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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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Purity: ≥98%
RO8994, a spiroindolinone-based compound, is a novel, highly potent and selective small-molecule inhibitor of p53/MDM2 interaction with IC50 of 5 nM in a HTRF binding assay and 20 nM in a MTT proliferation assay. For the treatment of cancer, RO8994 has potential value. In contrast to solid tumors, which have a percentage of p53 deletions and/or mutations close to 50%, more than 80% of haematological malignancies have wild-type p53 at the time of diagnosis. The majority of haematological malignancies may therefore benefit from a new therapeutic approach that involves activating the p53 pathway by inhibiting its antagonistic regulator, murine double minute 2 (MDM2).
Targets |
MDM2 (IC50 = 5 nM); MDM2 (IC50 = 20 nM)
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References |
Molecular Formula |
C31H31CL2FN4O4
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Molecular Weight |
613.5066
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Exact Mass |
612.17064
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Elemental Analysis |
C, 60.69; H, 5.09; Cl, 11.56; F, 3.10; N, 9.13; O, 10.43
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CAS # |
1309684-94-3
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Related CAS # |
1309684-94-3
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Appearance |
Solid powder
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SMILES |
CC(C)(C)C[C@H]1[C@@]2([C@H]([C@@H](N1)C(=O)NC3=C(C=C(C=C3)C(=O)N)OC)C4=C(C(=CC=C4)Cl)F)C5=C(C=C(C=C5)Cl)NC2=O
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InChi Key |
MURAVORBGFDSMA-ISKXDESKSA-N
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InChi Code |
InChI=1S/C31H31Cl2FN4O4/c1-30(2,3)14-23-31(18-10-9-16(32)13-21(18)37-29(31)41)24(17-6-5-7-19(33)25(17)34)26(38-23)28(40)36-20-11-8-15(27(35)39)12-22(20)42-4/h5-13,23-24,26,38H,14H2,1-4H3,(H2,35,39)(H,36,40)(H,37,41)/t23-,24-,26+,31+/m0/s1
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Chemical Name |
(2'R,3R,3'S,5'S)-N-(4-carbamoyl-2-methoxyphenyl)-6-chloro-3'-(3-chloro-2-fluorophenyl)-5'-(2,2-dimethylpropyl)-2-oxospiro[1H-indole-3,4'-pyrrolidine]-2'-carboxamide
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Synonyms |
RO-8994; RO 8994; RO8994
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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: 45~100 mg/mL (73.4~163.0 mM)
Ethanol: ~13 mg/mL (~21.2 mM) |
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Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (3.39 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 (3.39 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 | 1.6300 mL | 8.1498 mL | 16.2997 mL | |
5 mM | 0.3260 mL | 1.6300 mL | 3.2599 mL | |
10 mM | 0.1630 mL | 0.8150 mL | 1.6300 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.
Figure 5. Weston blot analysis of p53 activation induced by compound 4 (RO8994) in SJSA osteosarcoma tumor tissue. Bioorg Med Chem . 2014 Aug 1;22(15):4001-9. td> |
Figure 7. The oral in vivo efficacy profile of 4 (RO8994) in the SJSA-1 human osteosarcoma xenograft model in nude mice. Tumor growth inhibition was observed at 1.56 mg/kg qd and tumor regression was observed at 6.25 mg/kg qd. Bioorg Med Chem . 2014 Aug 1;22(15):4001-9. td> |