A66 (Synonyms: A 66; A-66) |
| Catalog No.GC17550 |
A66 is a highly specific and selective p110α inhibitor with an IC50 value of 32nM.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1166227-08-2
Sample solution is provided at 25 µL, 10mM.
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A66 is a highly specific and selective p110α inhibitor with an IC50 value of 32nM[1, 2]. A66 can also inhibit p110α mutation such as p110α E545K and p110α H1047R, which have the IC50 values of 30nM and 43nM[1]. A66 can inhibit tumor necrosis factor induced necroptosis[3].
A66 (100nM; 24h) markedly opposed the increased expression of Ido1 and Tgfb1 transcripts by TGF-β in mouse plasmacytoid dendritic cells[4]. A66 (100nM; 1h) reduced lipid kinase activity in MT (polyoma middle T antigen) tumor cells[5]. A66 (100nM; 1h) significantly inhibited the phosphorylation of Akt in human rhabdomyosarcoma Rh30 cells tranfected p110 retrovirus[6].
A66 (10mg/kg; i.p. ; 24h) induced an increase in glucose production during a pyruvate (2g/kg; i.p. ) tolerance test in mice[7]. A66 (10mg/kg; i.p. ; 21 day) significant delayed in growth of SK-OV-3 cells derived xenograft tumours in mice xenograft model (SK-OV-3 cells were subcutaneously inoculated on the right flank of the mice)[1].
References:
[1] JAMIESON S, FLANAGAN J U, KOLEKAR S, et al. A drug targeting only p110alpha can block phosphoinositide 3-kinase signalling and tumour growth in certain cell types [J]. Biochem J, 2011, 438(1): 53-62.
[2] SUN M, HILLMANN P, HOFMANN B T, et al. Cancer-derived mutations in the regulatory subunit p85alpha of phosphoinositide 3-kinase function through the catalytic subunit p110alpha [J]. Proc Natl Acad Sci U S A, 2010, 107(35): 15547-52.
[3] HU S, CHANG X, ZHU H, et al. PI3K mediates tumor necrosis factor induced-necroptosis through initiating RIP1-RIP3-MLKL signaling pathway activation [J]. Cytokine, 2020, 129(155046.
[4] IACONO A, POMPA A, DE MARCHIS F, et al. Class IA PI3Ks regulate subcellular and functional dynamics of IDO1 [J]. EMBO Rep, 2020, 21(12): e49756.
[5] UTERMARK T, RAO T, CHENG H, et al. The p110alpha and p110beta isoforms of PI3K play divergent roles in mammary gland development and tumorigenesis [J]. Genes Dev, 2012, 26(14): 1573-86.
[6] WANG X, LI J P, YANG Y, et al. A pharmacological model reveals biased dependency on PI3K isoforms for tumor cell growth [J]. Acta Pharmacol Sin, 2013, 34(9): 1201-7.
[7] SMITH G C, ONG W K, REWCASTLE G W, et al. Effects of acutely inhibiting PI3K isoforms and mTOR on regulation of glucose metabolism in vivo [J]. Biochem J, 2012, 442(1): 161-9.
| Cell experiment [1]: | |
Cell lines | Human rhabdomyosarcoma Rh30 cell line |
Preparation Method | Human rhabdomyosarcoma Rh30 cells were maintained in RPMI-1640 medium supplemented with 10% fetal bovine serum. Myristoylated tag was ligated in tandem with each p110 gene sequences and then inserted into pBabe-Puro plasmid. The resulting constructs were co-transfected with pGP and pE-Ampho plasmids into 293FT cells to obtain retrovirus, which were then used to infect Rh30 cells. After selection with 1μg/mL puromycin for 1 week, cells stably expressing myristoylated PI3K isoforms were pooled for validation and named as Rh30-Myr-p110. Rh30-Myr-p110 cells grown to 50% confluence in 12-well plates continued to be incubated in serum-free medium for 12h and were then exposed to A66 at 100nM for 1h. |
Reaction Conditions | 100nM; 1h |
Applications | A66 significantly inhibited the phosphorylation of Akt in human rhabdomyosarcoma Rh30-Myr-p110 cells. |
| Animal experiment [2]: | |
Animal models | Male CD1 mice |
Preparation Method | For glucose tolerance tests and pyruvate tolerance tests the mice were starved overnight and for the insulin tolerance test food was withdrawn 2h prior to the start of the experiments. A66 was dosed intraperitoneally 1h after the end of the dark cycle and 1h prior to the intraperitoneal dosing with glucose or pyruvate (2g/kg) or insulin (0.75unit/kg). |
Dosage form | 10mg/kg; 24h; i.p. |
Applications | A66 induced significant impairments in the insulin tolerance test and glucose tolerance test, and an increase in glucose production during a pyruvate tolerance test in mice. |
References: | |
| Cas No. | 1166227-08-2 | SDF | |
| Synonyms | A 66; A-66 | ||
| Chemical Name | (2S)-1-N-[5-(2-tert-butyl-1,3-thiazol-4-yl)-4-methyl-1,3-thiazol-2-yl]pyrrolidine-1,2-dicarboxamide | ||
| Canonical SMILES | CC1=C(SC(=N1)NC(=O)N2CCCC2C(=O)N)C3=CSC(=N3)C(C)(C)C | ||
| Formula | C17H23N5O2S2 | M.Wt | 393.53 |
| Solubility | ≥ 19.7mg/mL in DMSO | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 2.5411 mL | 12.7055 mL | 25.411 mL |
| 5 mM | 0.5082 mL | 2.5411 mL | 5.0822 mL |
| 10 mM | 0.2541 mL | 1.2706 mL | 2.5411 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
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μL
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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 20 reference(s) in Google Scholar.)
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