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MedKoo Cat#: 202331 | Name: PR-104
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Description:

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

PR-104 is a non-toxic nitrogen mustard pre-prodrug with potential antitumor activity. Upon intravenous administration, PR-104 is converted by systemic phosphatases to the alcohol intermediate PR-104A, which is reduced to form hydroxylamine PR-104H under hypoxic conditions. PR-104H specifically crosslinks hypoxic tumor cell DNA, resulting in the inhibition of DNA repair and synthesis, cell-cycle arrest, and apoptosis in susceptible hypoxic tumor cell populations while sparing normoxic tissues.

Chemical Structure

PR-104
PR-104
CAS#851627-62-8

Theoretical Analysis

MedKoo Cat#: 202331

Name: PR-104

CAS#: 851627-62-8

Chemical Formula: C14H20BrN4O12PS

Exact Mass: 577.9719

Molecular Weight: 579.27

Elemental Analysis: C, 29.03; H, 3.48; Br, 13.79; N, 9.67; O, 33.14; P, 5.35; S, 5.54

Price and Availability

Size Price Availability Quantity
5mg USD 750.00 2 Weeks
10mg USD 1,350.00 2 Weeks
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Related CAS #
No Data
Synonym
PR 104; PR-104; PR104.
IUPAC/Chemical Name
2-((2-bromoethyl)(2,4-dinitro-6-((2-(phosphonooxy)ethyl)carbamoyl)phenyl)amino)ethyl methanesulfonate
InChi Key
GZSOKPMDWVRVMG-UHFFFAOYSA-N
InChi Code
InChI=1S/C14H20BrN4O12PS/c1-33(28,29)31-7-5-17(4-2-15)13-11(14(20)16-3-6-30-32(25,26)27)8-10(18(21)22)9-12(13)19(23)24/h8-9H,2-7H2,1H3,(H,16,20)(H2,25,26,27)
SMILES Code
CS(=O)(OCCN(CCBr)C1=C(C(NCCOP(O)(O)=O)=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O)=O
Appearance
Solid powder
Purity
>95% (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
>5 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
 

Preparing Stock Solutions

The following data is based on the product molecular weight 579.27 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
1: Wurm D, Ewert P, Fierlinger P, Wakai RT, Wallner V, Wunderl L, Wacker-Gußmann A. A Small Scale Optically Pumped Fetal Magnetocardiography System. J Clin Med. 2023 May 10;12(10):3380. doi: 10.3390/jcm12103380. PMID: 37240486; PMCID: PMC10219566. 2: Jackson-Patel V, Liu E, Bull MR, Ashoorzadeh A, Bogle G, Wolfram A, Hicks KO, Smaill JB, Patterson AV. Tissue Pharmacokinetic Properties and Bystander Potential of Hypoxia-Activated Prodrug CP-506 by Agent-Based Modelling. Front Pharmacol. 2022 Feb 8;13:803602. doi: 10.3389/fphar.2022.803602. PMID: 35211015; PMCID: PMC8861431. 3: Abbattista MR, Ashoorzadeh A, Guise CP, Mowday AM, Mittra R, Silva S, Hicks KO, Bull MR, Jackson-Patel V, Lin X, Prosser GA, Lambie NK, Dachs GU, Ackerley DF, Smaill JB, Patterson AV. Restoring Tumour Selectivity of the Bioreductive Prodrug PR-104 by Developing an Analogue Resistant to Aerobic Metabolism by Human Aldo-Keto Reductase 1C3. Pharmaceuticals (Basel). 2021 Nov 26;14(12):1231. doi: 10.3390/ph14121231. PMID: 34959631; PMCID: PMC8707548. 4: Singleton DC, Mowday AM, Guise CP, Syddall SP, Bai SY, Li D, Ashoorzadeh A, Smaill JB, Wilson WR, Patterson AV. Bioreductive prodrug PR-104 improves the tumour distribution and titre of the nitroreductase-armed oncolytic adenovirus ONYX-411NTR leading to therapeutic benefit. Cancer Gene Ther. 2022 Jul;29(7):1021-1032. doi: 10.1038/s41417-021-00409-2. Epub 2021 Nov 26. PMID: 34837065. 5: Li Y, Zhao L, Li XF. Targeting Hypoxia: Hypoxia-Activated Prodrugs in Cancer Therapy. Front Oncol. 2021 Jul 29;11:700407. doi: 10.3389/fonc.2021.700407. PMID: 34395270; PMCID: PMC8358929. 6: Mowday AM, Dubois LJ, Kubiak AM, Chan-Hyams JVE, Guise CP, Ashoorzadeh A, Lambin P, Ackerley DF, Smaill JB, Minton NP, Theys J, Patterson AV. Use of an optimised enzyme/prodrug combination for Clostridia directed enzyme prodrug therapy induces a significant growth delay in necrotic tumours. Cancer Gene Ther. 2022 Feb;29(2):178-188. doi: 10.1038/s41417-021-00296-7. Epub 2021 Feb 8. PMID: 33558701. 7: Mowday AM, Copp JN, Syddall SP, Dubois LJ, Wang J, Lieuwes NG, Biemans R, Ashoorzadeh A, Abbattista MR, Williams EM, Guise CP, Lambin P, Ackerley DF, Smaill JB, Theys J, Patterson AV. E. coli nitroreductase NfsA is a reporter gene for non-invasive PET imaging in cancer gene therapy applications. Theranostics. 2020 Aug 21;10(23):10548-10562. doi: 10.7150/thno.46826. PMID: 32929365; PMCID: PMC7482819. 8: Belhadi J, Ruvalcaba J, Yousfi S, El Marssi M, Cordova T, Matzen S, Lecoeur P, Bouyanfif H. Conduction mechanism and switchable photovoltaic effect in (1 1 1) oriented BiFe0.95Mn0.05O3 thin film. J Phys Condens Matter. 2019 Jul 10;31(27):275701. doi: 10.1088/1361-648X/ab157e. Epub 2019 Apr 2. PMID: 30939455. 9: Stornetta A, Deng KK, Danielli S, Liyanage HDS, Sturla SJ, Wilson WR, Gu Y. Drug-DNA adducts as biomarkers for metabolic activation of the nitro-aromatic nitrogen mustard prodrug PR-104A. Biochem Pharmacol. 2018 Aug;154:64-74. doi: 10.1016/j.bcp.2018.04.004. Epub 2018 Apr 7. PMID: 29630868. 10: Izukura R, Imada H, Hashiguchi N, Sawatari H, Ohguri T, Miyazono M, Ohta S, Takakura C, Yamasaki K, Magota C, Fujita K, Kuroda H, Hirata H, Ohkusa T, Chishaki A. Cardiac and respiratory effects of deep regional hyperthermia using an 8 MHz radiofrequency-capacitive device on patients with cancer. Int J Hyperthermia. 2017 Jun;33(4):428-434. doi: 10.1080/02656736.2017.1283064. Epub 2017 Feb 6. PMID: 28093005. 11: Mowday AM, Ashoorzadeh A, Williams EM, Copp JN, Silva S, Bull MR, Abbattista MR, Anderson RF, Flanagan JU, Guise CP, Ackerley DF, Smaill JB, Patterson AV. Rational design of an AKR1C3-resistant analog of PR-104 for enzyme-prodrug therapy. Biochem Pharmacol. 2016 Sep 15;116:176-87. doi: 10.1016/j.bcp.2016.07.015. Epub 2016 Jul 22. PMID: 27453434. 12: Phillips RM. Targeting the hypoxic fraction of tumours using hypoxia- activated prodrugs. Cancer Chemother Pharmacol. 2016 Mar;77(3):441-57. doi: 10.1007/s00280-015-2920-7. Epub 2016 Jan 25. PMID: 26811177; PMCID: PMC4767869. 13: Fulda S. Biomarker of sensitivity to PR-104 in leukemia. Blood. 2015 Sep 3;126(10):1153-4. doi: 10.1182/blood-2015-07-655225. PMID: 26337349. 14: Moradi Manesh D, El-Hoss J, Evans K, Richmond J, Toscan CE, Bracken LS, Hedrick A, Sutton R, Marshall GM, Wilson WR, Kurmasheva RT, Billups C, Houghton PJ, Smith MA, Carol H, Lock RB. AKR1C3 is a biomarker of sensitivity to PR-104 in preclinical models of T-cell acute lymphoblastic leukemia. Blood. 2015 Sep 3;126(10):1193-202. doi: 10.1182/blood-2014-12-618900. Epub 2015 Jun 26. PMID: 26116659; PMCID: PMC4559932. 15: Abbattista MR, Jamieson SM, Gu Y, Nickel JE, Pullen SM, Patterson AV, Wilson WR, Guise CP. Pre-clinical activity of PR-104 as monotherapy and in combination with sorafenib in hepatocellular carcinoma. Cancer Biol Ther. 2015;16(4):610-22. doi: 10.1080/15384047.2015.1017171. Epub 2015 Apr 14. PMID: 25869917; PMCID: PMC4622463. 16: Konopleva M, Thall PF, Yi CA, Borthakur G, Coveler A, Bueso-Ramos C, Benito J, Konoplev S, Gu Y, Ravandi F, Jabbour E, Faderl S, Thomas D, Cortes J, Kadia T, Kornblau S, Daver N, Pemmaraju N, Nguyen HQ, Feliu J, Lu H, Wei C, Wilson WR, Melink TJ, Gutheil JC, Andreeff M, Estey EH, Kantarjian H. Phase I/II study of the hypoxia-activated prodrug PR104 in refractory/relapsed acute myeloid leukemia and acute lymphoblastic leukemia. Haematologica. 2015 Jul;100(7):927-34. doi: 10.3324/haematol.2014.118455. Epub 2015 Feb 14. PMID: 25682597; PMCID: PMC4486227. 17: Hunter FW, Hsu HL, Su J, Pullen SM, Wilson WR, Wang J. Dual targeting of hypoxia and homologous recombination repair dysfunction in triple-negative breast cancer. Mol Cancer Ther. 2014 Nov;13(11):2501-14. doi: 10.1158/1535-7163.MCT-14-0476. Epub 2014 Sep 5. PMID: 25193512. 18: Hunter FW, Jaiswal JK, Hurley DG, Liyanage HD, McManaway SP, Gu Y, Richter S, Wang J, Tercel M, Print CG, Wilson WR, Pruijn FB. The flavoprotein FOXRED2 reductively activates nitro-chloromethylbenzindolines and other hypoxia- targeting prodrugs. Biochem Pharmacol. 2014 May 15;89(2):224-35. doi: 10.1016/j.bcp.2014.03.001. Epub 2014 Mar 13. PMID: 24632291. 19: Jamieson SM, Gu Y, Manesh DM, El-Hoss J, Jing D, Mackenzie KL, Guise CP, Foehrenbacher A, Pullen SM, Benito J, Smaill JB, Patterson AV, Mulaw MA, Konopleva M, Bohlander SK, Lock RB, Wilson WR. A novel fluorometric assay for aldo-keto reductase 1C3 predicts metabolic activation of the nitrogen mustard prodrug PR-104A in human leukaemia cells. Biochem Pharmacol. 2014 Mar 1;88(1):36-45. doi: 10.1016/j.bcp.2013.12.019. Epub 2014 Jan 13. PMID: 24434189. 20: Foehrenbacher A, Secomb TW, Wilson WR, Hicks KO. Design of optimized hypoxia-activated prodrugs using pharmacokinetic/pharmacodynamic modeling. Front Oncol. 2013 Dec 27;3:314. doi: 10.3389/fonc.2013.00314. PMID: 24409417; PMCID: PMC3873531.