Acalisib

SKU: orb1223796

Description

Acalisib (GS-9820, CAL-120) is a potent, isoform-selective PI3K p110δ with IC50 of 12.7 nM, displays >100-fold selectivity over P110α/β/γ, and other class II/III PI3Ks, DNA-PK, mTOR; inhibits anti-FC RI PI3Kδ induced CD63 expression with IC50 of 14 nM in human whole blood with IC50 of 14 nM; induces osteoclast retraction in rat osteoclasts, disrupts actin belts and blocks RANKL-stimulated osteoclast survival.Blood Cancer Phase 2 Clinical(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.\n(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.

Key Properties

• CAS Number: 870281-34-8
• MW: 401.3965
• Purity: >98% (HPLC)
• Formula: C₂₁H₁₆FN₇O
• SMILES: O=C1N(C2=CC=CC=C2)C([C@@H](NC3=C4NC=NC4=NC=N3)C)=NC5=C1C=C(F)C=C5
• Target: PI3K
• Solubility: DMSO: ≥ 29 mg/mL

Bioactivity

• 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.
• 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.

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

GS-9820 | GS9820 | GS 9820 | CAL-120 | CAL120 | CAL 120

Quick Database Links

Gene Symbol

PI3K