MD-222

Size	Price	Stock	Quantity
--	$--	In stock

Size

Price

Stock

Quantity

$--

In stock

Purity

99%

IUPACName

(3'R,4'S,5'R)-6''-chloro-4'-(3-chloro-2-fluorophenyl)-N-(4-((5-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)pentyl)carbamoyl)phenyl)-2''-oxodispiro[cyclohexane-1,2'-pyrrolidine-3',3''-indoline]-5'-carboxamide

Synonyms

(3'R,4'S,5'R)-6''-Chloro-4'-(3-chloro-2-fluorophenyl)-N-[4-({5-[2-(2,6-dioxo-3-piperidinyl)-1-oxo-2,3-dihydro-1H-isoindol-4-yl]pentyl}carbamoyl)phenyl]-2''-oxo-1'',2''-dihydrodispiro[cyclohexane-1,2'-pyrrolidine-3',3''-indole]-5'-carboxamide; MD 222; MD222; 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)-; (3'R,4'S,5'R)-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''-oxodispiro[cyclohexane-1,2'-pyrrolidine-3',3''-[3H]indole]-5'-carboxamide

Density

1.46±0.1 g/cm3

InChI Key

RRSNDVCODIMOFX-MPKOGUQCSA-N

InChI

InChI=1S/C48H47Cl2FN6O6/c49-29-16-19-34-36(25-29)54-46(63)48(34)39(32-12-8-13-35(50)40(32)51)41(56-47(48)22-4-2-5-23-47)44(61)53-30-17-14-28(15-18-30)42(59)52-24-6-1-3-9-27-10-7-11-31-33(27)26-57(45(31)62)37-20-21-38(58)55-43(37)60/h7-8,10-19,25,37,39,41,56H,1-6,9,20-24,26H2,(H,52,59)(H,53,61)(H,54,63)(H,55,58,60)/t37?,39-,41+,48+/m0/s1

Canonical SMILES

C1CCC2(CC1)C3(C(C(N2)C(=O)NC4=CC=C(C=C4)C(=O)NCCCCCC5=C6CN(C(=O)C6=CC=C5)C7CCC(=O)NC7=O)C8=C(C(=CC=C8)Cl)F)C9=C(C=C(C=C9)Cl)NC3=O

1. Simple Structural Modifications Converting a Bona fide MDM2 PROTAC Degrader into a Molecular Glue Molecule: A Cautionary Tale in the Design of PROTAC Degraders

Angelo Aguilar, Yangbing Li, Shaomeng Wang, Jiuling Yang, Chao-Yie Yang, Zhaomin Liu J Med Chem . 2019 Nov 14;62(21):9471-9487. doi: 10.1021/acs.jmedchem.9b00846.

Inducing protein degradation by proteolysis targeting chimeras (PROTACs) has gained tremendous momentum for its promise to discover and develop new therapies. Based upon our previously reported PROTAC MDM2 degraders, we have designed and synthesized additional analogues. Surprisingly, we found that simple structural modifications of MD-222, a bona fide MDM2 PROTAC degrader, converts it into a "molecular glue", as exemplified byMG-277.MG-277induces only moderate MDM2 degradation and fails to activate wild-type p53 but is highly potent in inhibition of tumor cell growth in a p53-independent manner. Our mechanistic investigation established thatMG-277is not a PROTAC MDM2 degrader but instead works as a molecular glue, inducing degradation of a translation termination factor, GSPT1 to achieve its potent anticancer activity. Our study provides the first example that simple structural modifications can convert a bona fide PROTAC degrader into a molecular glue compound, which has a completely different mechanism of action.

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* Our calculator is based on the following equation:
Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
It is commonly abbreviated as: C₁V₁ = C₂V₂