MedKoo Biosciences, Inc.
Tel:   +1-919-636-5577    Fax:   +1-919-980-4831    Email:   sales@medkoo.com
Search
Login Register
Search
MedKoo Cat#: 525643 | Name: PR-104A

Description:

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

PR-104A is a novel hypoxia-targeted anticancer agent, showing modest but significant selectivity for anoxic cells.

Chemical Structure

PR-104A
PR-104A
CAS#680199-06-8

Theoretical Analysis

MedKoo Cat#: 525643

Name: PR-104A

CAS#: 680199-06-8

Chemical Formula: C14H19BrN4O9S

Exact Mass: 498.0056

Molecular Weight: 499.29

Elemental Analysis: C, 33.68; H, 3.84; Br, 16.00; N, 11.22; O, 28.84; S, 6.42

Price and Availability

This product is currently not in stock but may be available through custom synthesis. To ensure cost efficiency, the minimum order quantity is 1 gram. The estimated lead time is 2 to 4 months, with pricing dependent on the complexity of the synthesis (typically high for intricate chemistries). Quotes for quantities below 1 gram will not be provided. To request a quote, please click the button below. Note: If this product becomes available in stock in the future, pricing will be listed accordingly.
Bulk Inquiry
Related CAS #
No Data
Synonym
PR-104A
IUPAC/Chemical Name
2-[N-(2-Bromoethyl)-2-(2-hydroxyethylcarbamoyl)-4,6-dinitroanilino]ethyl methanesulfonate
InChi Key
AZICEEZSDKZDHX-UHFFFAOYSA-N
InChi Code
InChI=1S/C14H19BrN4O9S/c1-29(26,27)28-7-5-17(4-2-15)13-11(14(21)16-3-6-20)8-10(18(22)23)9-12(13)19(24)25/h8-9,20H,2-7H2,1H3,(H,16,21)
SMILES Code
CS(=O)(OCCN(CCBr)C1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1C(NCCO)=O)=O
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
>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

Preparing Stock Solutions

The following data is based on the product molecular weight 499.29 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: Copp JN, Mowday AM, Williams EM, Guise CP, Ashoorzadeh A, Sharrock AV, Flanagan JU, Smaill JB, Patterson AV, Ackerley DF. Engineering a Multifunctional Nitroreductase for Improved Activation of Prodrugs and PET Probes for Cancer Gene Therapy. Cell Chem Biol. 2017 Mar 16;24(3):391-403. doi: 10.1016/j.chembiol.2017.02.005. Epub 2017 Mar 2. PubMed PMID: 28262557. 2: 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. PubMed PMID: 27453434. 3: Erzinger MM, Bovet C, Hecht KM, Senger S, Winiker P, Sobotzki N, Cristea S, Beerenwinkel N, Shay JW, Marra G, Wollscheid B, Sturla SJ. Sulforaphane Preconditioning Sensitizes Human Colon Cancer Cells towards the Bioreductive Anticancer Prodrug PR-104A. PLoS One. 2016 Mar 7;11(3):e0150219. doi: 10.1371/journal.pone.0150219. eCollection 2016. PubMed PMID: 26950072; PubMed Central PMCID: PMC4780774. 4: 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. PubMed PMID: 26116659; PubMed Central PMCID: PMC4559932. 5: 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. PubMed PMID: 25869917; PubMed Central PMCID: PMC4622463. 6: 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. PubMed PMID: 25682597; PubMed Central PMCID: PMC4486227. 7: 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. PubMed PMID: 24632291. 8: 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. PubMed PMID: 24434189. 9: 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. Review. PubMed PMID: 24409417; PubMed Central PMCID: PMC3873531. 10: Green LK, Storey MA, Williams EM, Patterson AV, Smaill JB, Copp JN, Ackerley DF. The Flavin Reductase MsuE Is a Novel Nitroreductase that Can Efficiently Activate Two Promising Next-Generation Prodrugs for Gene-Directed Enzyme Prodrug Therapy. Cancers (Basel). 2013 Aug 8;5(3):985-97. doi: 10.3390/cancers5030985. PubMed PMID: 24202330; PubMed Central PMCID: PMC3795375. 11: Su J, Gu Y, Pruijn FB, Smaill JB, Patterson AV, Guise CP, Wilson WR. Zinc finger nuclease knock-out of NADPH:cytochrome P450 oxidoreductase (POR) in human tumor cell lines demonstrates that hypoxia-activated prodrugs differ in POR dependence. J Biol Chem. 2013 Dec 27;288(52):37138-53. doi: 10.1074/jbc.M113.505222. Epub 2013 Nov 6. PubMed PMID: 24196959; PubMed Central PMCID: PMC3873569. 12: Foehrenbacher A, Patel K, Abbattista MR, Guise CP, Secomb TW, Wilson WR, Hicks KO. The Role of Bystander Effects in the Antitumor Activity of the Hypoxia-Activated Prodrug PR-104. Front Oncol. 2013 Oct 7;3:263. doi: 10.3389/fonc.2013.00263. eCollection 2013. PubMed PMID: 24109591; PubMed Central PMCID: PMC3791487. 13: Su J, Guise CP, Wilson WR. FSL-61 is a 6-nitroquinolone fluorogenic probe for one-electron reductases in hypoxic cells. Biochem J. 2013 May 15;452(1):79-86. doi: 10.1042/BJ20121695. PubMed PMID: 23480813. 14: Prosser GA, Copp JN, Mowday AM, Guise CP, Syddall SP, Williams EM, Horvat CN, Swe PM, Ashoorzadeh A, Denny WA, Smaill JB, Patterson AV, Ackerley DF. Creation and screening of a multi-family bacterial oxidoreductase library to discover novel nitroreductases that efficiently activate the bioreductive prodrugs CB1954 and PR-104A. Biochem Pharmacol. 2013 Apr 15;85(8):1091-103. doi: 10.1016/j.bcp.2013.01.029. Epub 2013 Feb 8. PubMed PMID: 23399641. 15: McKeage MJ, Jameson MB, Ramanathan RK, Rajendran J, Gu Y, Wilson WR, Melink TJ, Tchekmedyian NS. PR-104 a bioreductive pre-prodrug combined with gemcitabine or docetaxel in a phase Ib study of patients with advanced solid tumours. BMC Cancer. 2012 Oct 25;12:496. doi: 10.1186/1471-2407-12-496. PubMed PMID: 23098625; PubMed Central PMCID: PMC3495895. 16: Hunter FW, Wang J, Patel R, Hsu HL, Hickey AJ, Hay MP, Wilson WR. Homologous recombination repair-dependent cytotoxicity of the benzotriazine di-N-oxide CEN-209: comparison with other hypoxia-activated prodrugs. Biochem Pharmacol. 2012 Mar 1;83(5):574-85. doi: 10.1016/j.bcp.2011.12.005. Epub 2011 Dec 13. PubMed PMID: 22182429. 17: Guise CP, Abbattista MR, Tipparaju SR, Lambie NK, Su J, Li D, Wilson WR, Dachs GU, Patterson AV. Diflavin oxidoreductases activate the bioreductive prodrug PR-104A under hypoxia. Mol Pharmacol. 2012 Jan;81(1):31-40. doi: 10.1124/mol.111.073759. Epub 2011 Oct 7. PubMed PMID: 21984255. 18: McKeage MJ, Gu Y, Wilson WR, Hill A, Amies K, Melink TJ, Jameson MB. A phase I trial of PR-104, a pre-prodrug of the bioreductive prodrug PR-104A, given weekly to solid tumour patients. BMC Cancer. 2011 Oct 7;11:432. doi: 10.1186/1471-2407-11-432. PubMed PMID: 21982454; PubMed Central PMCID: PMC3205073. 19: 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. Initial testing of the hypoxia-activated prodrug PR-104 by the pediatric preclinical testing program. Pediatr Blood Cancer. 2011 Sep;57(3):443-53. doi: 10.1002/pbc.22921. Epub 2010 Dec 27. PubMed PMID: 21744473; PubMed Central PMCID: PMC4304205. 20: 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. PR-104 plus sorafenib in patients with advanced hepatocellular carcinoma. Cancer Chemother Pharmacol. 2011 Aug;68(2):539-45. doi: 10.1007/s00280-011-1671-3. Epub 2011 May 19. PubMed PMID: 21594722.

View History

PR-825

PR-825