Zandelisib (ME401; ME-401) is a novel, potent, orally bioavailable, and selective phosphatidylinositol 3-kinase delta (PI3Kδ) inhibitor with potential anticancer activity. It inhibits PI3Kδ with an IC50 of 3.5 nM. Zandelisib is being developed in a phase II clinical trial for the treatment of follicular lymphoma and other B-cell malignancies.
Physicochemical Properties
| Molecular Formula | C₃₁H₃₈F₂N₈O |
| Molecular Weight | 576.68 |
| Exact Mass | 576.313 |
| CAS # | 1401436-95-0 |
| PubChem CID | 66571003 |
| Appearance | White to off-white solid powder |
| Boiling Point | 729.2±70.0 °C(Predicted) |
| LogP | 5.7 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 10 |
| Rotatable Bond Count | 8 |
| Heavy Atom Count | 42 |
| Complexity | 855 |
| Defined Atom Stereocenter Count | 0 |
| InChi Key | WPFUFWIHMYZXSF-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C31H38F2N8O/c1-31(2,20-22-8-4-5-9-23(22)21-12-14-39(3)15-13-21)38-28-35-29(40-16-18-42-19-17-40)37-30(36-28)41-25-11-7-6-10-24(25)34-27(41)26(32)33/h4-11,21,26H,12-20H2,1-3H3,(H,35,36,37,38) |
| Chemical Name | 4-[2-(difluoromethyl)benzimidazol-1-yl]-N-[2-methyl-1-[2-(1-methylpiperidin-4-yl)phenyl]propan-2-yl]-6-morpholin-4-yl-1,3,5-triazin-2-amine |
| Synonyms | ZandelisibME401ME-401ME 401 |
| 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
| ln Vitro | Zandelisib inhibits PI3Ks, with IC50 values for p110α, p110β, p110γ, and p110δ of 4, 976 nM, 605 nM, 817 nM, and 3.5 nM, respectively [1]. |
| References |
[1]. Combination therapy. WO2019183226A1. [2]. (sulfinyl and sulfonyl benzimidazolyl) pyrimidines and triazines, pharmaceutical compositions thereof, and their use for treating proliferative diseases. WO2014055647A1. |
| Additional Infomation |
Zandelisib is an orally bioavailable inhibitor of the delta isoform of phosphatidylinositide 3-kinase (PI3K), with potential antineoplastic activity. Upon oral administration, zandelisib selectively inhibits the delta isoform of PI3K and prevents the activation of the PI3K/AKT signaling pathway. This both decreases proliferation and induces cell death in PI3K-delta-overexpressing tumor cells. PI3K-delta plays a key role in the proliferation and survival of hematologic cancer cells. The targeted inhibition of PI3K-delta is designed to preserve PI3K signaling in normal, non-neoplastic cells. PI3K, an enzyme often overexpressed in cancer cells, plays a crucial role in tumor cell regulation and survival. Drug Indication Treatment of mature B-cell neoplasms |
Solubility Data
| Solubility (In Vitro) | DMSO : ~33.33 mg/mL (~57.80 mM ) |
| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (4.34 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: ≥ 2.5 mg/mL (4.34 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 | 1.7341 mL | 8.6703 mL | 17.3406 mL | |
| 5 mM | 0.3468 mL | 1.7341 mL | 3.4681 mL | |
| 10 mM | 0.1734 mL | 0.8670 mL | 1.7341 mL |