RO5045337

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

Description:RO5045337, also known as RG7112, is a MDM2 antagonist with potential antineoplastic activity. RO5045337 binds to MDM2, thereby preventing the binding of the 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, which may result in the restoration of p53 signaling and thus the p53-mediated induction of tumor cell apoptosis. MDM2, a zinc finger protein, is a negative regulator of the p53 pathway; often overexpressed in cancer cells, it has been implicated in cancer cell proliferation and survival.

Price and Availability

RO5045337, purity > 98%, is in stock. Current shipping out time is about 2 weeks after order is received. CoA, QC data and MSDS documents are available in one week after order is received.

Chemical Structure

Theoretical Analysis

MedKoo Cat#: 202421Name: RO5045337CAS#: 939981-39-2Chemical Formula: C38H48Cl2N4O4SExact Mass: 726.27733Molecular Weight: 727.78Elemental Analysis: C, 62.71; H, 6.65; Cl, 9.74; N, 7.70; O, 8.79; S, 4.41

Synonym:R7112 RG7112 RG 7112; RG7112; RO5045337; RO 5045337; RO5045337

IUPAC/Chemical Name:((4S,5R)-2-(4-(tert-butyl)-2-ethoxyphenyl)-4,5-bis(4-chlorophenyl)-4,5-dimethyl-4,5-dihydro-1H-imidazol-1-yl)(4-(3-(methylsulfonyl)propyl)piperazin-1-yl)methanone

InChi Key:QBGKPEROWUKSBK-QPPIDDCLSA-N

InChi Code:InChI=1S/C38H48Cl2N4O4S/c1-8-48-33-26-29(36(2,3)4)14-19-32(33)34-41-37(5,27-10-15-30(39)16-11-27)38(6,28-12-17-31(40)18-13-28)44(34)35(45)43-23-21-42(22-24-43)20-9-25-49(7,46)47/h10-19,26H,8-9,20-25H2,1-7H3/t37-,38+/m0/s1

SMILES Code:O=C(N1[C@](C)(C2=CC=C(Cl)C=C2)[C@](C)(C3=CC=C(Cl)C=C3)N=C1C4=CC=C(C(C)(C)C)C=C4OCC)N5CCN(CCCS(=O)(C)=O)CC5

Technical Data

Additional Information

References

1: Ding Q, Zhang Z, Liu JJ, Jiang N, Zhang J, RossTM, Chu XJ, Bartkovitz D, Podlaski F, Janson C, Tovar C, Filipovic ZM,Higgins B, Glenn K, Packman K, Vassilev LT, Graves B. Discovery ofRG7388, a Potent and Selective p53-MDM2 Inhibitor in ClinicalDevelopment. J Med Chem. 2013 Jul 16. [Epub ahead of print] PubMed PMID:23808545.

2: Tovar C, Graves B, Packman K, Filipovic Z, Higgins B, Xia M, TardellC, Garrido R, Lee E, Kolinsky K, To KH, Linn M, Podlaski F, Wovkulich P,Vu B, Vassilev LT. MDM2 small-molecule antagonist RG7112 activates p53signaling and regresses human tumors in preclinical cancer models.Cancer Res. 2013 Apr 15;73(8):2587-97. doi:10.1158/0008-5472.CAN-12-2807. Epub 2013 Feb 11. PubMed PMID: 23400593.

3: Ray-Coquard I, Blay JY, Italiano A, Le Cesne A, Penel N, Zhi J, HeilF, Rueger R, Graves B, Ding M, Geho D, Middleton SA, Vassilev LT,Nichols GL, Bui BN. Effect of the MDM2 antagonist RG7112 on the P53pathway in patients with MDM2-amplified, well-differentiated ordedifferentiated liposarcoma: an exploratory proof-of-mechanism study.Lancet Oncol. 2012 Nov;13(11):1133-40. doi:10.1016/S1470-2045(12)70474-6. Epub 2012 Oct 17. PubMed PMID: 23084521.

4: Carol H, Reynolds CP, Kang MH, Keir ST, Maris JM, Gorlick R, Kolb EA,Billups CA, Geier B, Kurmasheva RT, Houghton PJ, Smith MA, Lock RB.Initial testing of the MDM2 inhibitor RG7112 by the PediatricPreclinical Testing Program. Pediatr Blood Cancer. 2013Apr;60(4):633-41. doi: 10.1002/pbc.24235. Epub 2012 Jul 2. PubMed PMID:22753001; PubMed Central PMCID: PMC3495996.

5: Millard M, Pathania D, Grande F, Xu S, Neamati N. Small-moleculeinhibitors of p53-MDM2 interaction: the 2006-2010 update. Curr PharmDes. 2011;17(6):536-59. Review. PubMed PMID: 21391905.