FLT3-IN-3

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-IN-3是一种有效的FLT3抑制剂，FLT3 WT和FLT3 D835Y的IC50分别为13和8 nM。

FLT3-IN-3 is an effective FLT3 inhibitor, and the IC50s of FLT3 WT and FLT3 D835Y are 13 and 8 nM, respectively.

FLT3-IN-3 (Compound 7d) inhibits the proliferation of FLT3-ITD positive MV4-11 and MOLM-13 cell lines very effectively at low nanomolar concentrations (GI50 values 2 and 1 nM, respectively).FLT3-IN-3 (1 nM, 10nM, 100 nM, 1 μM and 10 μM; 72 hours) inhibits the Ba/F3 FLT3-ITD cells with the GI50 of 0.034±0.015 μM, and inhibits the parental Ba/F3 cells with the GI50 value of 1.136±0.389 μM. Concentrations as low as 1 nM are sufficient to block the autophosphorylation of the FLT3 receptor tyrosine kinase at three different tyrosine residues (589, 591, and 842). Moreover, this inhibition suppresses phosphorylation of several downstream targets of FLT3. Notably, FLT3-IN-3 (0.01, 0.1, 1, 10 and 100 nM; 1 hours) abolishes phosphorylation of STAT5 at Y694, which is a direct substrate of the oncogenic FLT3-ITD variant. The second pathway affected is the MAPK cascade: Two key components of this signaling pathway, ERK1/2 (T202/Y204) and MEK1/2 (S217/221), exhibit reduced phosphorylation upon treatment with FLT3-IN-3. FLT3-IN-3 also interfers with PI3K/AKT pathway which is confirmed by reduced phosphorylation of AKT at S473. Cell Proliferation AssayCell Line:Murine Ba/F3 FLT3-ITD and parental Ba/F3 cells Concentration:1 nM, 10nM, 100 nM, 1 μM and 10 μM Incubation Time:72 hours Result:The GI50s for Ba/F3 FLT3-ITD cells and parental Ba/F3 cells are 0.034±0.015 μM and 1.136±0.389 μM, respectively.Western Blot Analysis Cell Line:MV4-11 cells Concentration:0.01, 0.1, 1, 10 and 100 nM Incubation Time:1 hours Result:Concentrations as low as 1 nM were sufficient to block the autophosphorylation of the FLT3 receptor tyrosine kinase at three different tyrosine residues (589, 591, and 842).

A single dose of FLT3-IN-3 (Compound 7d; 10 mg/kg; i.p.) in mice with subcutaneous MV4-11 xenografts causes sustained inhibition of FLT3 and STAT5 phosphorylation over 48 hours. Animal Model:Female athymic nu/nu mice with subcutaneously implanted MV4-11 xenografts Dosage:10 mg/kg Administration:Intraperitoneal (i.p.) injection; 48 hours Result:Effectively inhibited FLT3-ITD autophosphorylation in MV4-11 xenografts.

——

Angiogenesis

FLT

FLT3 (D835Y)|FLT3 (WT)

——

——

2229050-90-0

490.64

C27H38N8O

>98% (HPLC)

DMSO:250 mg/mL (509.54 mM; Need ultrasonic)

N[C@H](CC1)CC[C@@H]1NC2=NC3=C(N=CN3C4CCCC4)C(NC5=CC=C(CN6CCOCC6)C=C5)=N2

——

(-20℃)

With Ice Pack

≥ 2 years