Milademetan tosylate

WARNING: This product is for research use only, not for human or veterinary use.

Description:Milademetan, also known as DS-3032b or DS-3032, is a potent and selective MDM2 inhibitor with potential antineoplastic activity. Upon oral administration, MDM2 inhibitor DS-3032b binds to, and prevents the binding of MDM2 protein to the transcriptional activation domain of the tumor suppressor protein p53. By preventing this MDM2-p53 interaction, the proteosome-mediated enzymatic degradation of p53 is inhibited and the transcriptional activity of p53 is restored. This results in the restoration of p53 signaling and leads to the p53-mediated induction of tumor cell apoptosis.

Price and Availability

DS-3032b tosylate is not in stock, but may be available through custom synthesis. For cost-effective reason, minimum 1 gram order is requested. The product will be characterized by NMR, HPLC and MS analysis. Purity (HPLC) is usually >98%. CoA, QC data, MSDS will be provided when product is successfully made. The estimated lead time is 2-3 months. Please send email to sales@medkoo.com to inquire quote.

Chemical Structure

Theoretical Analysis

MedKoo Cat#: 206063Name: Milademetan tosylateCAS#: 1398569-75-9(tosylate)Chemical Formula: C37H42Cl2FN5O7SExact Mass: Molecular Weight: 790.73Elemental Analysis: C, 56.20; H, 5.35; Cl, 8.97; F, 2.40; N, 8.86; O, 14.16; S, 4.05

Related CAS #:1398568-47-2 (free base)1398569-75-9(tosylate)2095625-97-9 (tosylate hydrate)Milademetan HCl

Synonym:DS3032b; DS-3032b; DS 3032b; DS3032; DS-3032; DS 3032; DS-3032b tosylate; Milademetan tosylate

IUPAC/Chemical Name:(3'R,4'S,5'R)-N-((3R,6S)-6-carbamoyltetrahydro-2H-pyran-3-yl)-6''-chloro-4'-(2-chloro-3-fluoropyridin-4-yl)-4,4-dimethyl-2''-oxodispiro[cyclohexane-1,2'-pyrrolidine-3',3''-indoline]-5'-carboxamide tosylate

InChi Key:NHIUKVHKLJSJEA-LINJWFRASA-N

InChi Code:InChI=1S/C30H34Cl2FN5O4.C7H8O3S/c1-28(2)8-10-29(11-9-28)30(18-5-3-15(31)13-19(18)37-27(30)41)21(17-7-12-35-24(32)22(17)33)23(38-29)26(40)36-16-4-6-20(25(34)39)42-14-16;1-6-2-4-7(5-3-6)11(8,9)10/h3,5,7,12-13,16,20-21,23,38H,4,6,8-11,14H2,1-2H3,(H2,34,39)(H,36,40)(H,37,41);2-5H,1H3,(H,8,9,10)/t16-,20+,21+,23-,30-;/m1./s1

SMILES Code:O=C([C@H](N1)[C@H](C2=C(F)C(Cl)=NC=C2)[C@]3(C(NC4=C3C=CC(Cl)=C4)=O)C51CCC(C)(C)CC5)N[C@H]6CO[C@H](C(N)=O)CC6.OS(=O)(C7=CC=C(C)C=C7)=O

Technical Data

Additional Information

 By preventing this MDM2-p53 interaction, the proteosome-mediated enzymatic degradation of p53 is inhibited and the transcriptional activity of p53 is restored. This results in the restoration of p53 signaling and leads to the p53-mediated induction of tumor cell apoptosis. MDM2, a zinc finger protein and a negative regulator of the p53 pathway, is overexpressed in cancer cells; it has been implicated in cancer cell proliferation and survival.   

References

1: Ishizawa J, Nakamaru K, Seki T, Tazaki K, Kojima K, Chachad D, Zhao R, Heese LE, Ma W, Ma MCJ, DiNardo CD, Pierce SA, Patel KP, Tse A, Davis RE, Rao A, Andreeff M. Predictive gene signatures determine tumor sensitivity to MDM2 inhibition. Cancer Res. 2018 Feb 28. pii: canres.0949.2017. doi: 10.1158/0008-5472.CAN-17-0949. [Epub ahead of print] PubMed PMID: 29490944.

2: Arnhold V, Schmelz K, Proba J, Winkler A, Wünschel J, Toedling J, Deubzer HE,Künkele A, Eggert A, Schulte JH, Hundsdoerfer P. Reactivating TP53 signaling by the novel MDM2 inhibitor DS-3032b as a therapeutic option for high-risk neuroblastoma. Oncotarget. 2017 Dec 18;9(2):2304-2319. doi: 10.18632/oncotarget.23409. eCollection 2018 Jan 5. PubMed PMID: 29416773; PubMed Central PMCID: PMC5788641.

3.Liao G, Yang D, Ma L, Li W, Hu L, Zeng L, Wu P, Duan L, Liu Z. The development of piperidinones as potent MDM2-P53 protein-protein interaction inhibitors for cancer therapy. Eur J Med Chem. 2018 Nov 5;159:1-9. doi: 10.1016/j.ejmech.2018.09.044. Epub 2018 Sep 18. Review. PubMed PMID: 30253242.