Uses
SRX3207 is an orally active and first-in-class dual Syk/PI3K inhibitor, with IC50 values of 10.7 nM and 861 nM for Syk and PI3Kα, respectively. SRX3207 relieves tumor immunosuppression[1][2].
Biological Activity
SRX3207 is an orally active and first-in-class dual Syk/PI3K inhibitor, with IC50 values of 10.7 nM and 861 nM for Syk and PI3Kα, respectively. SRX3207 relieves tumor immunosuppression[1][2].
SRX3207 (10 μmol/L) is able to block p-AKT at concentration[1].SRX3207 has sufficient solubility in water (43 μmol/L)[1].
SRX3207 (10 mg/kg, orally) increases antitumor immune response[1].
in vivo
SRX3207 (10 mg/kg, orally) increases antitumor immune response[1].
| Animal Model: | LLC or B16 or B16-OVA or CT26 (1 × 105) cells were injected subcutaneously into syngeneic mice[1]. |
| Dosage: | 10 mg/kg. |
| Administration: | Orally, starting from day 10 when tumors reached 100 mm3 until tumors were harvested on day 21. |
| Result: | Blocked phosphorylation of Syk at 348 site and Y525/526 site.
Blocked immunosuppressive MΦ polarization.
Blocked tumor growth and increased survival effectively.
|
IC 50
Syk: 10.7 nM (IC
50); PI3Kα: 861 nM (IC
50); PI3Kδ: 1280 nM (IC
50); PI3Kγ: 11100 nM (IC
50); Zap70: 1300 nM (IC
50)
References
[1]. Shweta Joshi, et al. Macrophage Syk-PI3Kγ Inhibits Antitumor Immunity: SRX3207, a Novel Dual Syk-PI3K Inhibitory Chemotype Relieves Tumor Immunosuppression. Molecular Cancer Therapeutics. 2020. [2]. Shweta Joshi, et al. Macrophage Syk-PI3Kγ Inhibits Antitumor Immunity: SRX3207, a Novel Dual Syk-PI3K Inhibitory Chemotype Relieves Tumor Immunosuppression. Mol Cancer Ther. 2020 Mar;19(3):755-764.
![7H-Thieno[3,2-b]pyran-7-one, 3-[4-[[4-[4-(1-azetidinylmethyl)-3-methyl-1H-pyrazol-1-yl]-2-pyrimidinyl]amino]phenyl]-5-(4-morpholinyl)- Structure](https://www.chemicalbook.com/CAS/20200611/GIF/2254693-15-5.gif)
