(2-METHOXY-5-[2-(2,4,6-TRIMETHOXY-PHENYL)-ETHENESULFONYLMETHYL]-PHENYLAMINO)-ACETIC ACID, SODIUM SALT

China [CN]

Basic Information

Item | Details

English Name | (2-Methoxy-5-[[(E)-2-(2,4,6-trimethoxyphenyl)ethenyl]sulfonylmethyl]phenyl)amino)acetic acid, sodium salt; Rigosertib Sodium

Chinese Name | Rigosertib Sodium; (2-Methoxy-5-[(E)-2-(2,4,6-trimethoxyphenyl)ethenylsulfonylmethyl]phenyl)aminoacetic acid sodium salt

CAS Number | 592542-60-4

Chemical Synonym | Glycine, N-[2-Methoxy-5-[[[(1E)-2-(2,4,6-triMethoxyphenyl)ethenyl]sulfonyl]Methyl]phenyl]-, sodium salt

Molecular Formula | C₂₁H₂₄NNaO₈S

Molecular Weight | 473.47

Target | PLK1 (Polo-like kinase 1), PI3K (Phosphoinositide 3-kinase), induces tumor cell apoptosis

Development Status | Phase III clinical trials (for myelodysplastic syndromes, acute myeloid leukemia, etc.)

Physicochemical Properties

Parameter | Data

Appearance | White to pale yellow powder

Melting Point | 174–178°C

Solubility | Easily soluble in dimethyl sulfoxide (DMSO), slightly soluble in methanol, sparingly soluble in water

Storage Conditions | Store at -20°C in a sealed container, protected from light and moisture

Chiral Characteristics | Contains an (E)-configured double bond, no chiral center, geometric isomer purity >99%

Dissociation Constant (pKa) | Carboxyl group pKa ≈ 4.5, amino group pKa ≈ 9.2 (predicted value)

Mechanism of Action and Clinical Applications

Core Mechanism: By inhibiting PLK1 (a key cell cycle kinase) and PI3K (a signaling pathway kinase), it blocks the mitotic process of tumor cells, inducing G2/M phase arrest and apoptosis, while also inhibiting tumor angiogenesis.

Clinical Positioning

Indications: Myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), advanced solid tumors (such as pancreatic cancer, ovarian cancer). Dosage and Administration: Intravenous infusion, dosage adjusted according to indication (e.g., for MDS, 1800 mg/m², once daily for 5 consecutive days, 28 days per cycle).

Developer: Onconova Therapeutics.

Pharmacokinetics (Clinical Data)

Parameter Data

Time to peak concentration (Tmax) 0.5 hours after the end of intravenous infusion

Elimination half-life (t₁/₂) Approximately 10–12 hours

Volume of distribution Approximately 15 L/m²

Plasma protein binding rate >95% (primarily bound to albumin)

Metabolic pathway Primarily oxidized by CYP3A4, a small amount glucuronidated by UGT1A9

Excretion pathway Feces (approximately 65%); urine (approximately 30%, mainly metabolites)

Safety and Drug Interactions

Common Adverse Reactions

Hematological system: Neutropenia (35%), thrombocytopenia (28%), anemia (22%).

Non-hematological system: Fatigue (42%), nausea (38%), diarrhea (31%), vomiting (25%), mostly mild to moderate, can be relieved by dose adjustment or symptomatic treatment.

Requires attention: Interstitial lung disease (incidence <2%), liver and kidney function abnormalities (regular monitoring).

Drug Interactions

Strong CYP3A4 inhibitors (e.g., itraconazole): Increase blood drug concentration, requiring dose reduction or extended dosing interval.

Strong CYP3A4 inducers (e.g., rifampicin): Decrease blood drug concentration, reducing efficacy; concomitant use is not recommended.

Anticoagulants (e.g., warfarin): Increase the risk of bleeding, requiring monitoring of coagulation function.