| Size | Price | Stock | Qty |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg | |||
| Other Sizes |
Purity: ≥98%
| 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)
SAR260301 targets the Class I phosphatidylinositol-3-kinase (PI3K) β isoform. PI3Kβ is a lipid kinase that plays a critical role in the PI3K/AKT/mTOR signaling pathway, which regulates cell growth, proliferation, and survival. SAR260301 is a potent, selective, and ATP-competitive inhibitor of PI3Kβ, with an IC50 of 52 nM. By inhibiting PI3Kβ, SAR260301 blocks the activation of AKT and downstream signaling pathways, leading to reduced cell proliferation and survival, particularly in PTEN-deficient tumors. |
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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].
In vitro, SAR260301 is a potent and selective inhibitor of PI3Kβ. It has an IC50 of 52 nM for PI3Kβ in a TR-FRET assay. The compound displays improved physicochemical and in vitro pharmacokinetic properties. Its selectivity for PI3Kβ over other PI3K isoforms has been confirmed. These in vitro studies establish SAR260301 as a potent and selective PI3Kβ inhibitor with potential antitumor activity. |
| 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].
In vivo, SAR260301 is an orally bioavailable PI3Kβ inhibitor that is being investigated for the treatment of PTEN-deficient tumors. PTEN is a tumor suppressor that negatively regulates the PI3K pathway, and its loss leads to hyperactivation of PI3K signaling. SAR260301 has demonstrated antitumor activity in preclinical models of PTEN-deficient cancers. However, specific in vivo protocols and results are not detailed in standard product descriptions. |
| 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.
In vitro enzyme assays for SAR260301 measure its inhibition of PI3Kβ activity. A TR-FRET (time-resolved fluorescence resonance energy transfer) assay is commonly used. The enzyme is incubated with a substrate and ATP in the presence of varying concentrations of the compound. The inhibition of the kinase activity is measured, and the IC50 is determined from the dose-response curve. For SAR260301, the IC50 is 52 nM. Selectivity is assessed by testing the compound against a panel of other PI3K isoforms and kinases. |
| 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].
In vitro cell-based assays for SAR260301 are used to study its effects on PI3K/AKT signaling and cancer cell biology. Cancer cells, particularly those with PTEN deficiency, are treated with SAR260301. The phosphorylation of AKT and its downstream targets is measured by Western blotting. Cell proliferation and survival are assessed using assays such as MTT or CellTiter-Glo. These assays confirm the compound's activity as a PI3Kβ inhibitor and its antiproliferative effects. |
| 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.
In vivo animal experiments for SAR260301 would be conducted in xenograft models of PTEN-deficient tumors. In a typical study, immunodeficient mice are implanted with human tumor cells and treated with SAR260301 orally. Tumor growth is monitored, and the compound's ability to inhibit tumor growth is assessed. These studies would provide evidence for the in vivo efficacy of SAR260301. However, specific protocols are not detailed. |
| ADME/Pharmacokinetics |
SAR260301 has a molecular weight of 354.40 g/mol and a molecular formula of C19H22N4O3. It has a CAS number of 1260612-13-2. It is a solid compound. For storage, it is recommended to keep the powder at -20°C. Detailed pharmacokinetic properties such as absorption, distribution, metabolism, and excretion (ADME) have been characterized. SAR260301 is orally bioavailable.
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| Toxicity/Toxicokinetics |
Detailed toxicity data for SAR260301 is not provided in standard product descriptions. As a research compound, its toxicity profile has not been extensively characterized. SAR260301 is a PI3Kβ inhibitor, and its toxicity would be related to its effects on PI3K signaling in normal tissues. However, comprehensive toxicological studies have not been reported. As with all research chemicals, standard laboratory safety precautions should be followed.
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| References |
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| Additional Infomation |
SAR260301, a PI3K-β inhibitor, is an orally bioavailable class I phosphatidylinositol 3-kinase (PI3K) β subtype inhibitor with potential antitumor activity. SAR260301 selectively inhibits PI3K-β kinase activity in the PI3K/Akt/mTOR pathway, potentially leading to apoptosis and inhibiting growth in tumor cells expressing PI3K-β and/or lacking phosphatase and tensin homolog (PTEN). Dysregulation of the PI3K/Akt/mTOR pathway is common in solid tumors, leading to tumor cell proliferation, increased survival, and resistance to chemotherapy and radiotherapy. PI3K-β is the p110-β catalytic subunit of class I PI3K. PTEN is a tumor suppressor protein and a negative regulator of PI3K activity, frequently mutated in various cancer cells. By specifically targeting class I PI3Kβ, this drug may be more effective and less toxic than pan-PI3K inhibitors.
SAR260301 is a research compound and is not approved for any clinical or therapeutic use. It is a potent, selective, and orally bioavailable inhibitor of PI3Kβ. It is an ATP-competitive inhibitor with an IC50 of 52 nM for PI3Kβ. SAR260301 is being investigated for the treatment of PTEN-deficient tumors. Its mechanism of action involves inhibiting PI3Kβ, thereby blocking the PI3K/AKT/mTOR signaling pathway and reducing tumor cell growth and survival. |
| Molecular Formula |
C19H22N4O3
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|---|---|
| Molecular Weight |
354.402984142303
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| Exact Mass |
354.169
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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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| PubChem CID |
135565159
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| Appearance |
white solid powder
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| Density |
1.4±0.1 g/cm3
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| Index of Refraction |
1.683
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| LogP |
2.26
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
26
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| Complexity |
639
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| Defined Atom Stereocenter Count |
1
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| SMILES |
O=C1N=C(CC(N2[C@@H](C)CC3=C2C=CC=C3)=O)NC(N4CCOCC4)=C1
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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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