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Technical Data
| Formula | C17H23N5O2S2 |
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| Molecular Weight | 393.53 | CAS No. | 1166227-08-2 | |
| Solubility (25°C)* | In vitro | DMSO | 79 mg/mL (200.74 mM) | |
| Ethanol | 2 mg/mL (5.08 mM) | |||
| Water | Insoluble | |||
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* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. * Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.) |
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Biological Activity
| Description | A66 is a potent and specific p110α inhibitor with IC50 of 32 nM in a cell-free assay, >100 fold selectivity for p110α over other class-I PI3K isoforms. | ||||||||
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| Targets |
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| In vitro | In addition to the wild-type p110α, A66 also potently inhibits the oncogenic forms of p110α such as p110α E545K and p110α H1047R with IC50 of 30 nM and 43 nM, respectively. Unlike PIK-75, A66 displays >100 fold selectivity for p110α over other class-I PI3K isoforms. Among the class-II PI3Ks, class-III PI3K and PI4Ks, A66 only exhibits limited cross-reactivity with the class-II PI3K PI3KC2β and the PI4Kβ isoform of PI4K with IC50 of 462 nM and 236 nM, respectively. A66 exhibits no inhibitory activity against other lipid kinases or the related kinases DNA-PK and mTOR. A66 has a higher degree of specificity compared with PIK-75 when tested at 10 μM against two large panels of 110 protein kinases and 318 kinases. Inhibition of p110α alone by A66 treatment is sufficient to block insulin signalling to Akt/PKB in certain cell lines that harbor H1047R mutations in PIK3CA and have high levels of p110α and class-Ia PI3K activity. [1] A66 treatment at 0.7 μM induces a 75-80% reduction in focus formation by the highly transforming p85α iSH2 mutants KS459delN, DKRMN-S560del, and K379E, and reduces the phosphorylation of Akt on T308 by all p85 mutants. [2] | ||||||||
| In vivo | A single dose of A66 at 100 mg/kg induces a profound reduction in the phosphorylation of Akt/PKB and p70 S6 kinase, but not of ERK, in SK-OV-3 tumour tissue in vivo at both 1 hour and 6 hours after dosing. A66 dosed at 100 mg/kg once daily (QD) for 21 days or 75 mg/kg twice daily (BID) for 16 days induces a significant delay in growth of SK-OV-3 xenografted tumors with average TGI of 45.9% and 29.9%, respectively, which is even greater than that induced by the well-established pan-PI3K inhibitor BEZ-235. QD dosing of A66 in the HCT-116 xenograft model also induces a significant reduction in tumour volume with TGI of 77.2%, but causes a non-significant reduction in tumor volume in the U87MG xenograft model. [1] Administration of A66 at 10 mg/kg in male CD1 mice induces significant impairments in the ITT (insulin tolerance test) and GTT (glucose tolerance test), and an increase in glucose production during a PTT (pyruvate tolerance test), almost to the same level as the pan-PI3K inhibitors. [3] | ||||||||
| Features | Highly selective for the p110α isoform. |
Protocol (from reference)
| Animal Study:[1] |
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References
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Customer Product Validation
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, , Dr. Zhang of Tianjin Medical University
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Data from [Data independently produced by , , Genes Dev, 2012, 26: 1573–1586]
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Data from [Data independently produced by , , Genes Dev, 2012, 26: 1573–1586]
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Data from [Data independently produced by , , Biochem Pharmacol, 2016, 106:56-69]
Selleck's A66 has been cited by 56 publications
| PTEN deficiency exposes a requirement for an ARF GTPase module for integrin-dependent invasion in ovarian cancer [ EMBO J, 2023, 42(18):e113987] | PubMed: 37577760 |
| PTEN deficiency exposes a requirement for an ARF GTPase module for integrin-dependent invasion in ovarian cancer [ EMBO J, 2023, 42(18):e113987] | PubMed: 37577760 |
| Platelet p110β mediates platelet-leukocyte interaction and curtails bacterial dissemination in pneumococcal pneumonia [ Cell Rep, 2022, 41(6):111614] | PubMed: 36351402 |
| (+)-Cyanidan-3-ol inhibits epidermoid squamous cell carcinoma growth via inhibiting AKT/mTOR signaling through modulating CIP2A-PP2A axis [ Phytomedicine, 2022, 101:154116] | PubMed: 35525235 |
| Upregulated Apelin Signaling in Pancreatic Cancer Activates Oncogenic Signaling Pathways to Promote Tumor Development [ Int J Mol Sci, 2022, 23-1810600] | PubMed: 36142542 |
| Enhanced Vulnerability of LKB1-Deficient NSCLC to Disruption of ATP Pools and Redox Homeostasis by 8-Cl-Ado [ Mol Cancer Res, 2022, 20(2):280-292] | PubMed: 34654720 |
| G-protein coupled receptor 34 regulates the proliferation and growth of LS174T cells through differential expression of PI3K subunits and PTEN [ Mol Biol Rep, 2022, 10.1007/s11033-021-07068-4] | PubMed: 34997428 |
| PI(3,4)P2-mediated membrane tubulation promotes integrin trafficking and invasive cell migration [ Proc Natl Acad Sci U S A, 2021, 118(19)e2017645118] | PubMed: 33947811 |
| Role of endocytosis and trans-endocytosis in ICOS costimulator-induced downmodulation of the ICOS Ligand [ J Leukoc Biol, 2021, 10.1002/JLB.2A0220-127R] | PubMed: 33527556 |
| p85β regulates autophagic degradation of AXL to activate oncogenic signaling. [ Nat Commun, 2020, 8;11(1):2291] | PubMed: 32385243 |
RETURN POLICY
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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.
NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.