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Purity: ≥98%
Acalisib (formerly known as CAL-120; GS-9820) is a brand-new, potent, and highly selective inhibitor of p110, which has anticancer properties. P110 refers to the beta and delta isoforms of the 110 kDa catalytic subunit of class IA phosphoinositide-3 kinases (PI3K). It exhibits 114- to 400-fold selectivity over the other class I PI3K enzymes, inhibits PI3K p110 with an IC50 of 14 nM, and has no effect on Class II or III PI3K family members or other PI3K-related proteins like mTOR and DNA-PK. Acalisib may have anticancer and immunomodulating effects. In cancer cells, PI3K-mediated signaling is frequently dysregulated. By preventing the synthesis of the second messenger phosphatidylinositol-3,4,5-trisphosphate (PIP3), which reduces tumor cell proliferation and triggers cell death, acalisib inhibits the activity of PI3K.
| Targets |
p110α (IC50 = 5441 nM); p110β (IC50 = 3377 nM); p110δ (IC50 = 12.7 nM); p110γ (IC50 = 1389 nM); hVps34 (IC50 = 12682 nM); DNA-PK (IC50 = 18749 nM)
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| ln Vitro |
Acalisib (GS-9820) to other PI3K class I enzymes (IC50: PI3K, 5,441 nM; PI3K, 3,377 nM; PI3K, 1,389 nM), PI3K is more selective for Acalisib (IC50=12.7 nM). Additionally, compared to related kinases like PI3KCII (IC50>10 nM), hVPS34 (IC50=12.7 M), DNA-PK (IC50=18.7 M), and mTOR (IC50>10 nM), acalisib is 103-fold more selective against PI3K. Both the GPCR for lysophosphatidic acid (LPA) and the PDGF receptor signal through PI3K in fibroblasts. At 11,585 nM, acalisib reduces PDGF-induced pAkt by 50%, and at 2,069 nM, it reduces LPA-induced pAkt by 50%.
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| ln Vivo |
Obese hyperphagic ob/ob mice are treated with either BYL-719, a selective PI3K inhibitor, or Acalisib (GS-9820), a selective PI3K inhibitor, to examine the relative roles of PI3K and PI3K inhibition in the prevention of obesity. Surprisingly, after 15 days of treatment, BYL-719 reduces body weight to a degree comparable to CNIO-PI3Ki, whereas Acalisib has no noticeable effect at the same doses as BYL-719. It should be noted that mice with multiple myeloma xenografts can grow less rapidly when given 10 mg/kg of acalisib[2].
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| Enzyme 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].
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| Cell Assay |
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| Animal Protocol |
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. |
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| References |
| Molecular Formula |
C21H16FN7O
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| Molecular Weight |
401.4
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| Exact Mass |
401.14
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| Elemental Analysis |
C, 62.84; H, 4.02; F, 4.73; N, 24.43; O, 3.99
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| CAS # |
870281-34-8
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| Related CAS # |
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| Appearance |
Solid powder
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| SMILES |
O=C1N(C2=CC=CC=C2)C([C@@H](NC3=C4NC=NC4=NC=N3)C)=NC5=C1C=C(F)C=C5
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| InChi Key |
DOCINCLJNAXZQF-LBPRGKRZSA-N
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| InChi Code |
InChI=1S/C21H16FN7O/c1-12(27-19-17-18(24-10-23-17)25-11-26-19)20-28-16-8-7-13(22)9-15(16)21(30)29(20)14-5-3-2-4-6-14/h2-12H,1H3,(H2,23,24,25,26,27)/t12-/m0/s1
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| Chemical Name |
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| Synonyms |
Acalisib; CAL120; CAL 120; CAL-120; GS-9820; GS9820; GS 9820
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.23 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (6.23 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (6.23 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4913 mL | 12.4564 mL | 24.9128 mL | |
| 5 mM | 0.4983 mL | 2.4913 mL | 4.9826 mL | |
| 10 mM | 0.2491 mL | 1.2456 mL | 2.4913 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Status | Interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT01705847 | Completed | Drug: GS-9820 | Lymphoid Malignancies | Gilead Sciences | November 2012 | Phase 1 |
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