RX-3117 | TV-1360 | CAS#865838-26-2 | DNA synthesis inhibitor

MedKoo Cat#: 206092 | Name: RX-3117

Description:

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

RX-3117, also known as TV-1360 and fluorocyclopentenylcytosine, is an orally available and potent DNA synthesis inhibitor with potential antineoplastic activity. Upon administration, the cytidine analogue RX-3117 is taken up by cells through a carrier-mediated transporter, phosphorylated by uridine cytidine kinase (UCK) and then further phosphorylated to its diphosphate (RX-DP) and triphosphate forms (RX-TP). The triphosphate form is incorporated into RNA and inhibits RNA synthesis. The diphosphate RX-DP is reduced by ribonucleotide reductase (RR) to dRX-DP; its triphosphate form (dRX-TP) is incorporated into DNA. In addition, RX-3117 also inhibits DNA methyltransferase 1 (DNMT1).

Chemical Structure

RX-3117

CAS#865838-26-2

Theoretical Analysis

MedKoo Cat#: 206092

Name: RX-3117

CAS#: 865838-26-2

Chemical Formula: C10H12FN3O4

Exact Mass: 257.0812

Molecular Weight: 257.22

Elemental Analysis: C, 46.69; H, 4.70; F, 7.39; N, 16.34; O, 24.88

Price and Availability

Size	Price	Availability
50mg	USD 950.00	2 Weeks
100mg	USD 1,750.00	2 Weeks
200mg	USD 2,450.00	2 Weeks
500mg	USD 3,650.00	2 Weeks
1g	USD 4,850.00	2 Weeks
2g	USD 7,850.00	2 Weeks

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Synonym

RX3117; RX3117; RX 3117; TV1360; TV1360; TV 1360; fluorocyclopentenylcytosine

IUPAC/Chemical Name

4-(4-(4-fluorophenyl)-1-(3-phenylpropyl)-5-(pyridin-4-yl)-1H-imidazol-2-yl)but-3-yn-1-ol

InChi Key

QSUSKMBNZQHHPA-UHFFFAOYSA-N

InChi Code

InChI=1S/C27H24FN3O/c28-24-13-11-22(12-14-24)26-27(23-15-17-29-18-16-23)31(25(30-26)10-4-5-20-32)19-6-9-21-7-2-1-3-8-21/h1-3,7-8,11-18,32H,5-6,9,19-20H2

SMILES Code

OCCC#CC1=NC(C2=CC=C(F)C=C2)=C(C3=CC=NC=C3)N1CCCC4=CC=CC=C4

Appearance

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

To be determined

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

Instruction

View handling instruction

Biological target:

RX-3117 inhibits DNA methyltransferase 1 (DNMT1). RX-3117 shows antiproliferative and anti-tumor activity. RX-3117 induces cell cycle arrest at S phase and apoptosis.

In vitro activity:

This study identified which of the form of uridine-cytidine kinase (UCK), UCK1 or UCK2, is responsible for RX-3117 phosphorylation. Transfection of UCK2-siRNA effectively downregulated UCK2 expression and protected cells against RX-3117, indicating that UCK2 plays a crucial role in RX-3117 activation. RX-3117 is primarily activated by UCK2, offering a potential method for identifying patients who might benefit from RX-3117 treatment in clincal studies. Reference: PLoS One. 2016 Sep 9;11(9):e0162901. https://pubmed.ncbi.nlm.nih.gov/27612203/

In vivo activity:

RX-3117 displayed promising anticancer activity in multiple human tumor xenograft models in mice, including gemcitabine-resistant tumors. RX-3117 outperformed gemcitabine in specific models, highlighting its potential as an effective alternative for cancer treatment, particularly in cases of gemcitabine resistance. Reference: Anticancer Res. 2014 Dec;34(12):6951-9. https://pubmed.ncbi.nlm.nih.gov/25503121/

Preparing Stock Solutions

The following data is based on the product molecular weight 257.22 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. Sarkisjan D, Julsing JR, El Hassouni B, Honeywell RJ, Kathmann I, Matherly LH, Lee YB, Kim DJ, Peters GJ. RX-3117 (Fluorocyclopentenyl-Cytosine)-Mediated Down-Regulation of DNA Methyltransferase 1 Leads to Protein Expression of Tumor-Suppressor Genes and Increased Functionality of the Proton-Coupled Folate Carrier. Int J Mol Sci. 2020 Apr 14;21(8):2717. doi: 10.3390/ijms21082717. PMID: 32295203; PMCID: PMC7215832. 2. Sarkisjan D, Julsing JR, Smid K, de Klerk D, van Kuilenburg AB, Meinsma R, Lee YB, Kim DJ, Peters GJ. The Cytidine Analog Fluorocyclopentenylcytosine (RX-3117) Is Activated by Uridine-Cytidine Kinase 2. PLoS One. 2016 Sep 9;11(9):e0162901. doi: 10.1371/journal.pone.0162901. PMID: 27612203; PMCID: PMC5017758. 3. Babiker H, Schlegel PJ, Hicks LG, Bullock AJ, Burhani N, Mahadevan D, Elquza E, Borad MJ, Benaim E, Peterson C, Heaton C, Ocean AJ. A multicenter phase 1/2 study investigating the safety, pharmacokinetics, pharmacodynamics and efficacy of a small molecule antimetabolite, RX-3117, plus nab-paclitaxel in pancreatic adenocarcinoma. Invest New Drugs. 2022 Feb;40(1):81-90. doi: 10.1007/s10637-021-01164-9. Epub 2021 Aug 21. PMID: 34417914. 4. Yang MY, Lee YB, Ahn CH, Kaye J, Fine T, Kashi R, Ohne O, Smid K, Peters GJ, Kim DJ. A novel cytidine analog, RX-3117, shows potent efficacy in xenograft models, even in tumors that are resistant to gemcitabine. Anticancer Res. 2014 Dec;34(12):6951-9. PMID: 25503121.

In vitro protocol:

In vivo protocol:

1. Babiker H, Schlegel PJ, Hicks LG, Bullock AJ, Burhani N, Mahadevan D, Elquza E, Borad MJ, Benaim E, Peterson C, Heaton C, Ocean AJ. A multicenter phase 1/2 study investigating the safety, pharmacokinetics, pharmacodynamics and efficacy of a small molecule antimetabolite, RX-3117, plus nab-paclitaxel in pancreatic adenocarcinoma. Invest New Drugs. 2022 Feb;40(1):81-90. doi: 10.1007/s10637-021-01164-9. Epub 2021 Aug 21. PMID: 34417914. 2. Yang MY, Lee YB, Ahn CH, Kaye J, Fine T, Kashi R, Ohne O, Smid K, Peters GJ, Kim DJ. A novel cytidine analog, RX-3117, shows potent efficacy in xenograft models, even in tumors that are resistant to gemcitabine. Anticancer Res. 2014 Dec;34(12):6951-9. PMID: 25503121.

1: Balboni B, El Hassouni B, Honeywell RJ, Sarkisjan D, Giovannetti E, Poore J, Heaton C, Peterson C, Benaim E, Lee YB, Kim DJ, Peters GJ. RX-3117 (fluorocyclopentenyl cytosine): a novel specific antimetabolite for selective cancer treatment. Expert Opin Investig Drugs. 2019 Apr;28(4):311-322. doi: 10.1080/13543784.2019.1583742. Epub 2019 Mar 16. PMID: 30879349. 2: Sarkisjan D, Julsing JR, El Hassouni B, Honeywell RJ, Kathmann I, Matherly LH, Lee YB, Kim DJ, Peters GJ. RX-3117 (Fluorocyclopentenyl-Cytosine)-Mediated Down-Regulation of DNA Methyltransferase 1 Leads to Protein Expression of Tumor- Suppressor Genes and Increased Functionality of the Proton-Coupled Folate Carrier. Int J Mol Sci. 2020 Apr 14;21(8):2717. doi: 10.3390/ijms21082717. PMID: 32295203; PMCID: PMC7215832. 3: Sarkisjan D, Julsing JR, Smid K, de Klerk D, van Kuilenburg AB, Meinsma R, Lee YB, Kim DJ, Peters GJ. The Cytidine Analog Fluorocyclopentenylcytosine (RX-3117) Is Activated by Uridine-Cytidine Kinase 2. PLoS One. 2016 Sep 9;11(9):e0162901. doi: 10.1371/journal.pone.0162901. PMID: 27612203; PMCID: PMC5017758. 4: Peters GJ, Smid K, Vecchi L, Kathmann I, Sarkisjan D, Honeywell RJ, Losekoot N, Ohne O, Orbach A, Blaugrund E, Jeong LS, Lee YB, Ahn CH, Kim DJ. Metabolism, mechanism of action and sensitivity profile of fluorocyclopentenylcytosine (RX-3117; TV-1360). Invest New Drugs. 2013 Dec;31(6):1444-57. doi: 10.1007/s10637-013-0025-x. Epub 2013 Sep 19. PMID: 24048768. 5: Babiker H, Schlegel PJ, Hicks LG, Bullock AJ, Burhani N, Mahadevan D, Elquza E, Borad MJ, Benaim E, Peterson C, Heaton C, Ocean AJ. A multicenter phase 1/2 study investigating the safety, pharmacokinetics, pharmacodynamics and efficacy of a small molecule antimetabolite, RX-3117, plus nab-paclitaxel in pancreatic adenocarcinoma. Invest New Drugs. 2022 Feb;40(1):81-90. doi: 10.1007/s10637-021-01164-9. Epub 2021 Aug 21. PMID: 34417914. 6: El Hassouni B, Infante J, Mantini G, Ricci C, Funel N, Giovannetti E, Peters GJ. Uridine Cytidine Kinase 2 as a Potential Biomarker for Treatment with RX-3117 in Pancreatic Cancer. Anticancer Res. 2019 Jul;39(7):3609-3614. doi: 10.21873/anticanres.13508. PMID: 31262886. 7: Yang MY, Lee YB, Ahn CH, Kaye J, Fine T, Kashi R, Ohne O, Smid K, Peters GJ, Kim DJ. A novel cytidine analog, RX-3117, shows potent efficacy in xenograft models, even in tumors that are resistant to gemcitabine. Anticancer Res. 2014 Dec;34(12):6951-9. PMID: 25503121. 8: Sarkisjan D, van den Berg J, Smit E, Lee YB, Kim DJ, Peters GJ. The radiosensitizing effect of fluorocyclopentenyl-cytosine (RX-3117) in ovarian and lung cancer cell lines. Nucleosides Nucleotides Nucleic Acids. 2016 Dec;35(10-12):619-630. doi: 10.1080/15257770.2016.1216565. PMID: 27906620. 9: Honeywell RJ, Sarkisjan D, Kathmann I, Kristensen MH, Peters GJ. Sensitive liquid chromatography mass spectrometry (LC-MS) assay reveals novel insights on DNA methylation and incorporation of gemcitabine, its metabolite difluorodeoxyuridine, deoxyuridine, and RX-3117 into DNA. Nucleosides Nucleotides Nucleic Acids. 2016 Dec;35(10-12):652-662. doi: 10.1080/15257770.2016.1216566. PMID: 27906622. 10: Peters GJ. Novel developments in the use of antimetabolites. Nucleosides Nucleotides Nucleic Acids. 2014;33(4-6):358-74. doi: 10.1080/15257770.2014.894197. PMID: 24940694. 11: Fu Y, Wei XD, Guo L, Wu K, Le J, Ma Y, Kong X, Tong Y, Wu H. The Metabolic and Non-Metabolic Roles of UCK2 in Tumor Progression. Front Oncol. 2022 May 20;12:904887. doi: 10.3389/fonc.2022.904887. PMID: 35669416; PMCID: PMC9163393. 12: Honeywell RJ, Sarkisjan D, Kristensen MH, de Klerk DJ, Peters GJ. DNA methyltransferases expression in normal tissues and various human cancer cell lines, xenografts and tumors. Nucleosides Nucleotides Nucleic Acids. 2018;37(12):696-708. doi: 10.1080/15257770.2018.1498516. Epub 2019 Jan 19. PMID: 30663502. 13: Mutlu O, Ugurel OM, Sariyer E, Ata O, Inci TG, Ugurel E, Kocer S, Turgut- Balik D. Targeting SARS-CoV-2 Nsp12/Nsp8 interaction interface with approved and investigational drugs: an in silico structure-based approach. J Biomol Struct Dyn. 2022 Feb;40(2):918-930. doi: 10.1080/07391102.2020.1819882. Epub 2020 Sep 16. PMID: 32933378; PMCID: PMC7544933. 14: Lian Y, Huang Z, Liu X, Deng Z, Gao D, Wang X. Discovery of Ten Anti-HIV Hit Compounds and Preliminary Pharmacological Mechanisms Studies. Curr HIV Res. 2024;22(2):82-90. doi: 10.2174/011570162X301289240320082840. PMID: 38532605.