RA-9
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MedKoo CAT#: 408099

CAS#: 919091-63-7

Description: RA-9 is a potent and selective proteasome-associated deubiquitinating enzymes (DUBs) inhibitor with favorable toxicity profile and anticancer activity.


Chemical Structure

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RA-9
CAS# 919091-63-7

Theoretical Analysis

MedKoo Cat#: 408099
Name: RA-9
CAS#: 919091-63-7
Chemical Formula: C19H15N3O5
Exact Mass: 365.10
Molecular Weight: 365.350
Elemental Analysis: C, 62.46; H, 4.14; N, 11.50; O, 21.90

Price and Availability

Size Price Availability Quantity
50mg USD 450 2 Weeks
100mg USD 750 2 Weeks
200mg USD 1250 2 Weeks
500mg USD 2650 2 Weeks
1g USD 3650 2 Weeks
2g USD 5950 2 Weeks
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Synonym: RA-9; RA 9; RA9; RA-9 UPS inhibitor

IUPAC/Chemical Name: (3E,5E)-3,5-Bis[(4-nitrophenyl)methylene]-4-piperidinone

InChi Key: YUYPWAMLWZVHAE-KAVGSWPWSA-N

InChi Code: InChI=1S/C19H15N3O5/c23-19-15(9-13-1-5-17(6-2-13)21(24)25)11-20-12-16(19)10-14-3-7-18(8-4-14)22(26)27/h1-10,20H,11-12H2/b15-9+,16-10+

SMILES Code: O=C1/C(CNC/C1=C\C2=CC=C([N+]([O-])=O)C=C2)=C/C3=CC=C([N+]([O-])=O)C=C3

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

More Info: Ovarian cancer is the deadliest of the gynecologic malignancies. Carcinogenic progression is accompanied by upregulation of ubiquitin-dependent protein degradation machinery as a mechanism to compensate with elevated endogenous proteotoxic stress. Recent studies support the notion that deubiquitinating enzymes (DUB) are essential factors in proteolytic degradation and that their aberrant activity is linked to cancer progression and chemoresistance. Thus, DUBs are an attractive therapeutic target for ovarian cancer.

Product Data:
Biological target: RA-9 blocks ubiquitin-dependent protein degradation without impacting 20S proteasome proteolytic activity. RA-9 selectively induces onset of apoptosis in ovarian cancer cell lines and primary cultures derived from donors. RA-9 induces endoplasmic reticulum (ER)-stress responses in ovarian cancer cells.
In vitro activity: RA‑9 exerted an inhibitory effect on the adhesion and proliferation of H2373 cells, whereas it had no effect on A549 cells. In H2373 cells, treatment with RA‑9 decreased its phosphorylation compared to the DMSO control. Reference: Int J Oncol. 2020 Jul;57(1):80-86. https://pubmed.ncbi.nlm.nih.gov/32236606/
In vivo activity: This study demonstrated that RA-9 is efficient in exerting cytotoxic effects and inhibitory actions on cell proliferation and hormone secretion by modulating the expression of pERK1/2, pCREB and p27. Inhibition of USP8 might be a strategy to target both USP8-WT and USP8-mutated tumors in CD patients. Reference: Endocr Relat Cancer. 2021 Jun 28;28(8):573-582. https://pubmed.ncbi.nlm.nih.gov/34086599/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 4.2 11.41

Preparing Stock Solutions

The following data is based on the product molecular weight 365.35 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. Mirzapoiazova T, Pozhitkov A, Nam A, Mambetsariev I, Nelson MS, Tan YC, Zhang K, Raz D, Singhal S, Nasser MW, Kulkarni P, Batra SK, Sattler M, Salgia R. Effects of selected deubiquitinating enzyme inhibitors on the proliferation and motility of lung cancer and mesothelioma cell lines. Int J Oncol. 2020 Jul;57(1):80-86. doi: 10.3892/ijo.2020.5034. Epub 2020 Apr 1. PMID: 32236606; PMCID: PMC7252467. 2. Vogel RI, Coughlin K, Scotti A, Iizuka Y, Anchoori R, Roden RB, Marastoni M, Bazzaro M. Simultaneous inhibition of deubiquitinating enzymes (DUBs) and autophagy synergistically kills breast cancer cells. Oncotarget. 2015 Feb 28;6(6):4159-70. doi: 10.18632/oncotarget.2904. PMID: 25784654; PMCID: PMC4414179. 3. Winkel AF, Engel CK, Margerie D, Kannt A, Szillat H, Glombik H, Kallus C, Ruf S, Güssregen S, Riedel J, Herling AW, von Knethen A, Weigert A, Brüne B, Schmoll D. Characterization of RA839, a Noncovalent Small Molecule Binder to Keap1 and Selective Activator of Nrf2 Signaling. J Biol Chem. 2015 Nov 20;290(47):28446-28455. doi: 10.1074/jbc.M115.678136. Epub 2015 Oct 12. PMID: 26459563; PMCID: PMC4653701. 4. Coughlin K, Anchoori R, Iizuka Y, Meints J, MacNeill L, Vogel RI, Orlowski RZ, Lee MK, Roden RB, Bazzaro M. Small-molecule RA-9 inhibits proteasome-associated DUBs and ovarian cancer in vitro and in vivo via exacerbating unfolded protein responses. Clin Cancer Res. 2014 Jun 15;20(12):3174-86. doi: 10.1158/1078-0432.CCR-13-2658. Epub 2014 Apr 11. PMID: 24727327; PMCID: PMC4269153.
In vitro protocol: 1. Mirzapoiazova T, Pozhitkov A, Nam A, Mambetsariev I, Nelson MS, Tan YC, Zhang K, Raz D, Singhal S, Nasser MW, Kulkarni P, Batra SK, Sattler M, Salgia R. Effects of selected deubiquitinating enzyme inhibitors on the proliferation and motility of lung cancer and mesothelioma cell lines. Int J Oncol. 2020 Jul;57(1):80-86. doi: 10.3892/ijo.2020.5034. Epub 2020 Apr 1. PMID: 32236606; PMCID: PMC7252467. 2. Vogel RI, Coughlin K, Scotti A, Iizuka Y, Anchoori R, Roden RB, Marastoni M, Bazzaro M. Simultaneous inhibition of deubiquitinating enzymes (DUBs) and autophagy synergistically kills breast cancer cells. Oncotarget. 2015 Feb 28;6(6):4159-70. doi: 10.18632/oncotarget.2904. PMID: 25784654; PMCID: PMC4414179.
In vivo protocol: 1. Winkel AF, Engel CK, Margerie D, Kannt A, Szillat H, Glombik H, Kallus C, Ruf S, Güssregen S, Riedel J, Herling AW, von Knethen A, Weigert A, Brüne B, Schmoll D. Characterization of RA839, a Noncovalent Small Molecule Binder to Keap1 and Selective Activator of Nrf2 Signaling. J Biol Chem. 2015 Nov 20;290(47):28446-28455. doi: 10.1074/jbc.M115.678136. Epub 2015 Oct 12. PMID: 26459563; PMCID: PMC4653701. 2. Coughlin K, Anchoori R, Iizuka Y, Meints J, MacNeill L, Vogel RI, Orlowski RZ, Lee MK, Roden RB, Bazzaro M. Small-molecule RA-9 inhibits proteasome-associated DUBs and ovarian cancer in vitro and in vivo via exacerbating unfolded protein responses. Clin Cancer Res. 2014 Jun 15;20(12):3174-86. doi: 10.1158/1078-0432.CCR-13-2658. Epub 2014 Apr 11. PMID: 24727327; PMCID: PMC4269153.

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1. Coughlin K, Anchoori R, Iizuka Y, et al. Small-molecule RA-9 inhibits proteasome-associated DUBs and ovarian cancer in vitro and in vivo via exacerbating unfolded protein responses. Clin Cancer Res. 2014;20(12):3174‐3186. doi:10.1158/1078-0432.CCR-13-2658