XL147 is an orally-available, reversible and competitive ATP inhibitor of the PI3K class of kinases with potencies of 39 nM, 36 nM, and 23 nM, for isoforms PI3Ka, PI3Kd, PI3Kg, respectively. [1] It is highly selective versus mTOR (>15000 nM) and DNA-PK (4750 nM). and a broad panel of >130 human protein kinases. In cellular assays, XL147 acts as an antagonist on the production of the second messenger phosphatidylinositol-3,4,5-triphosphate (PIP3), resulting in dose-dependent downstream inhibition of phosphorylation of Akt, ribosomal S6K, and ribosomal S6 protein. [1] In MCF7 and PC-3 cell lines, XL147 inhibits pAkt (T308) at 942 and 400 nM, respectively, and inhibits pAkt (S473) at 596 and 310 nM, respectively.
XL147 has been studied as a potentiator of antitumor efficacy of paclitaxel and carboplatin without increased toxicity. [2] XL147 also works synergistically with EGFR inhibitors such as erlotinib. [3]
Technical information:
| Chemical Formula: | C21H16N6O2S2 | |
| CAS #: | 956958-53-5 | |
| Molecular Weight: | 448.52 | |
| Purity: | >98% | |
| Appearance: | Green | |
| Chemical Name: | N-(3-(benzo[c][1,2,5]thiadiazol-5-ylamino)quinoxalin-2-yl)-4-methylbenzenesulfonamide | |
| Solubility: | Up to 100 mM in DMSO | |
| Synonyms: | XL-147, XL147 |
Shipping Condition: The product is shipped in a glass vial at ambient temperature.
Storage condition: For longer shelf life, store solid powder at 4oC desiccated, or store DMSO solution at -20oC.
Reference:
| 1. | Shapiro et al., Targeting Aberrant PI3K Pathway Signaling With XL147, a Potent, Selective, and Orally Bioavailable PI3K Inhibitor. AACR-NCI-EORTC poster, Oct. 2007. |
| 2. | Traynor et al., A Phase 1 safety and pharmacokinetic (PK) study of the PI3K inhibitor XL147 (SAR245408) in combination with paclitaxel and carboplatin in patients with advanced solid tumors. ASCO poster, 2010. |
| 3. | Moldovan et al., A Phase 1 Safety and Pharmacokinetic (PK) Study of the PI3K Inhibitor XL147 (SAR245408) in Combination with Erlotinib in Patients with Advanced Solid Tumors. ASCO poster, 2010. |
Other Information:
Product Specification (pdf)
MSDS (pdf)
Certificate of Analysis is available upon request.
