KW-2449

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/ABL/ABL-T315I/Aurora A/Aurora B 的多激酶抑制剂，IC50 分别为 6.6/14/4/48/48 nM。

A multikinase inhibitor of FLT3/ABL/ABL-T315I/Aurora A/Aurora B with IC50 of 6.6/14/4/48/48 nM respectively; has little effect on PDGFRβ, IGF-1R, EGFR, and various serine/threonine kinases at 1 uM; exhibits potent growth inhibitory effects on leukemia cells with FLT3 mutations, resulting in the down-regulation of phosphorylated-FLT3/STAT5, G1 arrest, and apoptosis; orally active.(In Vitro):KW-2449 shows growth inhibitory activities against FLT3/ITD-, FLT3/D835Y-, and wt-FLT3/FL-expressing 32D cells, MOLM-13 and MV4;11 with GI50 values of 0.024, 0.046, 0.014, 0.024, and 0.011 μM, respectively. KW-2449 suppresses the phosphorylations of FLT3 (P-FLT3) and its downstream molecule phospho-STAT5 (P-STAT5) in MOLM-13 cells in a dose-dependent manner. KW-2449 increases the percentage of cells in the G1 phase of the cell cycle and reciprocally reduced the percentage of cells in the S phase, resulting in the increase of apoptotic cell population.(In Vivo):Oral administration of KW-2449 shows dose-dependent and significant tumor growth inhibition in FLT3-mutated xenograft model with minimum bone marrow suppression. In FLT3 wild-type human leukemia, it induces the reduction of phosphorylated histone H3, G2/M arrest, and apoptosis. In imatinib-resistant leukemia, KW-2449 contributes to release of the resistance by the simultaneous down-regulation of BCR/ABL and Aurora kinases. Furthermore, the antiproliferative activity of KW-2449 is confirmed in primary samples from AML and imatinib-resistant patients. The inhibitory activity of KW-2449 is not affected by the presence of human plasma protein, such as α1-acid glycoprotein.

KW-2449 shows growth inhibitory activities against FLT3/ITD-, FLT3/D835Y-, and wt-FLT3/FL-expressing 32D cells, MOLM-13 and MV4;11 with GI50 values of 0.024, 0.046, 0.014, 0.024, and 0.011 μM, respectively. KW-2449 suppresses the phosphorylations of FLT3 (P-FLT3) and its downstream molecule phospho-STAT5 (P-STAT5) in MOLM-13 cells in a dose-dependent manner. KW-2449 increases the percentage of cells in the G1 phase of the cell cycle and reciprocally reduced the percentage of cells in the S phase, resulting in the increase of apoptotic cell population.

Oral administration of KW-2449 shows dose-dependent and significant tumor growth inhibition in FLT3-mutated xenograft model with minimum bone marrow suppression. In FLT3 wild-type human leukemia, it induces the reduction of phosphorylated histone H3, G2/M arrest, and apoptosis. In imatinib-resistant leukemia, KW-2449 contributes to release of the resistance by the simultaneous down-regulation of BCR/ABL and Aurora kinases. Furthermore, the antiproliferative activity of KW-2449 is confirmed in primary samples from AML and imatinib-resistant patients. The inhibitory activity of KW-2449 is not affected by the presence of human plasma protein, such as α1-acid glycoprotein.

KW 2449 | KW2449

Tyrosine Kinase

FLT3

Abl|Abl(T315I)|AuroraA|FGFR1|FLT3|FLT3(D835Y)|JAK2|Kit|Src

Cancer

Blood cancer

1000669-72-6

332.399

C20H20N4O

>98% (HPLC)

10 mM in DMSO

O=C(C1=CC=C(/C=C/C2=NNC3=C2C=CC=C3)C=C1)N4CCNCC4

Methanone, [4-[2-(1H-indazol-3-yl)ethenyl]phenyl]-1-piperazinyl-

(-20℃)

With Ice Pack

≥ 2 years