| Size | Price | Stock | Qty |
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| 10mg |
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Purity: ≥98%
SAR260301 is potent, orally bioavailable and selective Class I phosphatidylinositol-3-kinase (PI3K)β specific inhibitor with an IC50 of 52 nM for PI3Kβ. PTEN-deficient tumors, SAR260301 is being researched. SAR260301 showed enhanced physicochemical and in vitro pharmacokinetic characteristics. Further preclinical research on SAR260301 is necessary in light of its significant in vivo activity in a mouse UACC-62 xenograft model.
| Targets |
PI3Kβ (IC50 = 23 nM); PI3Kδ (IC50 = 468 nM); PI3Kα (IC50 = 1539 nM); PI3Kγ (IC50 = 10000 nM); Vps34 (IC50 = 183 nM); PI3KC2γ (IC50 = 3812 nM); pAkt (IC50 = 49 nM); DNA-PK (IC50 = 2000 nM)
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| ln 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]. SAR260301 has an IC50 of 196 nM and inhibits PI3Kβ-dependent proliferation/viability in low serum conditions in the MEF-3T3-myr-p110β mechanistic model. SAR260301 is inactive in these conditions in PC3 cells at concentrations up to 10 μM, despite target engagement, in low and high serum conditions in LNCaP cells with IC50 values of 2.9 and 5.0 μM, respectively, in PTEN-deficient human prostate tumor cells. Despite some cell death induction at 10 μM, SAR260301 at 3 or 10 μM inhibits PC3 cell proliferation in low serum conditions after prolonged treatment. A cytostatic effect is achieved for 14 days. 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].
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| ln 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; there are no toxicity symptoms and no weight loss. After taking SAR-260301 orally, pAkt-S473 showed sustained target inhibition (≥50%) for at least 7 hours. SAR-260301 has a moderate terminal elimination half-life (1/2=0.87 h, 1.4 h, 2.5 h, 0.87h, 6.9 h, and 4.5 h for female SCID mice, mice (10 mg/kg, po), mice (100 mg/kg, po), female nude rats, mice (3 mg/kg, iv), rats (10 mg/kg, po), and male beagle dogs)[1].
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| Enzyme Assay |
Half-maximal inhibitory concentrations (IC50) are determined using a luminescence-based assay with some minor modifications. Briefly, serial dilutions of compounds are dissolved in assay buffer (100 mM Tris-acetate pH 7.5, 40 mM NaCl and 10 mM Mg(OAc)2 containing 0.005% Tween-20 and 2 mM dithiothreitol (DTT). Upon addition of MTH1 recombinant protein (final concentration 2 nM), plates are incubated on a plate shaker for 15 min at room temperature. After addition of the substrate dGTP (final concentration 100 µM), 8-oxo-dGTP (final concentration 13.2 µM), or 2-OH-dATP (final concentration 8.3 µM) the generation of pyrophosphate (PPi) as a result of nucleotide triphosphate hydrolysis by MTH1 is monitored over a time course of 15 min using the PPi Light Inorganic Pyrophosphate Assay kit. IC50 values are determined by fitting a dose-response curve to the data points using nonlinear regression analysis using the GraphPad Prism software.
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| Cell Assay |
Cell proliferation is measured by quantifying intracellular ATP using CellTiter-Glo kit. Single or combined agents, such as SAR260301, are applied to cells seeded into 96-well black microplates in complete medium and left on the cells for 96 hours[2].
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| Animal Protocol |
Mice: SAR-260301 is evaluated for its antitumor effects in UACC-62 melanoma subcutaneous xenografts in SCID mice. Before beginning treatment, tumors are allowed to grow to at least 150 mm3, and throughout the course of the procedure, tumor volume is monitored frequently. To facilitate sustained pathway inhibition and enable comparison with the study carried out in the PC3 model, mice are administered SAR-260301 orally on a bidaily (BID) schedule at a dose of 150 mg/kg.
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| References |
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| Molecular Formula |
C19H22N4O3
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|---|---|
| Molecular Weight |
354.402984142303
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| Exact Mass |
354.16919
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| Elemental Analysis |
C, 64.39; H, 6.26; N, 15.81; O, 13.54
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| CAS # |
1260612-13-2
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| Related CAS # |
1260612-13-2
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| Appearance |
white solid powder
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| SMILES |
C[C@H]1CC2=CC=CC=C2N1C(=O)CC3=NC(=CC(=O)N3)N4CCOCC4
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| InChi Key |
UAXHPOBBKRWJGA-ZDUSSCGKSA-N
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| InChi Code |
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
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| Chemical Name |
2-[2-[(2S)-2-methyl-2,3-dihydroindol-1-yl]-2-oxoethyl]-4-morpholin-4-yl-1H-pyrimidin-6-one
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| Synonyms |
SAR260301; SAR 260301; SAR260301
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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 |
| 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) |
DMSO: ~125 mg/mL (~352.7 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.87 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 20.8 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: ≥ 2.08 mg/mL (5.87 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 20.8 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: ≥ 2.08 mg/mL (5.87 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 | 2.8217 mL | 14.1084 mL | 28.2167 mL | |
| 5 mM | 0.5643 mL | 2.8217 mL | 5.6433 mL | |
| 10 mM | 0.2822 mL | 1.4108 mL | 2.8217 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 |
| NCT01673737 | Completed | Drug: SAR260301 Drug: Vemurafenib |
Neoplasm Malignant | Sanofi | August 2012 | Phase 1 |
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