| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
| Targets |
PI3K
Recilisib modulates the PI3K/Akt/mTOR signaling pathway. It is described as a selective PI3Kδ (phosphoinositide 3-kinase delta) inhibitor that blocks PI3Kδ kinase activity, thereby inhibiting downstream AKT/mTOR signaling and suppressing B-cell proliferation and immune responses. The compound activates AKT and PI3K activities in cells. Its primary targets are Akt and PI3K. The radioprotective mechanism appears to involve the prevention of both p53-dependent and p53-independent radiation-induced apoptosis. Through the activation of the AKT pathway, it lessens radiation damage. Recilisib treatment in combination with radiation also alters the MAPK signaling pathway. |
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| ln Vitro |
Recilisib sodium (up to 50 μM) exhibits a consistent pattern of cells throughout the cell cycle, with a slight decrease in the proportion of cells in S-phase at this concentration. Recilisib Sodium (100 μM) does not cause cell death when administered continuously. The ability of human bone marrow cells to form colonies is not inhibited by recilisib sodium treatment. At each of the three IR doses, recilisib sodium offers human bone marrow cells dose-dependent protection. In HFL cells, recilisib sodium stimulates AKT and GSKα/β phosphorylation. In HFL-1 cells and murine bone marrow cells, recilisib sodium boosts PI3K activity in response to radiation exposure. The MAPK signaling pathway is altered by recilisib sodium treatment in conjunction with radiation[1].
In vitro, Recilisib Sodium increases PI3K activity in HFL-1 cells and murine bone marrow cells in response to radiation exposure. It stimulates the phosphorylation of AKT and GSK3α/β in HFL cells. At concentrations up to 50 µM, Recilisib Sodium shows a normal distribution of cells throughout the cell cycle, with a slight reduction in the number of cells in S-phase at 50 µM. Continuous exposure at 100 µM does not result in cell death, and the compound does not inhibit the colony forming potential of human bone marrow cells, indicating low myelotoxicity. Recilisib Sodium treatment in combination with radiation alters the MAPK signaling pathway. |
| ln Vivo |
In mice, recilisib sodium (500 mg/kg) significantly accelerates the recovery and differentiation of early myeloid progenitor cells from the bone marrow. When combined with radiation, Recilisib Sodium lowers the number of CFUs in mice, but mice treated with Recilisib Sodium consistently retain the ability to form differentiated colonies. The progenitor cell population in Recilisib Sodium-treated mice is never completely depleted by radiation exposure[1].
In vivo, Recilisib Sodium (500 mg/kg) significantly increases the rate of recovery and differentiation of primitive bone marrow myeloid progenitor cells in mice. Recilisib Sodium-treated mice consistently retain a capability to form differentiated colonies, and their progenitor cell population is never completely depleted by radiation exposure. Recilisib Sodium in combination with radiation reduces CFU numbers in mice, but treated mice retain the ability to form differentiated colonies. The compound has been studied as both a prophylactic (use prior to radiation exposure) and therapeutic (after exposure to radiation) drug. |
| Enzyme Assay |
In PI3-kinase assays, freshly isolated murine bone marrow cells or exponentially growing HFL-1 cells are exposed to increasing concentrations of Recilisib sodium for two hours before being exposed to 10 Gy IR. After being lysed in HEPES pH 7.5 lysis buffer, these cells are then put back in the incubator for two to twenty-four hours. An anti-PI3 Kinas polyclonal antibody is used to immunoprecipitate PI-3K for two hours at room temperature. Immunoprecipitates are incubated with Protein A/G PLUS-Agarose for 8–16 hours at 4°C, and the resulting immunoprecipitates are then washed with the kinase buffer (20 mM Tris pH 7.5, 1 mM EGTA, 10 mM MgCl2, 2 mM DTT, 0.01% NP-40) once and twice, respectively. In the kinase buffer (60 µL per sample), L--Phosphatidylinositol (12.5 mM) and ATP (10 µM) are added. The mixture is then incubated at 30°C for 30 minutes. 100 µL of 1N HCl is added to stop the reaction, and 200 µL of CHCl3/CH3OH (1:1) is added to extract the product. The lower organic phases containing phospholipids are dried at 27°C for two hours after being vortexed and centrifuged with the extracted samples. After being dried, the samples are reconstituted in 10 µL of PI-4-P standard (0.5 mL CHCl3, 0.5 mL CH3OH, 2.5 µL HCl), and then spots are applied to TLC plates (VWR). Thin layer chromatography is performed on the spotted plate using CHCl3, CH3OH, and NH4OH (40:40:15). The TLC plate is dried before autoradiography is performed.
For non-cellular enzyme/receptor binding assays, typical procedures involve assessing PI3K activity via kinase assays using purified enzyme preparations. The inhibition or activation of PI3K isoforms is measured. IC50 values are determined using standard radioactive or luminescent kinase activity detection methods with varying concentrations of the compound. Given that Recilisib is a PI3Kδ inhibitor, binding affinity can be assessed through competitive binding assays using radiolabeled ligands or through surface plasmon resonance (SPR) to measure direct binding kinetics to the purified PI3Kδ enzyme. |
| Cell Assay |
For cytotoxicity tests, cells (1.0×105 cells/mL HPGM) are exposed to different concentrations of the drug Recilisib Sodium or a control substance for two or twenty-four hours. The cells are cleaned and plate into gridded dishes for methocult. Using an Olympus IMT-2 microscope, 14 days after plating, the total number of colony forming units (CFUs) was counted.
For in vitro cytotoxicity and efficacy assays, cells such as HFL-1 fibroblasts or murine bone marrow cells are cultured in appropriate media. Cells (e.g., 1.0×10⁵ cells/mL HPGM) are treated with various concentrations of Recilisib Sodium or vehicle, with or without radiation exposure for 2 or 24 hours. The cells are then washed and plated into methocult using gridded dishes. The total number of colony forming units (CFUs) is determined 14 days post-plating by microscopic observation. Cell cycle distribution is analyzed via flow cytometry after propidium iodide staining. For cell viability, MTT or similar assays can be performed after treatment. |
| Animal Protocol |
In vivo animal studies are typically conducted in mice. Recilisib Sodium is administered at a dose of 500 mg/kg. The compound can be formulated for in vivo administration using 10% DMSO + 90% Corn Oil at a concentration of 2.5 mg/mL (7.42 mM). Animals are exposed to ionizing radiation, and the recovery and differentiation of primitive bone marrow myeloid progenitor cells are assessed. The protective effects on bone marrow are evaluated by measuring CFU numbers and progenitor cell populations. The compound has been evaluated in both prophylactic and therapeutic dosing regimens.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of Recilisib include solubility in DMSO (50 mg/mL, 148.46 mM). For in vivo formulation, 10% DMSO + 90% Corn Oil at 2.5 mg/mL (7.42 mM) is recommended. The powder is stable at -20°C for 3 years and in solvent at -80°C for 1 year. Working solutions should be prepared and used immediately. The molecular weight is 336.79. It is soluble in DMSO with sonication recommended. In vivo formulations may vary and should be modified based on specific experimental conditions.
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| Toxicity/Toxicokinetics |
In preclinical studies, Recilisib has shown favorable safety and good tolerability. It does not result in cell death even with continuous exposure at 100 µM. It does not inhibit the colony forming potential of human bone marrow cells, indicating low myelotoxicity. The radioprotective mechanism appears to involve prevention of p53-dependent and p53-independent radiation-induced apoptosis. No significant toxicity has been reported in preclinical models at efficacious doses.
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| References | |
| Additional Infomation |
Recilisib is also known by the aliases ON 01210 and Ex-RAD. It is a radioprotectant that enhances cell survival signals and limits oxidative stress and DNA injury. It continues to serve as a promising investigational compound in radioprotective research. Onconova Therapeutics has tested it in Phase I clinical trials to treat acute radiation syndrome. It has been evaluated for use in acute radiation syndrome, supportive cancer therapy, and tissue-protection applications.
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| Molecular Formula |
C₁₆H₁₃CLO₄S
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|---|---|
| Molecular Weight |
336.79
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| Exact Mass |
336.022
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| Elemental Analysis |
C, 57.06; H, 3.89; Cl, 10.53; O, 19.00; S, 9.52
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| CAS # |
334969-03-8
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| Related CAS # |
Recilisib sodium;922139-31-9
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| PubChem CID |
9884220
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| Appearance |
White to off-white solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
607.8±55.0 °C at 760 mmHg
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| Flash Point |
321.4±31.5 °C
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| Vapour Pressure |
0.0±1.8 mmHg at 25°C
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| Index of Refraction |
1.639
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| LogP |
3.84
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
22
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| Complexity |
493
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C(O)C1=CC=C(/C=C/S(=O)(CC2=CC=C(Cl)C=C2)=O)C=C1
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| InChi Key |
KBEKQQJUNVQLDZ-MDZDMXLPSA-N
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| InChi Code |
InChI=1S/C16H13ClO4S/c17-15-7-3-13(4-8-15)11-22(20,21)10-9-12-1-5-14(6-2-12)16(18)19/h1-10H,11H2,(H,18,19)/b10-9+
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| Chemical Name |
Benzoic acid, 4-((1E)-2-(((4-chlorophenyl)methyl)sulfonyl)ethenyl)-
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| Synonyms |
ON-01210; ON01210; Recilisib; 334969-03-8; ON 01,210; Recilisib [USAN]; Recilisib [USAN:INN]; ON 01210; Recilisib Free Base
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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: 35.7~67 mg/mL (106 mM~198.9 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (6.18 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.9692 mL | 14.8460 mL | 29.6921 mL | |
| 5 mM | 0.5938 mL | 2.9692 mL | 5.9384 mL | |
| 10 mM | 0.2969 mL | 1.4846 mL | 2.9692 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.
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