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My Cart> Small Molecule Compounds > Inhibitors & Antagonists & Agonists > PI3K/Akt/mTOR > CH-5132799CAS：1007207-67-1
Molecular Formula：C15H19N7O3S
Molecular Weight：377.42
Storage：Powder:2-8℃，2 years
Purity：≥98%
Appearance：White to off-white Solid
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| CAS | 1007207-67-1 |
| Name | CH-5132799 |
| Molecular Formula | C15H19N7O3S |
| Molecular Weight | 377.42 |
| Solubility | Soluble in DMSO ≥0.5mg/mL;Soluble in Water ＜ 1mg/mL |
| Purity | ≥98% |
| Appearance | White to off-white Solid |
| Storage | Powder:2-8℃，2 years |
| MDL | MFCD22419020 |
| SMILES | NC1=NC=C(C2=C3C(N(S(=O)(C)=O)CC3)=NC(N4CCOCC4)=N2)C=N1 |
| Target Point | PI3K |
| Passage | PI3K/Akt/mTOR |
| Background | CH5132799 is a selective class I PI3K inhibitor. . |
| Biological Activity | Izorlisib (CH5132799) is a selective class I PI3K inhibitor. Izorlisib inhibits class I PI3Ks， particularly PI3Kα， with an IC50 of 14 nM.[1-2] |
| In Vitro | Izorlisib(CH5132799)is a selective class I PI3K inhibitor with potent antitumor activity against tumors harboring the PIK3CA mutations. Izorlisib selectively inhibits class I PI3Ks and PI3Kα mutants in in vitro kinase assays. Izorlisib inhibits class I PI3Ks，particularly PI3Kα，with an IC50 of 14 nM. IC50 values against class II PI3Ks(C2α and C2β)，a class III PI3K(Vps34)，and a class IV PI3K(mTOR)are more than 100-fold higher than that against PI3Kα. Interestingly，slightly lower IC50 values are observed against PI3Kα with oncogenic mutations E542K，E545K，and H1047R than against wild-type(WT)PI3Kα. In an analysis of cocrystal structure with PI3Kγ(PBD ID: 3APC)，Izorlisib is shown to interact with ATP-binding sites of the enzyme，suggesting an ATP competitive mode of inhibition. No significant inhibitory activities of Izorlisib are observed against a representative panel of 26 protein kinases，including RTKs，nonreceptor tyrosine kinases，and serine/threonine kinases. These data indicate that Izorlisib is a selective class I PI3K inhibitor，especially against PI3Kα and its mutants. Izorlisib shows superior antiproliferative activity across the 4 tumor types，with 75%(45/60)of lines having an IC50 below 1 μM and 38%(23/60)of lines having an IC50 below 0.3 μM[1]. |
| In Vivo | Mice bearing BT-474 tumors(n=14)are orally administered 50 mg/kg of Everolimus on a daily basis for 31 days and then randomized. After randomization，the mice are orally administered 50 mg/kg of Everolimus(n=4)and 12.5 mg/kg(n=5)，and 25 mg/kg(n=5)of Izorlisib on a daily basis for 7 days. C，the vehicle-，Everolimus，and CH5132799-treated(25 mg/kg)tumors are resected at 4 hours after terminal administration in B，lysed，and analyzed by Western blotting. Izorlisib administration leads to a remarkable regression in a dose-dependent manner of the tumors regrown after the long-term Everolimus treatment. The tumors are resected at the end of treatment and analyzed by Western blotting with respect to PI3K pathway inhibition. Izorlisib suppresses various effectors in the PI3K pathway，including Akt，FoxO1，S6K，S6，and 4E-BP1，whereas Everolimus inhibits only phosphorylation of S6K and S6，both downstream effectors of mTORC1[1]. |
| Cell Experiment | The cell lines are added to the wells of 96-well plates containing 0.076 to 10，000 nM CH5132799 and incubated at 37°C. After 4 days of incubation，Cell Counting Kit-8 solution is added and，after incubation for several more hours，absorbance at 450 nm is measured with Microplate-Reader iMark. The antiproliferative activity is calculated. The IC50 values are calculated[1]. |
| Animal Experiment | Female BALB-nu/nu mice(CAnN.Cg-Foxn1/CrlCrlj nu/nu)are used. A total of 4×106 to 1.2×107 cells are suspended in 100 to 200 μL serum-free culture medium and injected subcutaneously into the right flank of the mice. Tumor size is measured by using a gauge twice per week，and tumor volume(TV)is calculated. Once the tumors reach a volume of approximately 200 to 300 mm3，animals are randomized into groups(n=4 or 5 in each group)and treatment is initiated. CH5132799 and Everolimus are orally administered once a day and Trastuzumab is intravenously injected once a week. |
| Data Literature Source | [1]. Tanaka H，et al. The selective class I PI3K inhibitor CH5132799 targets human cancers harboring oncogenic PIK3CA mutations. Clin Cancer Res，2011，17(10)，3272-3281. [2]. Ohwada J，et al. Discovery and biological activity of a novel class I PI3K inhibitor，CH5132799. Bioorg Med Chem Leff，2011，21(6)，1767-1772. |
| Unit | Bottle |
| Specification | 5mg |
是一种选择性的 I 类 PI3K 抑制剂，抑制 PI3Kα。
Remark：These protocols are for reference only. Solarbio does not independently validate these methods.
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