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 No.
- 2136246-72-3
- Chemical 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)-
- 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)-
- CBNumber:
- CB49001363
- Molecular Formula:
- C48H47Cl2FN6O6
- Molecular Weight:
- 893.84
- MDL Number:
- MFCD34179068
- MOL File:
- 2136246-72-3.mol
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)- Properties
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 |
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)- Chemical Properties,Uses,Production
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].
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.
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)- Preparation Products And Raw materials
Raw materials
Preparation Products
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)- Suppliers
Supplier | Tel | Country | ProdList | Advantage | |
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Shanghai Yiyan Biotechnology Co. , Ltd. | 021-69985186 13611928337 | 3427709316@qq.com | China | 7979 | 58 |
Shanghai?Medlife?Pharm-Tech?Co.,?Ltd | 021-59167510 18117107507 | vip@med-life.cn | China | 4997 | 58 |
Supplier | Advantage |
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Shanghai Yiyan Biotechnology Co. , Ltd. | 58 |
Shanghai?Medlife?Pharm-Tech?Co.,?Ltd | 58 |