A66 is a novel small molecule inhibitor of PI3K p110α with IC50 values of 32, 30 and 43 nM for p110α, p110α/E545K and p110α/H1047R. A66, showing the S-enantiomer to be a highly specific and selective p110α inhibitor. The responsive cell lines all harboured H1047R mutations in PIK3CA and have high levels of p110α and class-Ia PI3K activity. A66 is more than 100 fold less active against the other class-I PI 3-kinase isoforms and had not inhibitory activity against 200 protein kinases when tested at 10 micromolar. This makes it the most selective and specific p110α inhibitor available for research purposes.
Cell Commun Signal. 2022 Jul 7;20(1):102.
Circular dorsal ruffles disturb the growth factor-induced PI3K-AKT pathway in hepatocellular carcinoma Hep3B cells
A66 purchased from AbMole
Front Cell Dev Biol. 2021 Aug 6;9:649656.
PI3K Plays an Essential Role in Planarian Regeneration and Tissue Maintenance
A66 purchased from AbMole
OncoImmunology. 2018 Jan 1.
A PI3K p110α-selective inhibitor enhances the efficacy of anti-HER2/neu antibody therapy against breast cancer in mice
A66 purchased from AbMole
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Source | OncoImmunology (2017). Figure 4. A66 (Abmole Bioscience, Houston, TX, USA) |
| Method | oral gavage | |
| Cell Lines | BALB/C mice | |
| Concentrations | 100 mg/kg | |
| Incubation Time | 3 d | |
| Results | Under CD8+ T cell depletion, the anti-tumor efficacy of antineu antibody alone or in combination with GDC-0941 was slightly reduced, whereas that of antibody plus A66 was completely abolished |
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Source | OncoImmunology (2017). Figure 3. A66 (Abmole Bioscience, Houston, TX, USA) |
| Method | sulforhodamine B assay | |
| Cell Lines | TUBO-P2J cells | |
| Concentrations | 1 μM | |
| Incubation Time | 48 h | |
| Results | Furthermore, A66 in combination with the antibody prolonged survival |
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Source | OncoImmunology (2017). Figure 1. A66 (Abmole Bioscience, Houston, TX, USA) |
| Method | oral gavage | |
| Cell Lines | BALB/C mice | |
| Concentrations | 100 mg/kg | |
| Incubation Time | 3 d | |
| Results | In contrast to the pan-PI3K inhibitor, a PI3K p110α isoform-selective inhibitor (A66) alone had less effect on cell viability; however, anti-neu antibody combined with A66 acted synergistically to inhibit tumor cell survival |
| Cell Experiment | |
|---|---|
| Cell lines | CD4+ T lymphocytes |
| Preparation method | T lymphocyte isolation and activation To obtain naive CD4+ T lymphocytes (CD4+CD62L+ T cells), spleens were passed through a 70 lm mesh. After centrifugation, red blood cells were lysed and the cells washed in culture medium (Click’s medium supplemented with 10% heat inactivated FCS). Then, naive CD4+ T cells were isolated using Miltenyi CD4+CD62L+ T cell isolation kit II for mouse cells (Ref. 130-093-227, Miltenyi Biotec, Bergisch Gladbach, Germany) according to the manufacturers’ instructions. The isolated cells were routinely >97% CD4+, >95% CD62L+. Cells (106) were cultured in 1 ml culture medium in 24- well culture plates (Costar) pre-coated with anti-CD3 antibody (YCD3-1, 5 lg ml 1). Where indicated, anti-CD28 (H57, 2.5 lg ml 1, eBioscience, San Diego, California), DMSO or inhibitors dissolved in DMSO (1 ll per culture) were added. At 24 h, the cultures were resuspended, centrifuged and the supernatants assayed for cytokine content. |
| Concentrations | 0~10 μ M |
| Incubation time | 24 h |
| Animal Experiment | |
|---|---|
| Animal models | mice bearing SK-OV-3, HCT-116 and U87MG xenograft models |
| Formulation | 20% 2-hydroxypropyl-β-cyclodextrin (Sigma–Aldrich) in water |
| Dosages | 10 ml/kg once daily (QD) or twice daily (BID) daily for 21 days or twice daily for 16 days (SK-OV-3), daily for 14 days (U87MG) and daily for 7 days (HCT-116) |
| Administration | intraperitoneal injection |
| Molecular Weight | 393.53 |
| Formula | C17H23N5O2S2 |
| CAS Number | 1166227-08-2 |
| Solubility (25°C) | DMSO 50 mg/mL |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
| Species | Mouse | Rat | Rabbit | Guinea pig | Hamster | Dog |
| Weight (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
| Body Surface Area (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
| Km factor | 3 | 6 | 12 | 8 | 5 | 20 |
| Animal A (mg/kg) = Animal B (mg/kg) multiplied by | Animal B Km |
| Animal A Km |
For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.
| Related PI3K Products |
|---|
| SNV4818
SNV4818 is a potential best-in-class (best-in-class) mutation-selective PI3K-α inhibitor with excellent selectivity for the H1047X mutant and moderate selectivity for the related E545/542X mutant. |
| hSMG-1 inhibitor 11j
hSMG-1 inhibitor 11j, a pyrimidine derivative, is a potent and selective inhibitor of hSMG-1, with an IC50 of 0.11 nM. |
| RLY-2608
RLY-2608 is a first-in-class, orally active, selective inhibitor of PI3Ka metabolism. |
| EDI048
EDI048 is an orally active Cryptosporidium PI4K inhibitor for the research of cryptosporidiosis. |
| PI3Kδ-IN-13
PI3Kδ-IN-13 is a PI3Kδ inhibitor (IC50=2.6 nM). |
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