Successful, we will reply to you quickly.OK
Please select the quantity.OK
Your message is being sent, please wait.Close
Send mail failed, please send again!Close
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.
BI2536 is a potent Plk1 inhibitor with IC50 of 0.83 nM, BI2536 shows 4- and 11-fold greater selectivity against Plk2 and Plk3; BI2536 also is a BRD4 inhibitor(IC50= 25 nM).
Centrinone is a selective and reversible inhibitor of polo-like kinase 4 (Plk4), a serine-threonine protein kinase that initiates centriole/centrosome assembly.
Centrinone-B is a high affinity and selective PLK4 inhibitor (Ki = 0.59 nM).
GSK461364 is a potent small molecule Polo-like kinase 1 (PLK1) inhibitor with a Ki of 2.2 nM.
GW843682X is a selective PLK1 and PLK3 inhibitor with IC50s of 2.2 nM(PLK1) and 9.1 nM(PLK3); displays > 100-fold selectivity over ~30 other kinases tested including cdk1 and cdk2.
HMN-214(IVX214) is a potent PLK1 inhibitor an average IC50 of 0.12 (mu)M.
LFM-A13 is a potent and selective inhibitor of Btk with IC50 of 17.2 uM; also inhibits PLK3 with IC50 of 7.2 uM.
MLN0905 is a small-molecule and potent inhibitor of PLK1 with IC50 of 2 nM.
NMS-1286937(NMS-P937) is an orally bioavailable, small-molecule Polo-like kinase 1 (PLK1) inhibitor(IC50=2 nM) with potential antineoplastic activity; no inhibition on PLK2 and PLK3.
The phosphoserine/phosphothreonine recognition site of the polo-box domain of polo-like kinase 1 is the binding pocket for thymoquinone and its analogue poloxime. Both small molecules displace phosphopeptides bound with the polo-box domain in a slow but noncovalent binding mode.