SAR-260301
Modify Date: 2024-01-07 06:45:34
SAR-260301 structure
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Common Name | SAR-260301 | ||
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| CAS Number | 1260612-13-2 | Molecular Weight | 354.403 | |
| Density | 1.4±0.1 g/cm3 | Boiling Point | N/A | |
| Molecular Formula | C19H22N4O3 | Melting Point | N/A | |
| MSDS | N/A | Flash Point | N/A | |
Use of SAR-260301SAR-260301 is a selective PI3Kβ inhibitor with an IC50 of 23 nM. |
| Name | sar260301 |
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| Synonym | More Synonyms |
| Description | SAR-260301 is a selective PI3Kβ inhibitor with an IC50 of 23 nM. |
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| Related Catalog | |
| Target |
PI3Kβ:23 nM (IC50) PI3Kδ:468 nM (IC50) PI3Kα:1539 nM (IC50) PI3Kγ:10000 nM (IC50) Vps34:183 nM (IC50) PI3KC2γ:3812 nM (IC50) pAkt:49 nM (IC50) DNA-PK:2000 nM (IC50) |
| 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[1]. 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 6.5 and 3.3 μM for UACC-62 and WM-266.4, respectively, after 4-day treatment[2]. |
| 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))[1]. |
| Cell Assay | Cell proliferation is measured by quantifying intracellular ATP using CellTiter-Glo kit. Cells seeded into 96-well black microplates in complete medium, are treated with single or combined agents (e.g., SAR260301) 0.3 nM-30 μM (0.1% DMSO final concentration) for 96 hours. A matrix of concentrations is prepared to allow the interaction between two compounds at different proportions/ratios, each corresponding to a “ray”. The design includes one ray for each single agent (Rays 1 and 5) and 4 for combinations. The effective fractions, corresponding to the proportional effect of each compound alone according to their IC40 value, are estimated between 0.05 and 0.95. The combination rays correspond to SAR26030:Vemurafenib or SAR260301:Selumetinib ratio of 1:3, 1:1, 3:1 and 9:1, estimated based on effective fractions. These fractions are based on IC40 calculations because SAR260301 single agent being poorly active, IC40 values are better estimated than IC50[2]. |
| Animal Admin | Mice[1] SAR-260301 is evaluated for its antitumor effects in UACC-62 melanoma subcutaneous xenografts in SCID mice. Tumors are allowed to reach at least 150 mm3 before treatment, and tumor volume is measured regularly over the treatment period. Mice are treated orally with SAR-260301 at the dose of 150 mg/kg using a bidaily (BID) schedule in order to favor sustained pathway inhibition and allow comparison with the study performed in PC3 model[1]. |
| References |
| Density | 1.4±0.1 g/cm3 |
|---|---|
| Molecular Formula | C19H22N4O3 |
| Molecular Weight | 354.403 |
| Exact Mass | 354.169189 |
| PSA | 78.53000 |
| LogP | 2.26 |
| Index of Refraction | 1.683 |
| Storage condition | 2-8℃ |
| 2-{2-[(2S)-2-methyl-2,3-dihydro-1H-indol-1-yl]-2-oxoethyl}-6-(morpholin-4-yl)pyrimidin-4(3H)-one |
| 2-{2-[(2S)-2-Methyl-2,3-dihydro-1H-indol-1-yl]-2-oxoethyl}-6-(4-morpholinyl)-4(1H)-pyrimidinone |
| 4(3H)-Pyrimidinone, 2-[2-[(2S)-2,3-dihydro-2-methyl-1H-indol-1-yl]-2-oxoethyl]-6-(4-morpholinyl)- |
| SAR-260301 |