| Hazard Information | Back Directory | [Description]
TTT-3002 is a tyrosine kinase inhibitor (TKI) that is one of the most potent FLT3 inhibitors discovered to date. Studies using human FLT3/ITD mutant leukemia cell lines revealed the half maximal inhibitory concentration (IC50) for inhibiting FLT3 autophosphorylation is from 100 to 250 pM. The proliferation IC50 for TTT-3002 in these same cells was from 490 to 920 pM. TTT-3002 also showed potent activity when tested against the most frequently occurring FLT3-activating point mutation, FLT3/D835Y, against which many current TKIs are ineffective. | [Uses]
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]. | [in vivo]
TTT 3002 (6 mg/kg, Oral gavage, twice per day, for 2 to 4 weeks) is effective in vivo in several mouse tumor models of FLT3/ITD-associated AML (acute myeloid leukemia) with minimal toxicity[1].
TTT 3002 (6 mg/kg, Oral gavage, single) is rapidly absorbed with a biphasic maximum serum concentration (Cmax) followed by a monoexponential decay[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. |
| [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 DOI:10.1182/blood-2013-08-523035 |
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