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Purity: ≥98%
OSI-027 (formerly known as ASP4786; AEVI006; CERC006) is a novel, potent, selective, orally bioavailable and ATP-competitive dual inhibitor of mTORC1 (mammalian target of rapamycin 1) and mTORC2 with potential anticancer activity. It exhibits more than 100-fold selectivity for mTOR over PI3Kα, PI3Kβ, PI3Kγ or DNA-PK and inhibits mTORC1/2 with IC50 values of 22 nM and 65 nM in cell-free assays. By blocking mTORC1 and mTORC2, the anticancer drug OSI-027 has the potential to have antineoplastic activity. In cellular assays, OSI-027 blocks downstream signaling by preventing mTORC1 and mTORC2 substrates like AKT, PRAS40, and S6K1 from being phosphorylated. VEGF secretion in vitro and tumor xenograft growth in vivo are both reduced by OSI-27's dual inhibition of the mTOR kinase complexes mTORC1 and mTORC2.
| Targets |
mTOR (IC50 = 4 nM); mTORC1 (IC50 = 22 nM); mTORC2 (IC50 = 65 nM); PI3K-γ (IC50 = 0.42 μM); PI3K-α (IC50 = 1.3 μM); DNA-PK (IC50 = 1 μM); Autophagy
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| ln Vitro |
OSI-027 shows the selective and ATP competitive inhibition activities against mTORC1 and mTORC2 with IC50 of 22 nM and 65 nM, respectively. Additionally, OSI-027 blocks phospho-4E-BP1 mTOR signaling in cell-based assays with an IC50 of 1 μM . [1] In a dose-dependent manner, OSI-027 displays anti-proliferative activities against a number of acute leukemia cell lines of myeloid/megakaryocytic origin, including U937, KG-1, KBM-3B, ML-1, HL-60, and MEG-01 cells. [2] A recent study demonstrates that OSI-027's effective inhibition of mTORC1/2 inhibits the phosphorylation of Akt (S473) and cell proliferation in breast cancer cells. [3]
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| ln Vivo |
In GEO colorectal xenograft, OSI-027 (65 mg/kg) inhibits the phosphorylation of 4E-BP1, Akt, and S6 as well as mTORC1 and mTORC2 effectors. Additionally, OSI-027 potently inhibits tumor growth more than rapamycin does when mTORC1 and mTORC2 are both inhibited. [1]
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| Enzyme Assay |
At a concentration of 100 mM ATP, the SelectScreen profiling service runs assays on a panel of 40 additional recombinant kinases, including both protein and lipid kinases. The Ambit KinomeScan platform is used to test a large panel of kinases at a single concentration of OSI-027 or OXA-01 (3 M) in order to determine the percent inhibition of each kinase or mutant variant.
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| Cell Assay |
To study the effect of drug treatment on cellular signaling, Ovcar-3 cells are plated in normal growth medium. After 24 hours, serum is removed and cells are serum-starved overnight. In DMSO, rapamycin, OSI-027, and OXA-01 are dissolved before being added to cells at various concentrations. After two hours of incubation, cells are growth factor stimulated for 3 to 5 minutes with 10 ng/mL Insulin, rinsed with cold PBS, and then lysed[1].
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| Animal Protocol |
Mice: In xenograft models, cells are taken, injected subcutaneously (s.c.) into the right flank of nu/nu CD-1 mice, and tumor development is examined. Tumors are collected at 2, 8, and 24 hours in mice with GEO xenografts that have received a 12-day treatment with OSI-027 (65mg/kg) or vehicle. There are calculations for both tumor growth inhibition and regression.
Rats: Male BN rats, male Lew-Tg(CAG-EGFP)YsRrrc rats, male Lew-Tg(YsRrrc)YsRrrc rats, and female Lewis rats free of specific pathogens are all used. We carry out orthotopic LT. There was no use of antibiotics. Within 30 minutes of LT, each recipient receives a dorsal penile vein infusion of freshly prepared splenocytes (4108, suspended in 500 L PBS) from Lew-Tg YsRrrc rats. RAPA (1 mg/kg), OSI-027 (1 mg/kg), and control (equal amounts of vehicle) groups are divided into three experimental groups of LTx-aGVHD model rats. From day 7 to day 15, treatments are given via the vena caudalis.
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| References | |
| Additional Infomation |
4-[4-amino-5-(7-methoxy-2-indolylidene)-1H-imidazo[5,1-f][1,2,4]triazin-7-yl]-1-cyclohexanecarboxylic acid is a member of indoles.
OSI-027 has been used in trials studying the treatment of Any Solid Tumor or Lymphoma. mTOR Kinase Inhibitor CERC-006 is an orally bioavailable mammalian target of rapamycin (mTOR) kinase inhibitor, with potential antineoplastic activity. Upon oral administration, mTOR kinase inhibitor CERC-006 binds to and inhibits both the raptor-mTOR (TOR complex 1 or TORC1) and the rictor-mTOR (TOR complex 2 or TORC2) complexes of mTOR, which may result in tumor cell apoptosis and a decrease in tumor cell proliferation. mTOR is a serine/threonine kinase that is upregulated in some tumors and plays an important role downstream in the PI3K/Akt/mTOR signaling pathway. |
| Molecular Formula |
C21H22N6O3
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| Molecular Weight |
406.437783718109
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| Exact Mass |
406.175
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| Elemental Analysis |
C, 62.06; H, 5.46; N, 20.68; O, 11.81
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| CAS # |
936890-98-1
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| Related CAS # |
1187559-64-3 (calcium);1187559-66-5 (sodium);1187559-73-4 (potassium);936890-98-1 (free acid);
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| PubChem CID |
135398516
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.6±0.1 g/cm3
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| Boiling Point |
591.4±60.0 °C at 760 mmHg
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| Flash Point |
311.5±32.9 °C
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| Vapour Pressure |
0.0±3.6 mmHg at 25°C
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| Index of Refraction |
1.788
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| LogP |
-0.37
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
30
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| Complexity |
630
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| Defined Atom Stereocenter Count |
0
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| SMILES |
NC1=NC=NN2C1=C(C1=CC3C=CC=C(C=3N1)OC)N=C2[C@@H]1CC[C@@H](C(=O)O)CC1
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| InChi Key |
JROFGZPOBKIAEW-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C21H22N6O3/c1-30-15-4-2-3-13-9-14(25-16(13)15)17-18-19(22)23-10-24-27(18)20(26-17)11-5-7-12(8-6-11)21(28)29/h2-4,9-12,25H,5-8H2,1H3,(H,28,29)(H2,22,23,24)
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| Chemical Name |
4-[4-amino-5-(7-methoxy-1H-indol-2-yl)imidazo[5,1-f][1,2,4]triazin-7-yl]cyclohexane-1-carboxylic acid
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| Synonyms |
OSI027; OSI 027; OSI-027
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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: ~18 mg/mL (44.3 mM)
Water: <1 mg/mL Ethanol: <1 mg/mL |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.15 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 25.0 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: 2.5 mg/mL (6.15 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 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: 1% DMSO+30% polyethylene glycol+1% Tween 80: 30mg/mL |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4604 mL | 12.3019 mL | 24.6039 mL | |
| 5 mM | 0.4921 mL | 2.4604 mL | 4.9208 mL | |
| 10 mM | 0.2460 mL | 1.2302 mL | 2.4604 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 |
| NCT00698243 | Completed | Drug: OSI-027 | Any Solid Tumor or Lymphoma | Astellas Pharma Inc | June 2008 | Phase 1 |
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