U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C21H25NO8S
Molecular Weight 451.492
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of RIGOSERTIB

SMILES

COc1cc(c(/C(/[H])=C(\[H])/S(=O)(=O)Cc2ccc(c(c2)NCC(=O)O)OC)c(c1)OC)OC

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+

HIDE SMILES / InChI

Molecular Formula C21H25NO8S
Molecular Weight 451.492
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 1
Optical Activity NONE

Description
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).

Approval Year

Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
248 μg/mL
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
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
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
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
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
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

AUC

ValueDoseCo-administeredAnalytePopulation
976 μg × h/mL
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
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
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
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
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
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

T1/2

ValueDoseCo-administeredAnalytePopulation
2.3 h
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
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
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
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
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
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

Funbound

ValueDoseCo-administeredAnalytePopulation
2.3%
unknown, unknown
RIGOSERTIB SODIUM plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse 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%)
Hyponatraemia (grade 3, 100%)
Sources: Page: p.44
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%)
Shortness of breath (grade 3, 16.7%)
Sources: Page: p.6, 7, 15
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%)
Hematuria (grade 3, 3%)
Sources: Page: p.17
AEs

AEs

AESignificanceDosePopulation
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
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer




Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
yes [IC50 0.2635 uM]
Drug as victim
PubMed

PubMed

TitleDatePubMed
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
Patents

Sample Use Guides

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
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.
Substance Class Chemical
Created
by admin
on Sat Jun 26 06:15:42 UTC 2021
Edited
by admin
on Sat Jun 26 06:15:42 UTC 2021
Record UNII
67DOW7F9GL
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
RIGOSERTIB
INN   USAN   WHO-DD  
INN   USAN  
Official Name English
RIGOSERTIB [WHO-DD]
Common Name English
RIGOSERTIB [INN]
Common Name English
N-(2-METHOXY-5-((((1E)-2-(2,4,6-TRIMETHOXYPHENYL)ETHENYL)SULFONYL)METHYL)PHENYL)GLYCINE
Systematic Name English
ON 01910
Code English
RIGOSERTIB [USAN]
Common Name English
ON-01910
Code English
Classification Tree Code System Code
NCI_THESAURUS C1404
Created by admin on Sat Jun 26 06:15:42 UTC 2021 , Edited by admin on Sat Jun 26 06:15:42 UTC 2021
FDA ORPHAN DRUG 333611
Created by admin on Sat Jun 26 06:15:42 UTC 2021 , Edited by admin on Sat Jun 26 06:15:42 UTC 2021
FDA ORPHAN DRUG 366412
Created by admin on Sat Jun 26 06:15:42 UTC 2021 , Edited by admin on Sat Jun 26 06:15:42 UTC 2021
FDA ORPHAN DRUG 289409
Created by admin on Sat Jun 26 06:15:42 UTC 2021 , Edited by admin on Sat Jun 26 06:15:42 UTC 2021
Code System Code Type Description
CAS
592542-59-1
Created by admin on Sat Jun 26 06:15:42 UTC 2021 , Edited by admin on Sat Jun 26 06:15:42 UTC 2021
PRIMARY
PUBCHEM
6918736
Created by admin on Sat Jun 26 06:15:42 UTC 2021 , Edited by admin on Sat Jun 26 06:15:42 UTC 2021
PRIMARY
WIKIPEDIA
RIGOSERTIB
Created by admin on Sat Jun 26 06:15:42 UTC 2021 , Edited by admin on Sat Jun 26 06:15:42 UTC 2021
PRIMARY
INN
9516
Created by admin on Sat Jun 26 06:15:42 UTC 2021 , Edited by admin on Sat Jun 26 06:15:42 UTC 2021
PRIMARY
EPA CompTox
592542-59-1
Created by admin on Sat Jun 26 06:15:42 UTC 2021 , Edited by admin on Sat Jun 26 06:15:42 UTC 2021
PRIMARY
EVMPD
SUB36359
Created by admin on Sat Jun 26 06:15:42 UTC 2021 , Edited by admin on Sat Jun 26 06:15:42 UTC 2021
PRIMARY
FDA UNII
67DOW7F9GL
Created by admin on Sat Jun 26 06:15:42 UTC 2021 , Edited by admin on Sat Jun 26 06:15:42 UTC 2021
PRIMARY
DRUG BANK
DB12146
Created by admin on Sat Jun 26 06:15:42 UTC 2021 , Edited by admin on Sat Jun 26 06:15:42 UTC 2021
PRIMARY
NCI_THESAURUS
C152216
Created by admin on Sat Jun 26 06:15:42 UTC 2021 , Edited by admin on Sat Jun 26 06:15:42 UTC 2021
PRIMARY
ChEMBL
CHEMBL1241855
Created by admin on Sat Jun 26 06:15:42 UTC 2021 , Edited by admin on Sat Jun 26 06:15:42 UTC 2021
PRIMARY
Related Record Type Details
ACTIVE MOIETY