RO5045337 | RG7112 | R7112 | CAS#939981-39-2 | MDM2 antagonist

MedKoo Cat#: 202421 | Name: RO5045337

Description:

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

RO5045337, also known as RG7112, is a MDM2 antagonist with potential antineoplastic activity.

Chemical Structure

RO5045337

CAS#939981-39-2

Theoretical Analysis

MedKoo Cat#: 202421

Name: RO5045337

CAS#: 939981-39-2

Chemical Formula: C38H48Cl2N4O4S

Exact Mass: 726.2773

Molecular Weight: 726.28

Elemental Analysis: C, 62.71; H, 6.65; Cl, 9.74; N, 7.70; O, 8.79; S, 4.41

Price and Availability

Size	Price	Availability
5mg	USD 150.00	Ready to ship
10mg	USD 250.00	Ready to ship
25mg	USD 450.00	Ready to ship
50mg	USD 750.00	Ready to ship
100mg	USD 1,250.00	Ready to ship
200mg	USD 1,950.00	Ready to ship
500mg	USD 2,950.00	Ready to ship
1g	USD 4,650.00	2 Weeks
2g	USD 7,450.00	2 Weeks

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Related CAS #

No Data

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

Appearance

White to off-white 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, not in water

Shelf Life

>2 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

More Info

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#A7K11K15

QC Data

View QC data: current batch, Lot#A7K11K15

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

RO5045337 has an IC50 of 18 nM and a KD of 11 nM for binding to MDM2.

In vitro activity:

RO5045337 significantly reduced cellular viability of IMR5 (IC50, 562 nM) and LAN-5 (IC50, 430 nM), but not SK-N-BE(2) and SH-EP cells. RO5045337 restores p53 and p21 protein levels in IMR5 and LAN-5 in a dose-dependent manner. RO5045337 induces cell cycle arresting (60% G1 arresting) in WT-p53 cells (IMR5) Reference: Cancer Biother Radiopharm. 2019 May;34(4):252-257. https://pubmed.ncbi.nlm.nih.gov/30724592/

In vivo activity:

Oral administration of RO5045337 to human xenograft-bearing mice at nontoxic concentrations caused dose-dependent changes in proliferation/apoptosis biomarkers as well as tumor inhibition and regression. RO5045337 was highly synergistic with androgen deprivation in LNCaP xenograft tumors. Reference: Cancer Res. 2013 Apr 15;73(8):2587-97. https://pubmed.ncbi.nlm.nih.gov/23400593/

	Solvent	mg/mL	mM
Solubility
	DMF	25.0	34.40
	DMSO	12.5	17.20
	Ethanol	25.0	27.50

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 726.28 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Al-Ghabkari A, Narendran A. In Vitro Characterization of a Potent p53-MDM2 Inhibitor, RG7112 in Neuroblastoma Cancer Cell Lines. Cancer Biother Radiopharm. 2019 May;34(4):252-257. doi: 10.1089/cbr.2018.2732. Epub 2019 Feb 6. PMID: 30724592. 2. Iancu-Rubin C, Mosoyan G, Glenn K, Gordon RE, Nichols GL, Hoffman R. Activation of p53 by the MDM2 inhibitor RG7112 impairs thrombopoiesis. Exp Hematol. 2014 Feb;42(2):137-45.e5. doi: 10.1016/j.exphem.2013.11.012. Epub 2013 Dec 3. PMID: 24309210. 3. Tovar C, Graves B, Packman K, Filipovic Z, Higgins B, Xia M, Tardell C, Garrido R, Lee E, Kolinsky K, To KH, Linn M, Podlaski F, Wovkulich P, Vu B, Vassilev LT. MDM2 small-molecule antagonist RG7112 activates p53 signaling 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. PMID: 23400593. 4. Iancu-Rubin C, Mosoyan G, Glenn K, Gordon RE, Nichols GL, Hoffman R. Activation of p53 by the MDM2 inhibitor RG7112 impairs thrombopoiesis. Exp Hematol. 2014 Feb;42(2):137-45.e5. doi: 10.1016/j.exphem.2013.11.012. Epub 2013 Dec 3. PMID: 24309210.

In vitro protocol:

In vivo protocol:

1. Tovar C, Graves B, Packman K, Filipovic Z, Higgins B, Xia M, Tardell C, Garrido R, Lee E, Kolinsky K, To KH, Linn M, Podlaski F, Wovkulich P, Vu B, Vassilev LT. MDM2 small-molecule antagonist RG7112 activates p53 signaling 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. PMID: 23400593. 2. Iancu-Rubin C, Mosoyan G, Glenn K, Gordon RE, Nichols GL, Hoffman R. Activation of p53 by the MDM2 inhibitor RG7112 impairs thrombopoiesis. Exp Hematol. 2014 Feb;42(2):137-45.e5. doi: 10.1016/j.exphem.2013.11.012. Epub 2013 Dec 3. PMID: 24309210.

1: Ding Q, Zhang Z, Liu JJ, Jiang N, Zhang J, Ross TM, Chu XJ, Bartkovitz D, Podlaski F, Janson C, Tovar C, Filipovic ZM, Higgins B, Glenn K, Packman K, Vassilev LT, Graves B. Discovery of RG7388, a Potent and Selective p53-MDM2 Inhibitor in Clinical Development. 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, Tardell C, Garrido R, Lee E, Kolinsky K, To KH, Linn M, Podlaski F, Wovkulich P, Vu B, Vassilev LT. MDM2 small-molecule antagonist RG7112 activates p53 signaling 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, Heil F, Rueger R, Graves B, Ding M, Geho D, Middleton SA, Vassilev LT, Nichols GL, Bui BN. Effect of the MDM2 antagonist RG7112 on the P53 pathway in patients with MDM2-amplified, well-differentiated or dedifferentiated 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 Pediatric Preclinical Testing Program. Pediatr Blood Cancer. 2013 Apr;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-molecule inhibitors of p53-MDM2 interaction: the 2006-2010 update. Curr Pharm Des. 2011;17(6):536-59. Review. PubMed PMID: 21391905.