Details
Stereochemistry | ACHIRAL |
Molecular Formula | C21H25NO8S |
Molecular Weight | 451.49 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 1 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
COC1=CC(OC)=C(\C=C\S(=O)(=O)CC2=CC=C(OC)C(NCC(O)=O)=C2)C(OC)=C1
InChI
InChIKey=OWBFCJROIKNMGD-BQYQJAHWSA-N
InChI=1S/C21H25NO8S/c1-27-15-10-19(29-3)16(20(11-15)30-4)7-8-31(25,26)13-14-5-6-18(28-2)17(9-14)22-12-21(23)24/h5-11,22H,12-13H2,1-4H3,(H,23,24)/b8-7+
DescriptionCurator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/15766665 | http://www.onconova.com/pipeline/#tab-id-2
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/15766665 | http://www.onconova.com/pipeline/#tab-id-2
Rigosertib sodium (ON 01910.Na) is a small molecule inhibitor of critical pathways important in the growth and survival of cancer cells, being developed by Onconova Therapeutics ("Onconova") for the treatment of hematologic malignancies and solid tumors. Rigosertib (ON-01910) is a non-ATP-competitive inhibitor of PLK1 with IC50 of 9 nM in a cell-free assay. It shows 30-fold greater selectivity against Plk2 and no activity to Plk3. Extensive Phase I and Phase II studies with rigosertib have been conducted at leading institutions in the U.S. and abroad in more than 450 patients with solid tumors and hematological cancers, including MDS and AML. MDS and AML are blood disorders widely recognized as difficult to manage, with limited therapeutic options available for patients, especially those with drug-resistant disease. The multi-site Phase III ONTIME trial in MDS patients is under a Special Protocol Assessment (SPA) from the U.S. FDA and is being supported by an award from the Therapeutics Acceleration Program (TAP) of the Leukemia and Lymphoma Society (LLS). FDA has granted Orphan Drug Designation for the use of rigosertib in MDS. The clinical program in solid tumors is also advancing with initiation of the Phase II/III combination ONTRAC trial (ON 01910.Na TRial in Patients with Advanced Pancreatic Cancer) and Phase II single agent trial in ovarian cancer. In Japan, SymBio is developing rigosertib for the treatment of refractory/relapsed HR-MDS (IV form) and first-line LR-MDS (oral form).
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
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Target ID: CHEMBL3024 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15766665 |
9.0 nM [IC50] | ||
Conditions
Condition | Modality | Targets | Highest Phase | Product |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
248 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24947095 |
3200 mg 2 times / week steady-state, intravenous dose: 3200 mg route of administration: Intravenous experiment type: STEADY-STATE co-administered: |
RIGOSERTIB SODIUM plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
5.93 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24493827 |
700 mg 2 times / day multiple, oral dose: 700 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
RIGOSERTIB SODIUM plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
2.34 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24493827 |
700 mg 2 times / day steady-state, oral dose: 700 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
RIGOSERTIB SODIUM plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
2.54 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24493827 |
560 mg 2 times / day steady-state, oral dose: 560 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
RIGOSERTIB SODIUM plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
4.04 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24493827 |
560 mg 2 times / day multiple, oral dose: 560 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
RIGOSERTIB SODIUM plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
210 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24947095 |
4000 mg 2 times / week multiple, intravenous dose: 4000 mg route of administration: Intravenous experiment type: MULTIPLE co-administered: |
RIGOSERTIB SODIUM plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
976 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24947095 |
3200 mg 2 times / week steady-state, intravenous dose: 3200 mg route of administration: Intravenous experiment type: STEADY-STATE co-administered: |
RIGOSERTIB SODIUM plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
19.58 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24493827 |
700 mg 2 times / day multiple, oral dose: 700 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
RIGOSERTIB SODIUM plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
4.96 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24493827 |
700 mg 2 times / day steady-state, oral dose: 700 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
RIGOSERTIB SODIUM plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
6.99 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24493827 |
560 mg 2 times / day steady-state, oral dose: 560 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
RIGOSERTIB SODIUM plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
9.32 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24493827 |
560 mg 2 times / day multiple, oral dose: 560 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
RIGOSERTIB SODIUM plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
997 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24947095 |
4000 mg 2 times / week multiple, intravenous dose: 4000 mg route of administration: Intravenous experiment type: MULTIPLE co-administered: |
RIGOSERTIB SODIUM plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
2.3 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24947095 |
3200 mg 2 times / week steady-state, intravenous dose: 3200 mg route of administration: Intravenous experiment type: STEADY-STATE co-administered: |
RIGOSERTIB SODIUM plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
3.09 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24493827 |
700 mg 2 times / day multiple, oral dose: 700 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
RIGOSERTIB SODIUM plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
1.99 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24493827 |
700 mg 2 times / day steady-state, oral dose: 700 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
RIGOSERTIB SODIUM plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
4.03 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24493827 |
560 mg 2 times / day steady-state, oral dose: 560 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
RIGOSERTIB SODIUM plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
2.42 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24493827 |
560 mg 2 times / day multiple, oral dose: 560 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
RIGOSERTIB SODIUM plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
1.5 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24947095 |
4000 mg 2 times / week multiple, intravenous dose: 4000 mg route of administration: Intravenous experiment type: MULTIPLE co-administered: |
RIGOSERTIB SODIUM plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
Funbound
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
2.3% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/19466411 |
unknown, unknown |
RIGOSERTIB SODIUM plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
Doses
Dose | Population | Adverse events |
---|---|---|
4200 mg 2 times / week steady-state, intravenous Highest studied dose Dose: 4200 mg, 2 times / week Route: intravenous Route: steady-state Dose: 4200 mg, 2 times / week Sources: Page: p.44 |
unhealthy, ADULT n = 1 Health Status: unhealthy Condition: gastric carcinoma Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 1 Sources: Page: p.44 |
DLT: Asphyxia, Hyponatraemia... Dose limiting toxicities: Asphyxia (grade 5, 100%) Sources: Page: p.44Hyponatraemia (grade 3, 100%) |
700 mg 2 times / day multiple, oral Highest studied dose Dose: 700 mg, 2 times / day Route: oral Route: multiple Dose: 700 mg, 2 times / day Sources: Page: p.6, 7, 15 |
unhealthy, ADULT n = 6 Health Status: unhealthy Condition: myelodysplastic syndrome Age Group: ADULT Sex: M+F Food Status: FASTED Population Size: 6 Sources: Page: p.6, 7, 15 |
DLT: Dysuria, Shortness of breath... Dose limiting toxicities: Dysuria (grade 3, 16.7%) Sources: Page: p.6, 7, 15Shortness of breath (grade 3, 16.7%) |
700 mg 2 times / day multiple, oral Highest studied dose Dose: 700 mg, 2 times / day Route: oral Route: multiple Dose: 700 mg, 2 times / day Sources: Page: p.17 |
unhealthy, ADULT n = 6 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: FASTED Population Size: 6 Sources: Page: p.17 |
DLT: Hematuria... Dose limiting toxicities: Hematuria (grade 3, 16.7%) Sources: Page: p.17 |
3200 mg 2 times / week steady-state, intravenous MTD Dose: 3200 mg, 2 times / week Route: intravenous Route: steady-state Dose: 3200 mg, 2 times / week Sources: Page: p.41, 44 |
unhealthy, ADULT n = 4 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 4 Sources: Page: p.41, 44 |
DLT: Hepatic encephalopathy... Dose limiting toxicities: Hepatic encephalopathy (grade 5, 25%) Sources: Page: p.41, 44 |
560 mg 2 times / day multiple, oral MTD Dose: 560 mg, 2 times / day Route: oral Route: multiple Dose: 560 mg, 2 times / day Sources: Page: p.6, 7, 15 |
unhealthy, ADULT n = 24 Health Status: unhealthy Condition: myelodysplastic syndrome Age Group: ADULT Sex: M+F Food Status: FASTED Population Size: 24 Sources: Page: p.6, 7, 15 |
|
560 mg 2 times / day multiple, oral MTD Dose: 560 mg, 2 times / day Route: oral Route: multiple Dose: 560 mg, 2 times / day Sources: Page: p.17 |
unhealthy, ADULT n = 33 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: FASTED Population Size: 33 Sources: Page: p.17 |
DLT: Dysuria, Hematuria... Dose limiting toxicities: Dysuria (grade 3, 6%) Sources: Page: p.17Hematuria (grade 3, 3%) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Hyponatraemia | grade 3, 100% DLT, Disc. AE |
4200 mg 2 times / week steady-state, intravenous Highest studied dose Dose: 4200 mg, 2 times / week Route: intravenous Route: steady-state Dose: 4200 mg, 2 times / week Sources: Page: p.44 |
unhealthy, ADULT n = 1 Health Status: unhealthy Condition: gastric carcinoma Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 1 Sources: Page: p.44 |
Asphyxia | grade 5, 100% DLT, Disc. AE |
4200 mg 2 times / week steady-state, intravenous Highest studied dose Dose: 4200 mg, 2 times / week Route: intravenous Route: steady-state Dose: 4200 mg, 2 times / week Sources: Page: p.44 |
unhealthy, ADULT n = 1 Health Status: unhealthy Condition: gastric carcinoma Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 1 Sources: Page: p.44 |
Dysuria | grade 3, 16.7% DLT |
700 mg 2 times / day multiple, oral Highest studied dose Dose: 700 mg, 2 times / day Route: oral Route: multiple Dose: 700 mg, 2 times / day Sources: Page: p.6, 7, 15 |
unhealthy, ADULT n = 6 Health Status: unhealthy Condition: myelodysplastic syndrome Age Group: ADULT Sex: M+F Food Status: FASTED Population Size: 6 Sources: Page: p.6, 7, 15 |
Shortness of breath | grade 3, 16.7% DLT |
700 mg 2 times / day multiple, oral Highest studied dose Dose: 700 mg, 2 times / day Route: oral Route: multiple Dose: 700 mg, 2 times / day Sources: Page: p.6, 7, 15 |
unhealthy, ADULT n = 6 Health Status: unhealthy Condition: myelodysplastic syndrome Age Group: ADULT Sex: M+F Food Status: FASTED Population Size: 6 Sources: Page: p.6, 7, 15 |
Hematuria | grade 3, 16.7% DLT, Disc. AE |
700 mg 2 times / day multiple, oral Highest studied dose Dose: 700 mg, 2 times / day Route: oral Route: multiple Dose: 700 mg, 2 times / day Sources: Page: p.17 |
unhealthy, ADULT n = 6 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: FASTED Population Size: 6 Sources: Page: p.17 |
Hepatic encephalopathy | grade 5, 25% DLT, Disc. AE |
3200 mg 2 times / week steady-state, intravenous MTD Dose: 3200 mg, 2 times / week Route: intravenous Route: steady-state Dose: 3200 mg, 2 times / week Sources: Page: p.41, 44 |
unhealthy, ADULT n = 4 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 4 Sources: Page: p.41, 44 |
Hematuria | grade 3, 3% DLT |
560 mg 2 times / day multiple, oral MTD Dose: 560 mg, 2 times / day Route: oral Route: multiple Dose: 560 mg, 2 times / day Sources: Page: p.17 |
unhealthy, ADULT n = 33 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: FASTED Population Size: 33 Sources: Page: p.17 |
Dysuria | grade 3, 6% DLT |
560 mg 2 times / day multiple, oral MTD Dose: 560 mg, 2 times / day Route: oral Route: multiple Dose: 560 mg, 2 times / day Sources: Page: p.17 |
unhealthy, ADULT n = 33 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: FASTED Population Size: 33 Sources: Page: p.17 |
PubMed
Title | Date | PubMed |
---|---|---|
BI 2536, a potent and selective inhibitor of polo-like kinase 1, inhibits tumor growth in vivo. | 2007 Feb 20 |
|
Discovery of a clinical stage multi-kinase inhibitor sodium (E)-2-{2-methoxy-5-[(2',4',6'-trimethoxystyrylsulfonyl)methyl]phenylamino}acetate (ON 01910.Na): synthesis, structure-activity relationship, and biological activity. | 2011 Sep 22 |
|
In vitro antitumor mechanism of (E)-N-(2-methoxy-5-(((2,4,6-trimethoxystyryl)sulfonyl)methyl)pyridin-3-yl)methanesulfonamide. | 2015 Jan |
Sample Use Guides
In Vivo Use Guide
Sources: https://clinicaltrials.gov/ct2/show/NCT01928537
Rigosertib sodium will be administered as a 72-hr continuous intravenous infusion consisting of 3 consecutive doses of 1800 mg over 24 hours on Days 1, 2, and 3 of a 14-day cycle for the first 8 cycles and then on Days 1, 2, and 3 of a 28-day cycle for the following cycles.
Route of Administration:
Intravenous
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/15766665
Rigosertib sodium shows cell killing activity against 94 different tumor cell lines with IC50 of 50-250 nM, including BT27, MCF-7, DU145, PC3, U87, A549, H187, RF1, HCT15, SW480, and KB cells. In HeLa cells, Rigosertib sodium (100-250 nM) induces spindle abnormalities and apoptosis.
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Classification Tree | Code System | Code | ||
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FDA ORPHAN DRUG |
333611
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NCI_THESAURUS |
C1404
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FDA ORPHAN DRUG |
289409
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FDA ORPHAN DRUG |
366412
Created by
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592542-59-1
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6918736
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RIGOSERTIB
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9516
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DTXSID30207984
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XX-89
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SUB36359
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67DOW7F9GL
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100000128814
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145417
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DB12146
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C152216
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CHEMBL1241855
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ACTIVE MOIETY
SALT/SOLVATE (PARENT)