PR-104A

PR-104A (SN 27858) is the alcohol metabolite of phosphate prodrug PR-104. PR-104A is a hypoxia-selective DNA cross-linking agent/DNA-damaging agent and cytotoxin. Antitumor Activity. PR-104A is metabolized under hypoxia by the 1-electron NADPH:cytochrome P450 oxidoreductase. PR-104A can be used for the research of relapsed/refractory T-lineage acute lymphoblastic leukemia (T-ALL).

Product information

CAS Number: 680199-06-8

Molecular Weight: 499.29

Formula: C14H19BrN4O9S

Chemical Name: 2-[(2-bromoethyl)({2-[(2-hydroxyethyl)carbamoyl]-4,6-dinitrophenyl})amino]ethyl methanesulfonate

Smiles: CS(=O)(=O)OCCN(CCBr)C1=C(C=C(C=C1[N+]([O-])=O)[N+]([O-])=O)C(=O)NCCO

InChiKey: AZICEEZSDKZDHX-UHFFFAOYSA-N

InChi: 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)

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: Soluble in DMSO

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

PR-104A (1-100 uM) shows antiproliferative potency in a panel of 10 human carcinoma cell lines following 4 hours exposures under aerobic and hypoxic conditions with the lowest IC50 (0.51 μM) in H460 non–small cell lung cancer cells and highest (7.3 μM) in PC3 prostate cells.

In Vivo:

The phosphate ester “pre-prodrug” PR-104 is well tolerated in mice and converted rapidly to the corresponding prodrug PR-104A. H460 xenografts shows significant sensitivity to PR-104 (total dose 3.2 mmol/kg).

References:

1. Adam V Patterson, et al. Mechanism of action and preclinical antitumor activity of the novel hypoxia-activated DNA cross-linking agent PR-104. Clin Cancer Res. 2007 Jul 1;13(13):3922-32.
2. Donya Moradi Manesh, et al. 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.

Products are for research use only. Not for human use.