pack

≥ 2 years