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Products are for research use only. Not for human use. We do not sell to patients.
(ON-01910 sodium; ON01910 sodium; ON01910 sodium)
Rigosertib sodium Chemical Structure
|Product name: Rigosertib sodium|
|Cat. No.: HY-12037|
Rigosertib sodium (ON-01910 sodium) is a non-ATP-competitive inhibitor of PLK1 with IC50 of 9 nM. It shows 30-fold greater selectivity against PLK2 and no activity to PLK3.
IC50 Value: 9 nM 
in vitro: ON 01910.Na induced apoptosis in CLL B cells without significant toxicity against T cells or normal B cells. ON 01910.Na was equally active against leukemic cells associated with a more aggressive disease course [immunoglobulin heavy-chain variable region unmutated, adverse cytogenetics] than against cells without these features. Gene expression profiling revealed two main mechanisms of action: PI3K/AKT inhibition and induction of ROS that resulted in an oxidative stress response through activating protein 1 (AP-1), c-jun-NH(2)-terminal kinase, and ATF3 culminating in the upregulation of NOXA. ROS scavengers and shRNA mediated knockdown of ATF3- and NOXA-protected cells from drug-induced apoptosis . ON 01910.Na caused hyperphosphorylation of RanGAP1·SUMO1 within 4 hours that was sustained for more than 24 hours. ON 01910.Na neither induces DNA damage directly nor acts as a tubulin toxin .
in vivo: ON 01910.Na were assessed after administration (10-150 mg/kg, IP or IV) to several species (mouse, rat, and dog). Plasma protein binding was assessed using ultrafiltration. Patients had solid tumors refractory to standard therapy . ON 01910.Na was administered as a 2-hour infusion on days 1, 4, 8, 11, 15, and 18 in 28-day cycles. The starting dose was 80 mg, and an accelerated titration schedule (single-patient cohorts) was used for escalation. Pharmacokinetics was studied on days 1 and 15 of cycle 1 .
Toxicity: Mean absolute oral bioavailability ranged from 13·9% (fed) to 34·8% (fasting) in 12 patients treated at the 560 mg b.i.d. dose level. Dose-limiting toxicity (grade 3 dysuria and shortness of breath) occurred at the 700 mg b.i.d. dose. Five patients experienced grade 3 non-haematological toxicity, including symptoms of urothelial inflammation, hypotension and syncope, fatigue and abdominal pain .
|M.Wt||473.47||Storage||Please store the product under the recommended conditions in the Certificate of Analysis.|
|Solvent & Solubility||
H2O: ≥ 52 mg/mL
|Product Name||Sponsor Only||Condition||Start Date||End Date||Phase||Last Change Date|
|Rigosertib sodium||Onconova Therapeutics Inc||Myelodysplastic syndrome||31-AUG-13||31-DEC-15||Safety; Efficacy; Pharmacokinetics|
|Onconova Therapeutics Inc||Metastatic pancreas cancer||31-MAY-11||31-DEC-14||Safety; Efficacy; Pharmacokinetics; Pharmacodynamics|
|Onconova Therapeutics Inc||Myelodysplastic syndrome||30-NOV-10||31-DEC-13||Safety; Efficacy|
|Stanford University||Myelodysplastic syndrome||31-MAY-09||28-FEB-11||Safety; Efficacy|
|Onconova Therapeutics Inc||Myelodysplastic syndrome||31-JUL-13||30-JUN-15||Safety; Efficacy|
. Chapman CM, et al. ON 01910.Na is selectively cytotoxic for chronic lymphocytic leukemia cells through a dual mechanism of action involving PI3K/AKT inhibition and induction of oxidative stress. Clin Cancer Res. 2012 Apr 1;18(7):1979-91.
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