| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| Other Sizes |
|
| ln Vitro |
In viability assays, XL228 exhibits a broad pattern of inhibition with protein inhibitors, such as the tyrosine inhibitors IGF1R, SRC, ABL, FGFR1-3, and ALK as well as the serine/threonine inhibitors Aurora A and Aurora B. Approximately 30% of cell lines with XL228 relationships show XL228 IC50 values <100 nM, including many cell lines with characteristic ALK or FGFR mutations or loss. Aurora A and B are phosphorylated by XL228 at a 10 nM concentration. HeLa cells treated for a brief period of time may experience disruption of the mitotic spindle; most mitotic cells show unipolar spindles and chromosomal disarray [2]. Low nanomolar biological activity is shown by Abl topology (Ki=5 nM) and the T315I version of Abl against imatinib and dasatinib (Ki= 1.4 nM). With an IC50 of 33 and 43 nM, respectively, XL228 suppresses the phosphorylation of BCR-ABL and its substrate STAT5 in K562 cells in vitro [3].
|
|---|---|
| ln Vivo |
In K562 xenograft tumors, XL228 has a strong effect on BCR-ABL signaling, according to single-dose pharmacodynamic tests. The phosphorylation of BCR-ABL was reduced by 50% at a dose of 3.5 μM and by 50% at a concentration of 0.8 μM of XL228 Manhattan; phosphorylated STAT5 also showed a comparable reduction [3].
|
| References |
|
| Additional Infomation |
XL228 is a novel anticancer compound designed to inhibit the insulin-like growth factor type-1 receptor (IGF1R), Src and Abl tyrosine kinases – targets that play crucial roles in cancer cell proliferation, survival and metastasis.
Tyrosine Kinase Inhibitor XL228 is a synthetic molecule that targets multiple tyrosine kinases with potential antineoplastic activity. Tyrosine kinase inhibitor XL228 binds to and inhibits the activities of multiple tyrosine kinases, such as the insulin-like growth factor 1 receptor (IGF1R), Src tyrosine kinase, and Bcr-Abl tyrosine kinase. Blockade of these kinases may result in the inhibition of tumor angiogenesis, cell proliferation, and metastasis. In addition, this agent may be a potent inhibitor of the T315I mutant form of the Abl protein, which is associated with the resistance of chronic myelogenous leukemia (CML) to other tyrosine kinase inhibitors. IGF1R and Src tyrosine kinases are upregulated in many tumor cells and play important roles in tumor cell proliferation and metastasis. Bcr-Abl translocation leads to constitutive activation of ABL kinase and is commonly associated with Philadelphia-positive acute lymphocytic leukemia (ALL). Drug Indication Investigated for use/treatment in leukemia (lymphoid) and leukemia (myeloid). Mechanism of Action XL228 potently inhibits the T315I mutant form of ABL, which is resistant to inhibition by other targeted therapies approved for chronic myelogenous leukemia. XL228 also targets IGF1R, which is a receptor tyrosine kinase that is highly expressed and activated in a broad range of human tumors and is thought to promote tumor growth, survival and resistance to chemotherapeutic agents. XL228 showed efficacy in a variety of solid tumor xenograft models. |
| Molecular Formula |
C22H31N9O
|
|---|---|
| Molecular Weight |
437.54
|
| Exact Mass |
437.265
|
| CAS # |
898280-07-4
|
| PubChem CID |
59757974
|
| Appearance |
White to off-white solid powder
|
| Density |
1.3±0.1 g/cm3
|
| Boiling Point |
715.7±70.0 °C at 760 mmHg
|
| Flash Point |
386.6±35.7 °C
|
| Vapour Pressure |
0.0±2.3 mmHg at 25°C
|
| Index of Refraction |
1.669
|
| LogP |
1.35
|
| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
9
|
| Rotatable Bond Count |
8
|
| Heavy Atom Count |
32
|
| Complexity |
598
|
| Defined Atom Stereocenter Count |
0
|
| InChi Key |
ALKJNCZNEOTEMP-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C22H31N9O/c1-14(2)17-10-16(32-29-17)13-23-22-25-19(24-20-11-18(27-28-20)15-4-5-15)12-21(26-22)31-8-6-30(3)7-9-31/h10-12,14-15H,4-9,13H2,1-3H3,(H3,23,24,25,26,27,28)
|
| Chemical Name |
4-N-(5-cyclopropyl-1H-pyrazol-3-yl)-6-(4-methylpiperazin-1-yl)-2-N-[(3-propan-2-yl-1,2-oxazol-5-yl)methyl]pyrimidine-2,4-diamine
|
| Synonyms |
XL 228; XL-228; XL228
|
| 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)
|
| Solubility (In Vitro) |
DMSO : ≥ 83.33 mg/mL (~190.45 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.75 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 2: ≥ 2.08 mg/mL (4.75 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 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. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (4.75 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2855 mL | 11.4275 mL | 22.8551 mL | |
| 5 mM | 0.4571 mL | 2.2855 mL | 4.5710 mL | |
| 10 mM | 0.2286 mL | 1.1428 mL | 2.2855 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
