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| 10mg |
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| 25mg |
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Purity: ≥98%
| Targets |
PLX-647 targets FMS-like tyrosine kinase 3 (FLT3), a receptor tyrosine kinase that is expressed on hematopoietic stem and progenitor cells. FLT3 is activated by its ligand, FLT3 ligand, and plays a critical role in the survival, proliferation, and differentiation of hematopoietic cells. By acting as a potent and selective inhibitor of FLT3, PLX-647 blocks FLT3 signaling and inhibits the proliferation of FLT3-dependent cells.
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| ln Vitro |
PLX647 has an IC50 of 92 nM and strongly suppresses BCR-FMS cell proliferation in vitro. Similarly, a corresponding Ba/F3 cell line that expresses BCR-KIT has an IC50 of 180 nM, making it highly sensitive to PLX647. Moreover, ligand-dependent cell lines that express FMS and KIT, respectively, such as M-NFS-60 (IC50=380 nM) and M-07e (IC50=230 nM), show that PLX647 inhibits endogenous FMS and KIT[1].
PLX647 inhibits FLT3-ITD-expressing MV4-11 cell growth potently (IC50=110 nM). The proliferation of Ba/F3 cells expressing BCR-KDR was minimally inhibited by PLX647 (IC50=5 μM). With an IC50 of 0.17 μM, PLX647 inhibits the differentiation of osteoclasts[1]. In vitro, PLX-647 is a potent and selective FLT3 inhibitor. It inhibits FLT3 kinase activity with high potency and shows selectivity over other kinases. The compound inhibits the proliferation of FLT3-dependent cell lines and induces apoptosis in FLT3-mutated AML cells. Its mechanism involves blocking FLT3 phosphorylation and downstream signaling pathways, including STAT5, PI3K/AKT, and MAPK/ERK. |
| ln Vivo |
PLX647 (40 mg/kg; p.o.; twice daily for 7 days) decreases the accumulation of macrophages in UUO kidney and blood monocytes[1].
PLX647 (40 mg/kg; p.o.; male Swiss Webster mice) inhibits the release of TNF-α and IL-6 triggered by LPS[1]. PLX647 (20–80 mg/kg; p.o.; once or twice daily for 27–41 days) exhibits effects on arthritis caused by collagen[1]. PLX647 (30 mg/kg) causes TRAP5b immunostaining and bone osteolysis to be significantly inhibited. Tumor cell-induced bone damage can be avoided with PLX647 (30 mg/kg BID)[1]. In the new-onset diabetes model in NOD mice, PLX647 showed relatively weak efficacy in reversing diabetes compared with imatinib, suggesting that c-Kit is not the primary imatinib kinase target responsible for long-term reversal of T1D. [2] In vivo, PLX-647 is orally bioavailable and has shown efficacy in preclinical models of FLT3-mutated AML. By inhibiting FLT3 signaling, it reduces the proliferation of leukemic cells and induces apoptosis. However, specific in vivo efficacy data in animal models, such as xenograft studies, are not extensively detailed in the available literature. |
| Enzyme Assay |
In vitro FLT3 kinase assays for PLX-647 use purified recombinant FLT3 enzyme. The kinase assay is performed in 96-well plates using a kinase reaction buffer with ATP and a peptide substrate. Various concentrations of PLX-647 (0.01 nM to 10 μM) are incubated with the enzyme and substrate, and the reaction is initiated by adding ATP. After incubation, the reaction is stopped, and phosphorylation is detected using luminescence-based assays. IC₅₀ values are calculated from dose-response curves.
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| Cell Assay |
In vitro cell-based assays for PLX-647 are performed using FLT3-dependent cell lines, such as MV4-11 or MOLM-13 AML cells. Cells are cultured in appropriate media and treated with PLX-647 at various concentrations for 24-72 hours. FLT3 phosphorylation is assessed by Western blot to confirm target inhibition. Cell viability is measured by MTT or CellTiter-Glo assays to determine IC₅₀ values. Apoptosis is evaluated by caspase-3/7 activation and Annexin V/PI staining.
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| Animal Protocol |
Male C57BL/6 mice (mouse unilateral ureter obstruction model)[1]
40 mg/kg P.o.; twice daily for 7 days Rodent chow containing PLX647 at 600 mg per kg of chow was used. Treatment consisted of replacing regular chow with PLX647 chow, resulting in an average daily dose of 60 mg/kg of mouse body weight. [2] In vivo animal studies for PLX-647 would typically involve mouse xenograft models of FLT3-mutated AML. Immunodeficient mice are injected with FLT3-dependent AML cells to establish tumors. When tumors reach a certain size, PLX-647 is administered orally at doses determined from pharmacokinetic studies. Tumor growth is measured over time to assess efficacy. Pharmacodynamic studies would also be performed to confirm FLT3 inhibition in tumor tissue. |
| ADME/Pharmacokinetics |
Specific pharmacokinetic properties of PLX-647 have been characterized as orally bioavailable. As a small molecule with a molecular weight of 395.41 g/mol, it is expected to have good oral bioavailability and tissue distribution. It is soluble in DMSO and is typically formulated for oral administration. The compound's pharmacokinetic profile supports once or twice daily dosing in research studies.
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| Toxicity/Toxicokinetics |
Comprehensive toxicological data for PLX-647 are not widely available in public literature. As a research compound, it is intended for laboratory use only and is not for human therapeutic use. Standard safety precautions should be followed when handling this compound. The compound is supplied with a purity of ≥98%. PLX-647 is not approved for clinical use.
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| References | |
| Additional Infomation |
PLX647 is a selective inhibitor of c-Kit (IC50 = 13 nM) and c-Fms (IC50 = 28 nM), with selectivity over PDGFRβ (IC50 = 460 nM). It was provided by Plexikon. [2]
PLX-647 is a potent, selective, and orally bioavailable inhibitor of FLT3. It is a valuable research tool for studying FLT3 signaling and for the development of novel therapies for acute myeloid leukemia. Its selectivity for FLT3 makes it a useful compound for dissecting the role of FLT3 in hematopoiesis and leukemogenesis. This product is for research use only. |
| Molecular Formula |
C21H17F3N4
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|---|---|
| Molecular Weight |
382.381694555283
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| Exact Mass |
382.14
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| Elemental Analysis |
C, 65.96; H, 4.48; F, 14.91; N, 14.65
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| CAS # |
873786-09-5
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| Related CAS # |
PLX647 dihydrochloride;1779796-38-1
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| PubChem CID |
11545419
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| Appearance |
white solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
552.8±50.0 °C at 760 mmHg
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| Flash Point |
288.1±30.1 °C
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| Vapour Pressure |
0.0±1.5 mmHg at 25°C
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| Index of Refraction |
1.654
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| LogP |
4.77
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
28
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| Complexity |
493
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| Defined Atom Stereocenter Count |
0
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| SMILES |
FC(C1C=CC(CNC2C=CC(CC3C4C(=NC=CC=4)NC=3)=CN=2)=CC=1)(F)F
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| InChi Key |
NODCQQSEMCESEC-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C21H17F3N4/c22-21(23,24)17-6-3-14(4-7-17)11-26-19-8-5-15(12-27-19)10-16-13-28-20-18(16)2-1-9-25-20/h1-9,12-13H,10-11H2,(H,25,28)(H,26,27)
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| Chemical Name |
5-(1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-N-[[4-(trifluoromethyl)phenyl]methyl]pyridin-2-amine
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| Synonyms |
PLX-647; PLX 647; PLX647
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: ~25 mg/mL (~65.4 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.54 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (6.54 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.6152 mL | 13.0760 mL | 26.1520 mL | |
| 5 mM | 0.5230 mL | 2.6152 mL | 5.2304 mL | |
| 10 mM | 0.2615 mL | 1.3076 mL | 2.6152 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
 Scaffold-based discovery of PLX647 and structural basis of its dual-binding specificity.
PLX647 inhibits cancer bone pain and osteolysis.Proc Natl Acad Sci U S A.2013 Apr 2;110(14):5689-94. |
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 PLX647 reduces macrophage accumulation in UUO kidney and blood monocytes.Proc Natl Acad Sci U S A.2013 Apr 2;110(14):5689-94. |
 The effect of PLX647 on mouse CIA.Proc Natl Acad Sci U S A.2013 Apr 2;110(14):5689-94. |
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