870281-34-8
870281-34-8 structure
- Name: Acalisib
- Chemical Name: 6-fluoro-3-phenyl-2-[(1S)-1-(7H-purin-6-ylamino)ethyl]quinazolin-4-one
- CAS Number: 870281-34-8
- Molecular Formula: C21H16FN7O
- Molecular Weight: 401.396
- Catalog: Research Areas Cancer
- Create Date: 2017-05-24 09:37:57
- Modify Date: 2024-01-02 22:16:56
-
Acalisib is a potent and selective PI3Kδ inhibitor with an IC50 of 12.7 nM.
| Name | 6-fluoro-3-phenyl-2-[(1S)-1-(7H-purin-6-ylamino)ethyl]quinazolin-4-one |
|---|---|
| Synonyms |
4(3H)-Quinazolinone, 6-fluoro-3-phenyl-2-[(1S)-1-(7H-purin-6-ylamino)ethyl]-
6-Fluoro-3-phenyl-2-[(1S)-1-(7H-purin-6-ylamino)ethyl]-4(3H)-quinazolinone UNII-OVW60IDW1D Acalisib |
| Description | Acalisib is a potent and selective PI3Kδ inhibitor with an IC50 of 12.7 nM. |
|---|---|
| Related Catalog | |
| Target |
p110δ:12.7 nM (IC50) p110γ:1389 nM (IC50) p110β:3377 nM (IC50) p110α:5441 nM (IC50) hVps34:12682 nM (IC50) DNA-PK:18749 nM (IC50) |
| In Vitro | Acalisib (GS-9820) is more selective for PI3Kδ (IC50=12.7 nM) relative to other PI3K class I enzymes (IC50: PI3Kα, 5,441 nM; PI3Kβ, 3,377 nM; PI3Kγ, 1,389 nM). Acalisib is also 103-fold more selective against PI3Kδ than against related kinases, such as PI3KCIIβ (IC50>10 nM), hVPS34 (IC50=12.7 μM), DNA-PK (IC50=18.7 μM), and mTOR (IC50>10 nM). In fibroblasts, the PDGF receptor signals through PI3Kα and the GPCR for lysophosphatidic acid (LPA) signals through PI3Kβ. Acalisib reduces PDGF-induced pAkt by only 50% at 11,585 nM, and LPA-induced pAkt by 50% at 2,069 nM. |
| In Vivo | To dissect the relative contribution of PI3Kα and PI3Kδ inhibition in the reduction of obesity, obese hyperphagic ob/ob mice are treated with a selective PI3Kα inhibitor, BYL-719, or with a selective PI3Kδ inhibitor, Acalisib (GS-9820). Remarkably, BYL-719 reduces body weight after 15 days of treatment to a similar extent as CNIO-PI3Ki, whereas Acalisib has no significant effect at the same doses as BYL-719. It should be noted that 10 mg/kg of Acalisib is sufficient to reduce the growth of multiple myeloma xenografts in mice[2]. |
| Kinase Assay | Biochemical in vitro lipid kinase assays are performed. A stock solution of Acalisib (GS-9820) is prepared in DMSO at a concentration of 10 mM. Ten-point kinase inhibitory activities are measured over a concentration range (5 to 104 nM) with ATP at a concentration consistent with the Km of each of the enzymes[1]. |
| Cell Assay | The effect of inhibitors on RAW264.7 cell survival is evaluated using the MTT assay. RAW264.7 cells are seeded in Falcon flat bottom 96-well plates at a density of 2.5-3×104 cells/cm2 in 100 μL of DMEM with 10% FBS and 1% antibiotic solution. After seeding, the cells are allowed to attach for 24 h then exposed to control or Acalisib (GS-9820) (100 pM to 10 μM) for 24 h. After incubation at 37°C in 5% CO2, MTT substrate is added at a final concentration of 0.5 mg/mL for 4 h. Following a 4-h incubation, 100 μL of solubilization solution is added to each well to dissolve the formazan crystals and samples are analyzed after 24 h. Absorbance of the samples is assessed using a plate reader using a wavelength of 550 nm and a reference wavelength of 700 nm[1]. |
| Animal Admin | Mice[2] Ob/ob C57BL6J mice and Wild-type C57BL6J/Ola.Hsd mice are housed under specific pathogen free (SPF) conditions, at 22°C, and with 12 hours dark/light cycles (light cycle from 8 am to 8 pm). All mice used are males of 20 weeks of age. Mice are fed with standard chow diet (18% of fat-based caloric content). PI3K inhibitors are administered daily by oral gavage during 15 or 16 days as follows, BYL-719 (5 and 10 mg/kg) and Acalisib (5 and 10 mg/kg), CNIO-PI3Ki (1 and 5 mg/kg), dissolved in PEG-300 and 10% N-methyl-2-pyrrolidone. |
| References |
| Density | 1.5±0.1 g/cm3 |
|---|---|
| Boiling Point | 733.7±70.0 °C at 760 mmHg |
| Molecular Formula | C21H16FN7O |
| Molecular Weight | 401.396 |
| Flash Point | 397.5±35.7 °C |
| Exact Mass | 401.140045 |
| PSA | 101.38000 |
| LogP | 2.43 |
| Vapour Pressure | 0.0±2.4 mmHg at 25°C |
| Index of Refraction | 1.759 |