| 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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| 250mg |
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Purity: ≥98%
Onatasertib (CC-223; CC223) is a potent, selective, and orally bioavailable mTOR (mammalian target of rapamycin) kinase inhibitor with anticancer activity. mTOR is a serine/threonine kinase that is upregulated in various tumors, and plays an important role downstream in the PI3K/AKT/mTOR signaling pathway, which is frequently dysregulated in human cancers. CC-223 demonstrated inhibition of mTORC1 (pS6RP and p4EBP1) and mTORC2 [pAKT(S473)] in cellular systems. CC-223 is selective for mTOR kinase with >200-fold selectivity over the related PI3K-α (IC50=4.0 μM). Of the PI3K related kinases tested, CC-223 shows no significant inhibition of ATR or SMG1 and inhibits DNA-PK with an IC50 value of 0.84 μM.
| Targets |
mTOR (IC50 = 16 nM); DNA-PK (IC50 = 0.84 μM); PI3K-α (IC50 = 4 μM); mTORC1; mTORC2
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| ln Vitro |
In a panel of cell lines, CC-223 inhibits both mTORC1 (S6RP and 4EBP1) and mTORC2 [AKT(S473)] markers with IC50 ranges of 27 to 184 nM for pS6RP, 120 to 1,050 nM for p4EBP1 and 11 to 150 nM for pAKT(S473), respectively. Additionally, CC-223 causes apoptosis and slows cell growth in a variety of cancer cell lines. [1]
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| ln Vivo |
In PC-3 tumor-bearing mice, CC-223 (25 mg/kg, p.o.) inhibits both mTORC1 and mTORC2. CC-223 (25 mg/kg, p.o.) also results in tumor growth inhibition by 47% to 95% in xenograft models of prostate, glioma, breast, lung, and colon. [1]
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| Enzyme Assay |
Counter screen against 246 protein kinases is outsourced and completed at a fixed CC-223 concentration (10 μM). Ephrin type-B receptor 3 kinase (EPHB3), colony stimulating factor 1 receptor tyrosine kinase (CSF1R or cFMS), and FMS-related tyrosine kinase 4 (FLT4) follow-up IC50 value determinations are contracted out to Invitrogen.
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| Cell Assay |
Compound is spotted into a 384-well plate that is not already filled using an acoustic dispenser (EDC ATS-100). Directly onto the compound-spotted plates, cells are added after being diluted to the desired density. For 72 hours, cells are permitted to grow. Utilizing Cell Titer-Glo, viability is evaluated. All data are normalized and shown as a percentage of the cells that received DMSO treatment. The GI50 and/or IC50 values of the results are then presented.
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| Animal Protocol |
Mice: Female CB17 SCID mice aged 6 to 8 weeks are s.c. inoculated with 2 106 PC-3 cells. Mice are randomized and treated once daily, twice daily, or every two days with vehicle or various doses of CC-223 at a dose volume of 5 mL/kg starting when tumors measure about 125 mm3. The morning and evening doses of the twice-daily medications are spaced apart by 10 hours. The starting volumes are the tumor volumes, which are established prior to the start of treatment. Throughout the course of the study, tumors are measured twice per week. A digital caliper is used to measure each tumor's long and short axes in millimeters. Volumes of the tumor are calculated. The cubic millimeters (mm3) used to express tumor volumes.
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| References |
| Molecular Formula |
C21H27N5O3
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| Molecular Weight |
397.47
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| Exact Mass |
397.21139
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| Elemental Analysis |
C, 63.46; H, 6.85; N, 17.62; O, 12.08
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| CAS # |
1228013-30-6
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| Related CAS # |
1228013-30-6;
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| Appearance |
Red to pink solid powder
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| SMILES |
CC(C)(C1=NC=C(C=C1)C2=CN=C3C(=N2)N(C(=O)CN3)C4CCC(CC4)OC)O
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| InChi Key |
UFKLYTOEMRFKAD-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C21H27N5O3/c1-21(2,28)17-9-4-13(10-22-17)16-11-23-19-20(25-16)26(18(27)12-24-19)14-5-7-15(29-3)8-6-14/h4,9-11,14-15,28H,5-8,12H2,1-3H3,(H,23,24)
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| Chemical Name |
3-[6-(2-hydroxypropan-2-yl)pyridin-3-yl]-5-(4-methoxycyclohexyl)-7,8-dihydropyrazino[2,3-b]pyrazin-6-one
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| Synonyms |
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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 |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.25 mg/mL (3.14 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 12.5 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: ≥ 1.25 mg/mL (3.14 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 12.5 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5159 mL | 12.5796 mL | 25.1591 mL | |
| 5 mM | 0.5032 mL | 2.5159 mL | 5.0318 mL | |
| 10 mM | 0.2516 mL | 1.2580 mL | 2.5159 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 |
| NCT02031419 | Active Recruiting |
Drug: CC-122 Drug: CC-223 |
Lymphoma, Large B-Cell, Diffuse |
Celgene | December 18, 2013 | Phase 1 |
| NCT01896323 | Completed | Drug: CC-223 Drug: Ketoconazole |
Healthy Volunteers | Celgene | July 1, 2013 | Phase 1 |
| NCT01611467 | Completed | Drug: CC-223 | Safety and Pharmacokinetics in Healthy Volunteer Subjects |
Celgene | June 1, 2012 | Phase 1 |
| NCT01177397 | Completed | Drug: CC-223 | Multiple Myeloma Glioblastoma Multiforme |
Celgene | July 20, 2010 | Phase 1 Phase 2 |
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