Phase 1 study of intravenous rigosertib (ON 01910.Na), a novel benzyl styryl sulfone structure producing G2/M arrest and apoptosis, in adult patients with advanced cancer.

Rigosertib (ON 01910.Na), a synthetic novel benzyl styryl sulfone, was administered to 28 patients with advanced cancer in a Phase I trial in order to characterize its pharmacokinetic profile, determine the dose-limiting toxicities (DLT), define the recommended phase II dose (RPTD) and to document any antitumor activity. Patients with advanced malignant neoplasms refractory to standard therapy were given escalating doses of rigosertib (50, 100, 150, 250, 325, 400, 650, 850, 1,050, 1,375, 1,700 mg/m(2)/24h) as a 3-day continuous infusion (CI) every 2 weeks.

Effect of ON 01910.Na, an anticancer mitotic inhibitor, on cell-cycle progression correlates with RanGAP1 hyperphosphorylation.

The benzyl styryl sulfone, ON 01910.Na, is a novel anticancer agent that inhibits mitotic progression and induces apoptosis in most cancer cell lines. We examined the effect of ON 01910.

Discontinuous drug binding to proteins: binding of an antineoplastic benzyl styryl sulfone to albumin and enzymes in vitro and in phase I clinical trials.

Sodium (E)-{N-[2-methyloxy-5-(2',4',6'-trimethoxy-styrylsulfonyl) methylenephenyl]amino}acetate (C(21)H(24)NNaO(8)S, ON 01910.Na) is a novel, synthetic benzyl styryl sulfone, currently in phase I clinical trials in cancer patients. Our objective was to use electrospray mass spectrometry to determine, in intact complexes, the number of drug molecules bound to albumin and selected enzymes.

[Adenovirus-mediated transfer of anti-MDR1 ribozyme in the treatment of multidrug-resistant human lymphoma in SCID mice].

Objective: To evaluate the effect of adenovirus-mediated transfer of anti-MDR1 ribozyme on restoring drug sensitivity of multidrug-resistant human lymphoma both in vitro and in SCID mice.

Methods: A recombinant adenovirus expressing ribozyme against codon 196 of MDR1 mRNA (Ad-196MDR1-Rz) was developed through cotransfection of shuttle vector pCA14 containing 196MDR1-Rz and rescue vector pJM17 into human embryonic kidney cell line 293. In vitro Daudi/MDR20, a MDR1-mediated drug-resistant human lymphoma cell line, was transduced by Ad-196MDR1-Rz at MOI of 400 pfu/cell.