Ro 48-8071 fumarate
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MedKoo CAT#: 510318

CAS#: 189197-69-1(fumarate)

Description: Ro 48-8071 is an orally active cholesterol synthesis inhibitor or a 2,3-oxidosqualene:lanosterol cyclase (OSC) inhibitor. OSC (EC 5.4.99.7) represents a unique target for a cholesterol-lowering drug. Partial inhibition of OSC should reduce synthesis of lanosterol and subsequent sterols, and also stimulate the production of epoxysterols that repress HMG-CoA reductase expression, generating a synergistic, self-limited negative regulatory loop.


Chemical Structure

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Ro 48-8071 fumarate
CAS# 189197-69-1(fumarate)

Theoretical Analysis

MedKoo Cat#: 510318
Name: Ro 48-8071 fumarate
CAS#: 189197-69-1(fumarate)
Chemical Formula: C27H31BrFNO6
Exact Mass:
Molecular Weight: 564.45
Elemental Analysis: C, 57.45; H, 5.54; Br, 14.16; F, 3.37; N, 2.48; O, 17.01

Price and Availability

Size Price Availability Quantity
25.0mg USD 90.0 Ready to ship
50.0mg USD 150.0 Ready to ship
100.0mg USD 250.0 Ready to ship
200.0mg USD 450.0 Ready to ship
500.0mg USD 950.0 Ready to ship
1.0g USD 1750.0 Ready to ship
2.0g USD 3250.0 Ready to ship
5.0g USD 5850.0 2 Weeks
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Related CAS #: 189197-69-1(fumarate)   161582-11-2 (free base)    

Synonym: Ro 488071; Ro488071; Ro-488071; Ro 488071; Ro-488071; Ro488071; Ro 48-8071 fumarate;

IUPAC/Chemical Name: (4-((6-(allyl(methyl)amino)hexyl)oxy)-2-fluorophenyl)(4-bromophenyl)methanone fumarate

InChi Key: XCYAYLWZCRGKDS-WLHGVMLRSA-N

InChi Code: InChI=1S/C23H27BrFNO2.C4H4O4/c1-3-14-26(2)15-6-4-5-7-16-28-20-12-13-21(22(25)17-20)23(27)18-8-10-19(24)11-9-18;5-3(6)1-2-4(7)8/h3,8-13,17H,1,4-7,14-16H2,2H3;1-2H,(H,5,6)(H,7,8)/b;2-1+

SMILES Code: O=C(C1=CC=C(OCCCCCCN(CC=C)C)C=C1F)C2=CC=C(Br)C=C2.O=C(O)/C=C/C(O)=O

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

Biological target: Ro 48-8071 fumarate is an inhibitor of OSC (Oxidosqualene cyclase) with IC50 of appr 6.5 nM.
In vitro activity: Addition of Ro48‐8071 to self‐renewing T2EC cells caused reduction in cell number, detectable at the beginning of treatment and becoming significant by fourth day after inhibitor addition, when treated populations showed reduction in cell number in the order of 40% compared to untreated control (Fig. 1: 1.0×106 ± 0.2 and 1.7×106 ± 0.4, respectively). This effect was amplified over time and after 7 days treatment, cell number of Ro48‐8071‐treated population was four times lower than that of the control group (Fig. 1: 8.6 ×106 ± 1.4 and 3.2×107 ± 0.3 respectively). Reference: Cell Prolif. 2011 Oct; 44(5): 441–452. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6495882/
In vivo activity: Treatment with Ro 48‐8071 resulted in a statistically significant decrease in axin2 expression (Figure 1b). However, treatment with lonafarnib, which inhibits farnesylated isoprenoids did not result in a statistically significant decrease in axin2 expression. This study next analyzed the effects of increased concentrations of Ro 48‐8071 on axin2 expression. Embryos were treated with 1, 2, or 3 μM Ro 48‐8071 and the level of axin2 expression was measured by qPCR at 30 HPF. This study observed decreased axin2 expression in all groups, with the most dramatic decrease in embryos treated with the highest concentration of 3 μM (Figure 1c). Reference: Genesis. 2020 Dec; 58(12): e23397. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7816230/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 56.0 99.2
Ethanol 11.0 19.5

Preparing Stock Solutions

The following data is based on the product molecular weight 564.45 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.

Recalculate based on batch purity %
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. Liang Y, Goyette S, Hyder SM. Cholesterol biosynthesis inhibitor RO 48-8071 reduces progesterone receptor expression and inhibits progestin-dependent stem cell-like cell growth in hormone-dependent human breast cancer cells. Breast Cancer (Dove Med Press). 2017 Jul 7;9:487-494. doi: 10.2147/BCTT.S140265. PMID: 28744156; PMCID: PMC5511027. 2. Mejia-Pous C, Damiola F, Gandrillon O. Cholesterol synthesis-related enzyme oxidosqualene cyclase is required to maintain self-renewal in primary erythroid progenitors. Cell Prolif. 2011 Oct;44(5):441-52. doi: 10.1111/j.1365-2184.2011.00771.x. PMID: 21951287; PMCID: PMC6495882. 3. Castro VL, Reyes-Nava NG, Sanchez BB, Gonzalez CG, Paz D, Quintana AM. Activation of WNT signaling restores the facial deficits in a zebrafish with defects in cholesterol metabolism. Genesis. 2020 Dec;58(12):e23397. doi: 10.1002/dvg.23397. Epub 2020 Nov 16. PMID: 33197123; PMCID: PMC7816230. 4. Maione F, Oliaro-Bosso S, Meda C, Di Nicolantonio F, Bussolino F, Balliano G, Viola F, Giraudo E. The cholesterol biosynthesis enzyme oxidosqualene cyclase is a new target to impair tumour angiogenesis and metastasis dissemination. Sci Rep. 2015 Mar 12;5:9054. doi: 10.1038/srep09054. PMID: 25761781; PMCID: PMC4357009.
In vitro protocol: 1. Liang Y, Goyette S, Hyder SM. Cholesterol biosynthesis inhibitor RO 48-8071 reduces progesterone receptor expression and inhibits progestin-dependent stem cell-like cell growth in hormone-dependent human breast cancer cells. Breast Cancer (Dove Med Press). 2017 Jul 7;9:487-494. doi: 10.2147/BCTT.S140265. PMID: 28744156; PMCID: PMC5511027. 2. Mejia-Pous C, Damiola F, Gandrillon O. Cholesterol synthesis-related enzyme oxidosqualene cyclase is required to maintain self-renewal in primary erythroid progenitors. Cell Prolif. 2011 Oct;44(5):441-52. doi: 10.1111/j.1365-2184.2011.00771.x. PMID: 21951287; PMCID: PMC6495882.
In vivo protocol: 1. Castro VL, Reyes-Nava NG, Sanchez BB, Gonzalez CG, Paz D, Quintana AM. Activation of WNT signaling restores the facial deficits in a zebrafish with defects in cholesterol metabolism. Genesis. 2020 Dec;58(12):e23397. doi: 10.1002/dvg.23397. Epub 2020 Nov 16. PMID: 33197123; PMCID: PMC7816230. 2. Maione F, Oliaro-Bosso S, Meda C, Di Nicolantonio F, Bussolino F, Balliano G, Viola F, Giraudo E. The cholesterol biosynthesis enzyme oxidosqualene cyclase is a new target to impair tumour angiogenesis and metastasis dissemination. Sci Rep. 2015 Mar 12;5:9054. doi: 10.1038/srep09054. PMID: 25761781; PMCID: PMC4357009.

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1: Mafuvadze B, Liang Y, Hyder SM. Cholesterol synthesis inhibitor RO 48-8071 suppresses transcriptional activity of human estrogen and androgen receptor. Oncol Rep. 2014 Oct;32(4):1727-33. doi: 10.3892/or.2014.3332. Epub 2014 Jul 15. PubMed PMID: 25051231.

2: Liang Y, Besch-Williford C, Aebi JD, Mafuvadze B, Cook MT, Zou X, Hyder SM. Cholesterol biosynthesis inhibitors as potent novel anti-cancer agents: suppression of hormone-dependent breast cancer by the oxidosqualene cyclase inhibitor RO 48-8071. Breast Cancer Res Treat. 2014 Jul;146(1):51-62. doi: 10.1007/s10549-014-2996-5. Epub 2014 May 31. PubMed PMID: 24878988.

3: Chuang JC, Valasek MA, Lopez AM, Posey KS, Repa JJ, Turley SD. Sustained and selective suppression of intestinal cholesterol synthesis by Ro 48-8071, an inhibitor of 2,3-oxidosqualene:lanosterol cyclase, in the BALB/c mouse. Biochem Pharmacol. 2014 Apr 1;88(3):351-63. doi: 10.1016/j.bcp.2014.01.031. Epub 2014 Jan 31. PubMed PMID: 24486573; PubMed Central PMCID: PMC3989900.

4: Peffley DM, Gayen AK, Morand OH. Down-regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase mRNA levels and synthesis in syrian hamster C100 cells by the oxidosqualene cyclase inhibitor [4'-(6-allyl-ethyl-amino-hexyloxy)-2'-fluoro-phenyl]-(4-bromophenyl)-me thanone (Ro 48-8071): comparison to simvastatin. Biochem Pharmacol. 1998 Aug 15;56(4):439-49. PubMed PMID: 9763219.



Additional Information

Related CAS#
CAS#189197-69-1(Ro 48-8071 fumarate salt);
CAS#161582-11-2 (Ro 48-8071 free base)