A66

製品コードS2636 バッチS263601

化学情報

	Synonyms	N/A	Storage (From the date of receipt)	3 years -20°C powder 1 years -80°C in solvent
	化学式	C₁₇H₂₃N₅O₂S₂
	分子量	393.53	CAS No.	1166227-08-2
Solubility (25°C)*	体外	DMSO	79 mg/mL (200.74 mM)
		Ethanol	2 mg/mL (5.08 mM)
		Water	Insoluble
* <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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明	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.
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]
特徴	Highly selective for the p110α isoform.

プロトコル(参考用のみ)

キナーゼアッセイ	PI3K (human) HTRF Assay
キナーゼアッセイ	The p110α isoform is produced in-house by co-expressing full-length human p85α with the indicated human full-length catalytic subunit containing a histidine tag at the N-terminus to allow purification. The p110α is titrated and used at a concentration between EC65-EC80 values. IC50 value is evaluated using the PI3K (human) HTRF Assay.
動物実験	動物モデル	Age-matched specific pathogen-free Rag1^-/- or NIH-III mice inoculated subcutaneously with U87MG, SK-OV-3 or HCT-116 cells
	投薬量	100 mg/kg once daily (QD) or 75 mg/kg twice daily (BID)
	投与方法	Intraperitoneal injection

参考

カスタマーフィードバック

: , , Dr. Zhang of Tianjin Medical University

: Data from [Data independently produced by , , Genes Dev, 2012, 26: 1573–1586]

: Data from [Data independently produced by , , Genes Dev, 2012, 26: 1573–1586]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

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

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人間や獣医の診断であるか治療的な使用のためにでない。

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