Rigosertib

Summary

Rigosertib (CHEMBL1241855) is a phase-3 clinical-stage small-molecule microtubule-destabilising agent; indicated across 6 conditions including myelodysplastic syndrome and head and neck squamous cell carcinoma; with CIViC clinical evidence for 1 variant-indication association (e.g. KRAS KRAS4A underexpression in pancreatic cancer).

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• Indications: 6 conditions
• Clinical trials: 15
• Precision-oncology evidence (CIViC): 1 variant–indication association
• Chemistry: 451.5 Da · C21H25NO8S

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL1241855
Name	Rigosertib
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	6918736
ChEBI	CHEBI:145417
Molecular formula	C21H25NO8S
Molecular weight	451.5
InChIKey	OWBFCJROIKNMGD-BQYQJAHWSA-N

SMILES: COC1=C(C=C(C=C1)CS(=O)(=O)/C=C/C2=C(C=C(C=C2OC)OC)OC)NCC(=O)O

IUPAC name: 2-[2-methoxy-5-[[(E)-2-(2,4,6-trimethoxyphenyl)ethenyl]sulfonylmethyl]anilino]acetic acid

ChEBI definition: An N-[2-methoxy-5-({[2-(2,4,6-trimethoxyphenyl)ethenyl]sulfonyl}methyl)phenyl]glycine in which the double bond has E-configuration. It is a non-ATP-competitive inhibitor of PLK1 with an IC50 of 9 nM and exhibits anti-cancer properties.

Pharmacological roles (ChEBI): microtubule-destabilising agent, EC 2.7.11.21 (polo kinase) inhibitor, apoptosis inducer, antineoplastic agent.

Also known as: ON 01910, ON01910, Rigosertib, RIGOSERTIB

Parent form; salt/anhydrous children: CHEMBL2013119

Patent coverage: 597 distinct patent families (1,544 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 1,456 (94%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Broader ChEMBL bioactivity targets: 5 (assay-derived). Sample: Serine/threonine-protein kinase PLK1, Hepatocyte growth factor receptor, Ferrochelatase, mitochondrial, Ribosyldihydronicotinamide dehydrogenase [quinone], Dual specificity protein kinase CLK3.

Bioactivity

ChEMBL activities: 5 potent at pChembl ≥ 5 of 6 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
PLK1	8.05	IC50	9	nM	CHEMBL_ACT_15147438
PLK1	7.82	IC50	15.16	nM	CHEMBL_ACT_25966247
CLK3	7.4	Kd	40	nM	CHEMBL_ACT_17892753
MET	6.03	Kd	940	nM	CHEMBL_ACT_17918993
FECH	5.25	Kd	5577	nM	CHEMBL_ACT_17902542

Target pathways

No target-pathway data for this drug (no mapped target genes).

Indications & clinical

Indications

6 indications (0 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
myelodysplastic syndrome	3	MONDO:0018881	EFO:0000198
myelodysplastic syndrome with excess blasts	3	MONDO:0019454	EFO:0003811
head and neck squamous cell carcinoma	2	MONDO:0010150	EFO:0000181
squamous cell lung carcinoma	2	MONDO:0005097	EFO:0000708
esophageal squamous cell carcinoma	2	MONDO:0005580	EFO:0005922
neoplasm	1	MONDO:0005070	EFO:0000616

Clinical trials

Total trials: 15.

Phase distribution

Phase	Trials
PHASE2	5
PHASE1	5
PHASE1/PHASE2	4
PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02562443	PHASE3	TERMINATED	Controlled Study of Rigosertib Versus Physician’s Choice of Treatment in MDS Patients After Failure of an HMA
NCT05764395	PHASE2	ACTIVE_NOT_RECRUITING	Rigosertib Plus Pembrolizumab in Treating Patients With Unresectable/Metastatic Melanoma Refractory to PD-1 Inhibitors
NCT01167166	PHASE1/PHASE2	COMPLETED	Safety and Efficacy of 72-hour and 120-hour Infusion of Rigosertib in Acute Myeloid Leukemia (AML) and Acute Lymphoid Leukemia (ALL)
NCT01584531	PHASE2	COMPLETED	Efficacy and Safety of Oral Rigosertib in Transfusion-dependent, Low or Int-1 or Trisomy 8 Int-2 Myelodysplastic Syndrome
NCT01807546	PHASE2	COMPLETED	Oral Rigosertib for Squamous Cell Carcinoma
NCT01904682	PHASE2	COMPLETED	Oral Rigosertib in Low Risk MDS Patients Refractory to ESAs
NCT01926587	PHASE1/PHASE2	COMPLETED	Phase II Part 2 Expansion of Oral Rigosertib in Combination With Azacitidine
NCT02730884	PHASE2	TERMINATED	Single-Arm Study of the Efficacy and Safety of Oral Rigosertib in Patients With Myelofibrosis (MF) and Anemia
NCT03786237	PHASE1/PHASE2	COMPLETED	Rigosertib for RDEB-SCC
NCT04263090	PHASE1/PHASE2	COMPLETED	Rigosertib Plus Nivolumab for KRAS+ NSCLC Patients Who Progressed on First-Line Treatment
NCT00861510	PHASE1	COMPLETED	A Pilot Study of the Safety and Activity of Escalating Doses of ON 01910.Na in Patients With Relapsed Mantle Cell Lymphoma, Multiple Myeloma, Chronic Lymphocytic Leukemia, and Related Lymphoid Malignancies
NCT01168011	PHASE1	COMPLETED	Safety, Pharmacokinetics and Clinical Activity of Oral Rigosertib in Solid Tumors
NCT02030639	PHASE1	COMPLETED	Metabolism and Excretion of [14C]-Rigosertib After Infusion to Volunteers
NCT02075034	PHASE1	WITHDRAWN	Three Dosing Schedules of Oral Rigosertib in MDS Patients
NCT02107235	PHASE1	COMPLETED	Platinum-based Chemoradiotherapy and Rigosertib in Head and Neck Cancer

Clinical evidence (CIViC)

Variant × indication × effect (1 predictive associations from 1 curated evidence items):

Variant	Indication	Effect	Therapy	Level	CIViC
KRAS KRAS4A underexpression	Pancreatic Cancer	Resistance	Rigosertib + RG5	CIViC D	EID9602

Pharmacology

Pharmacogenomics

No PharmGKB pharmacogenomic data curated for this drug.

Related molecules

Related molecules

No competitor molecules sharing a primary target (ChEMBL phase ≥2 or PubChem drug-class).