MD-224


Catalog No. size PriceQuantity
M6980-2 2mg solid $106
M6980-10 10mg solid $458

Description

Cas:2136247-12-4 (free base)

Product Information:

MD-224 is a First-in-Class, Highly Potent, and Efficacious Proteolysis Targeting Chimera Murine Double Minute 2 Degrader Capable of Achieving Complete and Durable Tumor Regression. 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.

 

Chemical Formula: C48H43Cl2FN6O6

 

Exact Mass: 888.2605

 

Molecular Weight: 889.8064

 

Elemental Analysis: C, 64.79; H, 4.87; Cl, 7.97; F, 2.14; N, 9.44; O, 10.79

 

Synonym:

 

MD 224

MD224

 

Chemical Name: 

(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

 

InChi Key: 

ZLGNYFOIDAVMHY-MPKOGUQCSA-N

 

InChi Code: 

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

 

Smiles Code:

FC1=C(Cl)C=CC=C1[C@@H]2[C@@]3(C(C=CC(Cl)=C4)=C4NC3=O)C5(CCCCC5)N[C@H]2C(NC6=CC=C(C(NCCCC#CC7=C(CN(C8C(NC(CC8)=O)=O)C9=O)C9=CC=C7)=O)C=C6)=O

 

 

Technical Data:

 

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO

Shelf Life: >3 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

 

In Vitro:

MD-224 (1-30 nM; 2 hours) effectively induces depletion of MDM2 protein and concurrently accumulation of p53 protein in a dose-dependent manner in RS4;11 cells.

MD-224 (30 nM; 6 hours) is more potent than MI-1061 in induction of transcriptional upregulation of these p53 target genes but have no effect on TP53 itself in RS4;11 cells.

MD-224 (0.001-1 μM; 24 hours) induces robust apoptosis at ≤10 nM in a dose-dependent manner upon a 24 hours treatment.

 

 

References:

 

1.Li Y, Yang J, Aguilar A, et al. 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. J Med Chem. 2019;62(2):448‐466. doi:10.1021/acs.jmedchem.8b00909.

 

Products are for research use only. Not for human use.

 

 

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