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XL-147 SAR245408 Pilaralisib 956958-53-5
XL147 is a potent and orally active inhibitor that targets Class I PI3Ks with IC50 values in the nanomolar level. It has PI3K inhibition activities with IC50 of 39,383,36, and 23nM for PI3Kα, PI3Kβ, PI3Kδ,PI3Kγ, respectively.[1]
| Cas No. | 956958-53-5 |
| Synonyms | Pilaralisib, SAR245408 |
| Chemical Name | N-[3-(2,1,3-benzothiadiazol-5-ylamino)quinoxalin-2-yl]-4-methylbenzenesulfonamide |
| Canonical SMILES | CC1=CC=C(C=C1)S(=O)(=O)NC2=NC3=CC=CC=C3N=C2NC4=CC5=NSN=C5C=C4 |
| Formula | C21H16N6O2S2 |
| M.Wt | 448.52 |
| Storage | Store at -20°C |
| Solubility | ≥ 22.45mg/mL in DMSO with gentle warming |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the solubility of the product in different solvents; once the solution is prepared, please store it in separate packages to avoid product failure caused by repeated freezing and thawing.Storage method and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored at -20°C, please use it within 1 month. |
To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. | |
| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. |
PI3Ks are a family of enzymes, which phosphorylate the 3'- OH position of the inositol ring of phosphoinositides.PI3Ks are divided into three classes based on structural features and in vitro lipid substrate specificity. The three class-Ia PI3K (p110 α / β / δ ) and the sole class-Ib PI3K (p110 γ ) couple growth factor receptors and G-protein-coupled receptors, respectively, to a wide range of downstream pathways. Signal transduction via the PI3K/Akt pathway is essential for regulating cellular functions, including proliferation, survival, migration, motility and tumorigenesis, in a variety of cell types. XL147 is a reversible ATP-competitive inhibitor, yet is highly selective against over 130 human protein kinases.[1]
MCF7 and PC-3 cell lines were treated with XL147 led to a reduction in the levels of phosphatidylinositol-3,4,5-tris-phosphate (PIP3) and decline in phosphorylation of AKT and ribosomal S6 protein, which are two downstream effectors of PI3K signaling. Furthermore, XL147 demonstrates potent anti-angiogenic effects in tubule formation driven by vascular endothelial growth factor and potent inhibition of cell migration stimulated by hepatocyte growth factor . [1]
Oral administration of XL147 results in eminent inhibition of tumor growth in mice bearing xenografts in which PI3K signaling is activated, including the PTEN-deficient PC-3 prostate adenocarcinoma and MDA-MB-468 breast adenocarcinoma models, and the K-Ras activated Calu-6 non-small cell lung carcinoma model. These effects on pathway signaling correlate with inhibiting tumor cell proliferation, inhibiting tumor angiogenesis, and inducing apoptosis as determined by immunohistochemical analysis. Moreover, combining XL147 in these models with other mTOR/Raptor inhibitors, such as the chemotherapeutic agents paclitaxel and carboplatin, results in enhanced anti-tumor efficacy associated with a substantial increase in apoptosis when compared to the individual agents alone. [2]
References:
1.Shapiro G, Edelman G, Calvo E, et al. Targeting aberrant PI3K pathway signaling with XL147, a potent, selective, and orally bioavailable PI3K inhibitor[J]. Proc 97th Annu Meet AACR, 2007: 14-18.
2.Traynor A M, Kurzrock R, Bailey H H, et al. A phase I safety and pharmacokinetic (PK) study of the PI3K inhibitor XL147 (SAR245408) in combination with paclitaxel (P) and carboplatin (C) in patients (pts) with advanced solid tumors[J]. J Clin Oncol, 2010, 28(15s): 3078.
For Research Use Only. Not Intended for Diagnostic or Therapeutic Use.