SAR-260301

SKU: orb1307758

Description

SAR-260301 is a potent and selective small molecule inhibitor of PI3Kβ, exhibiting an IC50 of 23 nM and oral bioavailability. It is a valuable research tool for studying PI3Kβ signaling in oncology and thrombosis, applicable in both cellular assays and in vivo models.

Research Area

Signal Transduction

Key Properties

• CAS Number: 1260612-13-2
• MW: 354.4
• Purity: 99.74% (May vary between batches)
• Formula: C₁₉H₂₂N₄O₃
• SMILES: C[C@H]1Cc2ccccc2N1C(=O)Cc1nc(cc(=O)[nH]1)N1CCOCC1
• Target: PI3K
• Solubility: 10% DMSO+40% PEG300+5% Tween 80+45% Saline:4 mg/mL (11.29 mM);DMSO:125 mg/mL (352.71 mM)

Bioactivity

• Target IC50:
  PI3Kγ:10000 nM|PI3Kβ:23 nM|DNA-PK:2000 nM|pAkt:49 nM|PI3Kα:1539 nM|PI3KC2γ:3812 nM|VPS34:183 nM|PI3Kδ:468 nM
• In Vivo:
  SAR-260301 is well tolerated at the active dose, with no sign of toxicity and no bodyweight loss. SAR-260301 displays antitumor efficacy in human PTEN-deficient melanoma models in mice as a single agent. SAR-260301 treatment leads to a statistically significant tumor growth inhibition as measured by a ΔT/ΔC of 39% (p = 0.054 versus control mice) on day 15 post-tumor implantation. SAR-260301(p.o.) reveals sustained target inhibition (≥50%) of pAkt-S473 for at least 7 h. SAR-260301 has moderate terminal elimination half-life (t1/2=0.87 h, 1.4 h, 2.5 h, 0.87h, 6.9 h and 4.5 h for female SCID mice (3 mg/kg, iv), mice (10 mg/kg, p.o.), mice (100 mg/kg, p.o.), female nude rats (3 mg/kg, iv), rat (10 mg/kg, p.o.), male beagle dogs (10 mg/kg, p.o.)) .
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• In Vitro:
  SAR-260301 inhibits pAktS473 (a measured IC50: 0.06 μM and an estimated IC90: 2 μM), in the UACC-62 tumor cell line assay. SAR260301 inhibits PI3Kβ-dependent proliferation/viability in low serum conditions (IC50: 196 nM), in the MEF-3T3-myr-p110β mechanistic model. SAR260301 inhibits LNCaP cell proliferation in low and high serum conditions (IC50: 2.9 and 5.0 μM, respectively), after 4-day treatment, whereas it is inactive in these conditions in PC3 cells at concentrations up to 10 μM, despite target engagement). SAR260301 also leads to antitumor activities in PTEN-deficient/BRAF-mutant human melanoma cells, inhibiting cell proliferation (IC40: 6.5 and 3.3 μM for UACC-62 and WM-266.4, respectively, after 4-day treatment). After prolonged treatment, SAR260301 at 3 or 10 μM inhibits PC3 cell proliferation in low serum conditions, with a cytostatic effect achieved for 14 days, despite some cell death induction observed at 10 μM .
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Storage & Handling

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

Alternative Names

DNA-PK, pAkt, PI3Kδ, PI3Kβ, PI3Kγ, PI3Kα, PI3KC2γ, SAR260301, SAR-260301, SAR 260301, Vps34

Compound Identifiers

PubChem CID

135565159