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Chemical Structure| 328087-38-3 Chemical Structure| 328087-38-3

Structure of Phortress
CAS No.: 328087-38-3

Chemical Structure| 328087-38-3

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Aryl Hydrocarbon Receptor (AhR) Agonists, Signal Transduction Modulators

Synonyms: NSC 710305

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Product Citations

Product Citations

Ouellette, Vincent ; Bouzriba, Chahrazed ; Alvarez, Atziri Corin Chavez ; Bruxelles, Quentin ; Hamel-Côté, Geneviève ; Fortin, Sébastien

Abstract: We developed first-in-class antimitotic prodrugs phenyl 4-(2-oxo-alkylimidazolidin-1-yl)benzenesulfonates (PAIB-SOs) bioactivated by cytochrome (CYP) 1A1 that are highly selective toward several breast cancer cells. However, they show sparingly water solubility. Therefore, we replaced their phenyl ring B with a substituted pyridinyl group preparing novel pyridinyl 4-(2-oxo-3-alkylimidazolidin-1-yl)benzenesulfonates (PYRAIB-SOs) and their hydrochloride salts. Our results evidence that PYRAIB-SO hydrochloride salts show higher water solubility compared to their neutral and PAIB-SO counterparts by up to 625-fold. PYRAIB-SOs with a nitrogen atom at position 3 of the pyridinyl ring exhibited strong antiproliferative activity (IC50: 0.03-3.3 µM) and high selectivity (8-> 1250) toward sensitive CYP1A1-positive breast cancer cells and cells stably transfected with CYP1A1. They induce cell cycle arrest in the G2/M phase and disrupt microtubule dynamic assembly. Enzymatic assays confirmed that CYP1A1 metabolizes PYRAIB-SOs into their active form with in vitro hepatic half-lives (55-120 min) in rodent and human liver microsomes. Overall, this will allow to increase drug concentration for in vivo studies.

Keywords: Anticancer agents ; Antimitotics ; Antimicrotubule agents ; CYP1A1-activated prodrugs ; Pyridinyl 4-(2-oxo-alkylimidazolidin-1-yl)benzenesulfonates ; PYRAIB-SOs ; Pyridinyl 4-(2-oxoimidazolidin-1-yl)benzenesulfonates ; PYRIB-SOs ; Phenyl 4-(2-oxo-alkylimidazolidin-1-yl)benzenesulfonates ; PAIB-SOs

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Product Details of Phortress

CAS No. :328087-38-3
Formula : C20H25Cl2FN4OS
M.W : 459.41
SMILES Code : O=C(NC1=CC=C(C2=NC3=CC(F)=CC=C3S2)C=C1C)[C@@H](N)CCCCN.[H]Cl.[H]Cl
Synonyms :
NSC 710305
MDL No. :MFCD06407804

Safety of Phortress

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319
Precautionary Statements:P501-P270-P264-P280-P302+P352-P337+P313-P305+P351+P338-P362+P364-P332+P313-P301+P312+P330

Isoform Comparison

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.18mL

0.44mL

0.22mL

10.88mL

2.18mL

1.09mL

21.77mL

4.35mL

2.18mL

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