For research use only. Not for therapeutic Use.
PR-104 (Cat.No:I008837) is a non-toxic, small-molecule, hypoxia-activated, 3,5-dinitrobenzamide 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 the active DNA-crosslinking mustard species hydroxylamine PR-104H intracellularly 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.
| Catalog Number | I008837 |
| CAS Number | 851627-62-8 |
| Synonyms | PR 104; PR-104; PR104.;2-((2-bromoethyl)(2,4-dinitro-6-((2-(phosphonooxy)ethyl)carbamoyl)phenyl)amino)ethyl methanesulfonate |
| Molecular Formula | C14H20BrN4O12PS |
| Purity | ≥95% |
| Target | DNA Alkylator/Crosslinker |
| Solubility | Soluble in DMSO |
| Storage | 0 - 4 °C for short term, or -20 °C for long term |
| IUPAC Name | 2-[N-(2-bromoethyl)-2,4-dinitro-6-(2-phosphonooxyethylcarbamoyl)anilino]ethyl methanesulfonate |
| InChI | 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) |
| InChIKey | GZSOKPMDWVRVMG-UHFFFAOYSA-N |
| SMILES | CS(=O)(=O)OCCN(CCBr)C1=C(C=C(C=C1C(=O)NCCOP(=O)(O)O)[N+](=O)[O-])[N+](=O)[O-] |
| Reference | </br>1:Rational design of an AKR1C3-resistant analog of PR-104 for enzyme-prodrug therapy. 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.Biochem Pharmacol. 2016 Sep 15;116:176-87. doi: 10.1016/j.bcp.2016.07.015. Epub 2016 Jul 22. PMID: 27453434 </br>2:Biomarker of sensitivity to PR-104 in leukemia. Fulda S.Blood. 2015 Sep 3;126(10):1153-4. doi: 10.1182/blood-2015-07-655225. No abstract available. PMID: 26337349 Free Article</br>3:AKR1C3 is a biomarker of sensitivity to PR-104 in preclinical models of T-cell acute lymphoblastic leukemia. 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.Blood. 2015 Sep 3;126(10):1193-202. doi: 10.1182/blood-2014-12-618900. Epub 2015 Jun 26. PMID: 26116659 Free PMC Article</br>4:Pre-clinical activity of PR-104 as monotherapy and in combination with sorafenib in hepatocellular carcinoma. Abbattista MR, Jamieson SM, Gu Y, Nickel JE, Pullen SM, Patterson AV, Wilson WR, Guise CP.Cancer Biol Ther. 2015;16(4):610-22. doi: 10.1080/15384047.2015.1017171. Epub 2015 Apr 14. PMID: 25869917 Free PMC Article</br>5:The Role of Bystander Effects in the Antitumor Activity of the Hypoxia-Activated Prodrug PR-104. Foehrenbacher A, Patel K, Abbattista MR, Guise CP, Secomb TW, Wilson WR, Hicks KO.Front Oncol. 2013 Oct 7;3:263. doi: 10.3389/fonc.2013.00263. eCollection 2013. PMID: 24109591 Free PMC Article</br>6:PR-104 a bioreductive pre-prodrug combined with gemcitabine or docetaxel in a phase Ib study of patients with advanced solid tumours. McKeage MJ, Jameson MB, Ramanathan RK, Rajendran J, Gu Y, Wilson WR, Melink TJ, Tchekmedyian NS.BMC Cancer. 2012 Oct 25;12:496. doi: 10.1186/1471-2407-12-496. PMID: 23098625 Free PMC Article</br>7:A phase I trial of PR-104, a pre-prodrug of the bioreductive prodrug PR-104A, given weekly to solid tumour patients. McKeage MJ, Gu Y, Wilson WR, Hill A, Amies K, Melink TJ, Jameson MB.BMC Cancer. 2011 Oct 7;11:432. doi: 10.1186/1471-2407-11-432. PMID: 21982454 Free PMC Article</br>8:Pronounced hypoxia in models of murine and human leukemia: high efficacy of hypoxia-activated prodrug PR-104. Benito J, Shi Y, Szymanska B, Carol H, Boehm I, Lu H, Konoplev S, Fang W, Zweidler-McKay PA, Campana D, Borthakur G, Bueso-Ramos C, Shpall E, Thomas DA, Jordan CT, Kantarjian H, Wilson WR, Lock R, Andreeff M, Konopleva M.PLoS One. 2011;6(8):e23108. doi: 10.1371/journal.pone.0023108. Epub 2011 Aug 11. PMID: 21853076 Free PMC Article</br>9:Initial testing of the hypoxia-activated prodrug PR-104 by the pediatric preclinical testing program. Houghton PJ, Lock R, Carol H, Morton CL, Phelps D, Gorlick R, Kolb EA, Keir ST, Reynolds CP, Kang MH, Maris JM, Wozniak AW, Gu Y, Wilson WR, Smith MA.Pediatr Blood Cancer. 2011 Sep;57(3):443-53. doi: 10.1002/pbc.22921. Epub 2010 Dec 27. PMID: 21744473 Free PMC Article</br>10:PR-104 plus sorafenib in patients with advanced hepatocellular carcinoma. Abou-Alfa GK, Chan SL, Lin CC, Chiorean EG, Holcombe RF, Mulcahy MF, Carter WD, Patel K, Wilson WR, Melink TJ, Gutheil JC, Tsao CJ.Cancer Chemother Pharmacol. 2011 Aug;68(2):539-45. doi: 10.1007/s00280-011-1671-3. Epub 2011 May 19. PMID: 21594722 |
