Name: MD-224
Brand: BOC Sciences
Rating: 5 (1 reviews)

Size

Price

Stock

Quantity

$--

In stock

Purity

≥95%

Solubility

Soluble in DMSO

Appearance

Solid Powder

Storage

Store at 2-8°C for short term (days to weeks) or -20°C for long term (months to years)

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)pent-4-yn-1-yl)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]-4-pentyn-1-yl}carbamoyl)phenyl]-2''-oxo-1'',2''-dihydrodispiro[cyclohexane-1,2'-pyrrolidine-3',3''-indole]-5'-carboxamide; MD 224; MD224; 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]-4-pentyn-1-yl]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]-4-pentyn-1-yl]amino]carbonyl]phenyl]-1'',2''-dihydro-2''-oxodispiro[cyclohexane-1,2'-pyrrolidine-3',3''-[3H]indole]-5'-carboxamide

Density

1.49±0.1 g/cm3

InChI Key

ZLGNYFOIDAVMHY-MPKOGUQCSA-N

InChI

InChI=1S/C48H43Cl2FN6O6/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,1-2,4-6,20-24,26H2,(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)NCCCC#CC5=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. Discovery of MD-224 as a first-in-class, highly potent, and efficacious proteolysis targeting chimera murine double minute 2 degrader capable of achieving complete and durable tumor regression.

Li, Y., Yang, J., Aguilar, A., McEachern, D., Przybranowski, S., Liu, L., Yang, C.Y., Wang, M., Han, X. and Wang, S., 2018. Journal of medicinal chemistry, 62(2), pp.448-466.

Human murine double minute 2 (MDM2) protein is a primary endogenous cellular inhibitor of the tumor suppressor p53 and has been pursued as an attractive cancer therapeutic target. Several potent, nonpeptide, small-molecule inhibitors of MDM2 are currently in clinical development. In this paper, we report our design, synthesis, and evaluation of small-molecule MDM2 degraders based on the proteolysis targeting chimera (PROTAC) concept. The most promising compound (MD-224) effectively induces rapid degradation of MDM2 at concentrations <1 nM in human leukemia cells. It achieves an IC50 value of 1.5 nM in inhibition of growth of RS4;11 cells and also low nanomolar IC50 values in a panel of leukemia cell lines. MD-224 achieves complete and durable tumor regression in vivo in the RS4;11 xenograft tumor model in mice at well-tolerated dose schedules. MD-224 is thus a highly potent and efficacious MDM2 degrader and warrants extensive evaluations as a new class of anticancer agent.

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Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
It is commonly abbreviated as: C₁V₁ = C₂V₂