Tandutinib (MLN518) is a potent, ATP-competitive and reversible inhibitor of Type III receptor tyrosine kinases (RTKs). In vitro, Tandutinib (MLN518) inhibits FLT3, c-KIT and PDGFRß with a median IC50 of approximately 30 nM. Tandutinib inhibited FLT3 phosphorylation, downstream signaling and malignant growth in vitro and in animal models. In cellular assays, Tandutinib inhibited the autophosphorylation of these receptors with an IC50 of approximately 200 nM. Tandutinib (MLN518) is quite selective; of the other receptor tyrosine kinases tested, only CSF-1R was inhibited to any appreciable degree. Based on Tandutinib's activity against the FLT3 receptor, Tandutinib was tested against a panel of clinically isolated FLT3 ITD gain of function mutants expressed in BaF3 cells. Both the W51 mutant and the WT FLT3 receptor showed a significant inhibition of receptor autophosphorylation with Tandutinib treatment. In studies of 5 different FLT3/ITD expressing cells, Tandutinib inhibited cell growth with an IC50 of 10-30 nM in all cases.
Cell Experiment | |
---|---|
Cell lines | AML cells expressing FLT3-ITD |
Preparation method | AML cell lines HL60 (AML-M3) and AML193 (AML-M5), KG-1, KG-1a, THP-1, and ALL cell line RS4;11 were purchased from ATCC (Bethesda, MD). Cells (initial count of 0.3* 105–1.0 *105) were washed three times in RPMI 1640 medium and plated in 1 ml of complete growth media (without IL-3 for the Ba/F3 cells) in the presence of increasing concentrations of CT53518 (0.004–30 μM). Cells were grown for 3–7 days in tissue culture, and viable cells, determined by Trypan blue dye exclusion, were counted. |
Concentrations | 0.004-30 μM |
Incubation time | 3 days |
Animal Experiment | |
---|---|
Animal models | Ba/F3 nude mouse model of FLT3-ITD-mediated leukemia |
Formulation | 0.5% methyl cellulose |
Dosages | 60 mg/kg BID day 7-57 |
Administration | oral gavage |
Molecular Weight | 562.7 |
Formula | C31H42N6O4 |
CAS Number | 387867-13-2 |
Solubility (25°C) | Ethanol |
Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
Species | Mouse | Rat | Rabbit | Guinea pig | Hamster | Dog |
Weight (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
Body Surface Area (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
Km factor | 3 | 6 | 12 | 8 | 5 | 20 |
Animal A (mg/kg) = Animal B (mg/kg) multiplied by | Animal B Km |
Animal A Km |
For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.
Related FLT3 Products |
---|
FLT3-IN-19
FLT3-IN-19 is a potent and selective FLT3 inhibitor with IC50 of 0.213 nM. |
LT-540-717
LT-540-717 is a potent FLT3 inhibitor (IC50=0.62 nM) with antiproliferative activity. |
GTP-14564
GTP-14564 is a tyrosine kinase inhibitor targeting to internal tandem duplication (ITD) and FLT3. |
HDAC-IN-63
HDAC-IN-63 is a dual FLT3/HDAC inhibitor (IC50: 0.844 and 30.0 nM for FLT3 and HDAC1 respectively). |
FLT3-IN-20
FLT3-IN-20 is a potent FLT3 inhibitor with IC50 values of 1 and 4 nM for FLT3-D835Y and FLT3-ITD, respectively. |
Products are for research use only. Not for human use. We do not sell to patients.
© Copyright 2010-2023 AbMole BioScience. All Rights Reserved.