SAR-260301

Additional information:
SAR-260301 is an orally available and selective PI3Kβ inhibitor with an IC50 of 23 nM.|Product information|CAS Number: 1260612-13-2|Molecular Weight: 354.40|Formula: C19H22N4O3|Chemical Name: 2-2-[(2S)-2-methyl-2,3-dihydro-1H-indol-1-yl]-2-oxoethyl-6-(morpholin-4-yl)-1,4-dihydropyrimidin-4-one|Smiles: C[C@H]1CC2C=CC=CC=2N1C(=O)CC1NC(=CC(=O)N=1)N1CCOCC1|InChiKey: UAXHPOBBKRWJGA-ZDUSSCGKSA-N|InChi: InChI=1S/C19H22N4O3/c1-13-10-14-4-2-3-5-15(14)23(13)19(25)11-16-20-17(12-18(24)21-16)22-6-8-26-9-7-22/h2-5,12-13H,6-11H2,1H3,(H,20,21,24)/t13-/m0/s1|Technical Data|Appearance: Solid Power|Purity: ≥98% (or refer to the Certificate of Analysis)|Solubility: DMSO : 125 mg/mL (352.71 mM; Need ultrasonic).|Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis|Storage Condition: Dry, dark and -20 oC for 1 year or refer to the Certificate of Analysis.|Shelf Life: ≥12 months if stored properly.|Stock Solution Storage: 0 – 4 oC for 1 month or refer to the Certificate of Analysis.|Drug Formulation: To be determined|HS Tariff Code: 382200|How to use|In Vitro:|In the UACC-62 tumor cell line assay, SAR-260301 inhibits pAktS473 with a measured IC50 at 0.06 μM and an estimated IC90 at 2 μM. In MEF-3T3-myr-p110β mechanistic model, SAR260301 inhibits PI3Kβ-dependent proliferation/viability in low serum conditions with an IC50 of 196 nM. In PTEN-deficient human prostate tumor cells, SAR260301 inhibits LNCaP cell proliferation in low and high serum conditions with IC50 values of 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. 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. SAR260301 also leads to antitumor activities in PTEN-deficient/BRAF-mutant human melanoma cells, inhibiting cell proliferation with IC40 values of 6.Garadacimab Factor Xa 5 and 3.Sonidegib site 3 μM for UACC-62 and WM-266.PMID:35123874 4, respectively, after 4-day treatment.|In Vivo:|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 is well tolerated at the active dose, with no sign of toxicity and no body weight loss. Oral administration of SAR-260301 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, po), mice (100 mg/kg, po), female nude rats (3 mg/kg, iv), rat (10 mg/kg, po), male beagle dogs (10 mg/kg, po)).|Products are for research use only. Not for human use.|