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).
Physicochemical Properties
| Molecular Formula | C31H31CL2FN4O4 |
| Molecular Weight | 613.5066 |
| Exact Mass | 612.171 |
| Elemental Analysis | C, 60.69; H, 5.09; Cl, 11.56; F, 3.10; N, 9.13; O, 10.43 |
| CAS # | 1309684-94-3 |
| Related CAS # | 1309684-94-3 |
| PubChem CID | 53238217 |
| Appearance | White to off-white solid powder |
| Density | 1.41±0.1 g/cm3 (20 ºC ,760 mmHg), 计算值 |
| LogP | 6.869 |
| Hydrogen Bond Donor Count | 4 |
| Hydrogen Bond Acceptor Count | 6 |
| Rotatable Bond Count | 7 |
| Heavy Atom Count | 42 |
| Complexity | 1040 |
| Defined Atom Stereocenter Count | 4 |
| SMILES | ClC1C([H])=C([H])C2=C(C=1[H])N([H])C([C@@]12C([H])(C2C([H])=C([H])C([H])=C(C=2F)Cl)C([H])(C(N([H])C2C([H])=C([H])C(C(N([H])[H])=O)=C([H])C=2OC([H])([H])[H])=O)N([H])C1([H])C([H])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H])=O |
| InChi Key | MURAVORBGFDSMA-ISKXDESKSA-N |
| 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 |
| 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 |
| Synonyms | RO-8994; RO 8994; RO8994 |
| HS Tariff Code | 2934.99.9001 |
| 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) |
Biological Activity
| Targets | MDM2 (IC50 = 5 nM); MDM2 (IC50 = 20 nM) |
| References |
[1]. Discovery of potent and selective spiroindolinone MDM2 inhibitor, RO8994, for cancer therapy. Bioorg Med Chem. 2014 Aug 1;22(15):4001-4009. |
Solubility Data
| Solubility (In Vitro) |
DMSO: 45~100 mg/mL (73.4~163.0 mM) Ethanol: ~13 mg/mL (~21.2 mM) |
| 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 |