| Identification | Back Directory | [Name]
Dispiro[cyclohexane-1,2'-pyrrolidine-3',3''-[3H]indole]-5'-carboxamide, 6''-chloro-4'-(3-chloro-2-fluorophenyl)-N-[4-[[[5-[2-(2,6-dioxo-3-piperidinyl)-2,3-dihydro-1-oxo-1H-isoindol-4-yl]pentyl]amino]carbonyl]phenyl]-1'',2''-dihydro-2''-oxo-, (3'R,4'S,5'R)- | [CAS]
2136246-72-3 | [Synonyms]
MD-222
Dispiro[cyclohexane-1,2'-pyrrolidine-3',3''-[3H]indole]-5'-carboxamide, 6''-chloro-4'-(3-chloro-2-fluorophenyl)-N-[4-[[[5-[2-(2,6-dioxo-3-piperidinyl)-2,3-dihydro-1-oxo-1H-isoindol-4-yl]pentyl]amino]carbonyl]phenyl]-1'',2''-dihydro-2''-oxo-, (3'R,4'S,5'R)- | [Molecular Formula]
C48H47Cl2FN6O6 | [MDL Number]
MFCD34179068 | [MOL File]
2136246-72-3.mol | [Molecular Weight]
893.84 |
| Chemical Properties | Back Directory | [density ]
1.46±0.1 g/cm3(Predicted) | [storage temp. ]
-20°C, away from moisture | [solubility ]
DMSO : 200 mg/mL (223.76 mM; Need ultrasonic) | [form ]
Solid | [pka]
10.73±0.40(Predicted) | [color ]
White to off-white |
| Hazard Information | Back Directory | [Uses]
MD-222 is the first-in-class highly potent PROTAC degrader of MDM2. MD-222 consists of ligands for Cereblon and MDM2. MD-222 induces rapid degradation of the MDM2 protein and activation of wild-type p53 in cells. MD-222 has anticancer effects[1][2]. | [Biological Activity]
MD-222 is the first-in-class highly potent PROTAC degrader of MDM2. MD-222 induces rapid degradation of the MDM2 protein and activation of wild-type p53 in cells. MD-222 has anticancer effects[1][2].
MD-222 (1-30 nM; 1-2 hours) treatment shows very effective in reducing the levels of MDM2 protein and increasing the levels of p53 in a time- and dose-dependent manner in RS4;11 and RS4;11/IRMI-2 cells[1]. MD-222 (30-100 nM; 6 hours) is effective in increasing the expression of several p53-targeted genes, such as MDM2, CDKN1A, and PUMA in RS4;11 cells, indicating strong activation of p53[2]. MD-222 (4 days) shows cell growth inhibitory activity in RS4;11 cells with an IC50 of 5.5 nM, and has no effect on RS4;11/IRMI-2, MDA-MB-231 and MDA-MB-468 cells[1]. | [IC 50]
MDM2 | [References]
[1]. Jiuling Yang, et al. Simple Structural Modifications Converting a Bona fide MDM2 PROTAC Degrader into a Molecular Glue Molecule: A Cautionary Tale in the Design of PROTAC Degraders. J Med Chem. 2019 Nov 14;62(21):9471-9487. [2]. Li Y, et al. Discovery of MD-224 as a First-in-Class, Highly Potent, and Efficacious Proteolysis TargetingChimera Murine Double Minute 2 Degrader Capable of Achieving Complete and Durable TumorRegression. J Med Chem. 2019 Jan 24;62(2):448-466. |
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