| Description |
TTT 3002 is a potent and orally active FLT3 inhibitor. TTT 3002 potently inhibits FLT3 phosphorylation by activating mutations at residue D835, with an IC50 of 0.2 nM. TTT 3002 can be used for AML (acute myeloid leukemia) research[1].
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| Related Catalog |
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| In Vitro |
TTT 3002 下调 Molm14 和 MV4-11 细胞中的 FLT3 磷酸化(pFLT3)[1]。 TTT 3002 诱导细胞周期停滞，随后显著诱导凋亡[1]。 Western Blot Analysis[1] Cell Line: Molm14 and MV4-11 cells Concentration: 0, 0.25, 0.5, 1, 2 nM Incubation Time: 1 h Result: Downregulated FLT3 phosphorylation (pFLT3) in Molm14 and MV4-11 cells in a dose-dependent manner. The IC50 for FLT3 phosphorylation in both cell lines was six- to seven fold lower for TTT 3002 compared with Quizartinib (HY-13001) at 0.2 vs 1.3 nM, respectively. Cell Cycle Analysis[1] Cell Line: Molm14 and MV4-11 cells Concentration: 0, 1, 2, 5, 10 nM Incubation Time: 24 h Result: Showed cell cycle arrest followed by marked induction of apoptosis, along with concurrent activation of caspase 3 and poly ADP ribose polymerase cleavage.
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| In Vivo |
TTT 3002 (6 mg/kg，口服灌胃，每天两次，持续 2 至 4 周) 在体内对几种 FLT3/ITD 相关 AML 小鼠肿瘤模型有效，且毒性极小[1]。 TTT 3002 (6 mg/kg，口服灌胃，单次) 可被迅速吸收，具有双相最大血清浓度 (Cmax) 随后是单指数衰减[1]。 Animal Model: BALB/C mice (female, age 6 to 8 weeks, received Ba/F3-ITD Luc+ cells by tail vein injection on day 0)[1] Dosage: 6 mg/kg Administration: Oral gavage, twice per day, for 2 to 4 weeks Result: Showed no significant changes in animal weight and was sufficient to eliminate the presence of Ba/F3-ITD Luc+ cells by day 17 (10 days of treatment). Animal Model: Leukemic engrafted mice (female, age 6 to 8 weeks)[1] Dosage: 6 mg/kg Administration: Oral gavage, single (Pharmacokinetic Analysis) Result: After oral administration, TTT 3002 was rapidly absorbed with a biphasic maximum serum concentration (Cmax) followed by a monoexponential decay. The Cmax and area under the concentration-time curve from time 0 to infinity (AUC0→∞) were 613 nM and 3127 nM⋅h, respectively. The half-life, apparent volume of distribution, and apparent clearance were 3.6 hours, 21 L/kg, and 4.1 L/h per kilogram, respectively.
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| References |
[1]. Ma H, et al. TTT-3002 is a novel FLT3 tyrosine kinase inhibitor with activity against FLT3-associated leukemias in vitro and in vivo. Blood. 2014 Mar 6;123(10):1525-34
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