 Chemical Structure.png)
Physicochemical Properties
| Molecular Formula | C25H17F4N5O2 |
| Molecular Weight | 495.43 |
| Exact Mass | 495.131 |
| CAS # | 1616428-23-9 |
| PubChem CID | 118480924 |
| Appearance | Light yellow to yellow solid powder |
| Density | 1.5±0.1 g/cm3 |
| Boiling Point | 663.8±55.0 °C at 760 mmHg |
| Flash Point | 355.3±31.5 °C |
| Vapour Pressure | 0.0±2.0 mmHg at 25°C |
| Index of Refraction | 1.674 |
| LogP | 4.44 |
| Hydrogen Bond Donor Count | 4 |
| Hydrogen Bond Acceptor Count | 7 |
| Rotatable Bond Count | 4 |
| Heavy Atom Count | 36 |
| Complexity | 811 |
| Defined Atom Stereocenter Count | 0 |
| InChi Key | MWHHJYUHCZWSLS-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C25H17F4N5O2/c1-11-9-30-23(32-11)16-5-4-14(17-10-31-24(35)21(16)17)15-3-2-13(8-18(15)27)33-25(36)34-22-19(28)6-12(26)7-20(22)29/h2-9H,10H2,1H3,(H,30,32)(H,31,35)(H2,33,34,36) |
| Chemical Name | 1-[3-fluoro-4-[7-(5-methyl-1H-imidazol-2-yl)-1-oxo-2,3-dihydroisoindol-4-yl]phenyl]-3-(2,4,6-trifluorophenyl)urea |
| HS Tariff Code | 2934.99.9001 |
| 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) |
Biological Activity
| Targets | Pan-FLT3/Pan-BTK[1] |
| ln Vitro | Luxeptinib suppresses cell growth with an IC50 of 32 nM (MEC-1 CLL cells; 0.1~10 μM; 72 hours)[1]. In primary chronic lymphocytic leukemia (CLL) cells, luxeptinib phosphorylates S6 ribosomal protein, ERK1/2, BTK, PLCg2, AKT, and SYK, and it also substantially inhibits SYK phosphorylation [1]. The phosphorylation of FLT3 and STAT5 is entirely inhibited by luxeptinib (MV4-11 cells; 500 pM; 1 hour) [2]. |
| Cell Assay |
Cell Proliferation Assay[1] Cell Types: MEC-1 CLL cells Tested Concentrations: 0.1~10 µM Incubation Duration: 72 hrs (hours) Experimental Results: Inhibited cells proliferation with an IC50 of 32 nM. |
| References |
[1]. CG-806, a First-in-Class Pan-FLT3/Pan-BTK Inhibitor, Exhibits Broad Signaling Inhibition in Chronic Lymphocytic Leukemia Cells. bloodjournal Blood blood (2019). 134 (Supplement_1) : 3051. [2]. Abstract 44: CG′806, a first-in-class FLT3/BTK inhibitor, exhibits potent activity against AML patient samples with mutant or wild type FLT3, as well as other hematologic malignancy subtypes. [3]. CG '806, a Novel Pan-FLT3/BTK Multi-Kinase Inhibitor, Induces Cell Cycle Arrest, Apoptosis or Autophagy in AML Cells Depending on FLT3 Mutation Status. Blood blood (2017).130 (Suppl_1) : 462. [4]. Aptose Biosciences to Present CG’806 Data at AACR Hematologic Malignancies Meeting. |
| Additional Infomation | Luxeptinib is an orally bioavailable reversible, pan-inhibitor of both FMS-like tyrosine kinase 3 (FLT3; CD135; STK1; FLK2) and Bruton's tyrosine kinase (BTK; Bruton agammaglobulinemia tyrosine kinase), with potential antineoplastic activity. Upon oral administration, luxeptinib targets, non-covalently binds to and inhibits the activity of both FLT3, including both wild-type (WT) FLT3 and FLT3-ITD (internal tandem duplications), tyrosine kinase domain (FLT3-TKD), and gatekeeper (FLT3-F691L) mutant forms, and BTK, including both the WT and its C481S mutant (BTK-C481S) form. This inhibits both uncontrolled FLT3-mediated and B-cell antigen receptor (BCR)-mediated signaling, respectively. This results in the inhibition of proliferation in tumor cells overexpressing FLT3 and BTK. In addition, CG-806 also inhibits, to a lesser degree, other oncogenic kinases, such as MET, RET, discoidin domain-containing receptor 2 (DDR2), Aurora kinase A, and interleukin-2-inducible T-cell kinase (ITK). FLT3, a class III receptor tyrosine kinase (RTK), is overexpressed or mutated in most B-lineage neoplasms and in acute myeloid leukemias (AMLs), and plays a key role in tumor cell proliferation. BTK, a member of the Src-related BTK/Tec family of cytoplasmic tyrosine kinases essential to BCR signaling, is overexpressed or mutated in B-cell malignancies; it plays an important role in the development, activation, signaling, proliferation and survival of B-lymphocytes. |
Solubility Data
| Solubility (In Vitro) | DMSO : 50 mg/mL (100.92 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (5.05 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication. 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 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (4.20 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 20.8 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 3: ≥ 2.08 mg/mL (4.20 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 20.8 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 | 2.0184 mL | 10.0922 mL | 20.1845 mL | |
| 5 mM | 0.4037 mL | 2.0184 mL | 4.0369 mL | |
| 10 mM | 0.2018 mL | 1.0092 mL | 2.0184 mL |