Drug Information

Drug (ID: DG01497) and It's Reported Resistant Information

• Name: Rigosertib
• Synonyms: Rigosertib; 592542-59-1; UNII-67DOW7F9GL; ON 01910; ON-01910; 67DOW7F9GL; 2-[2-methoxy-5-[[(E)-2-(2,4,6-trimethoxyphenyl)ethenyl]sulfonylmethyl]anilino]acetic acid; (E)-2-((2-methoxy-5-(((2,4,6-trimethoxystyryl)sulfonyl)methyl)phenyl)amino)acetic acid; N-[2-Methoxy-5-({[(E)-2-(2,4,6-Trimethoxyphenyl)ethenyl]sulfonyl}methyl)phenyl]glycine; ON-01910.Na; Rigosertib [USAN:INN]; rigosertibum; 6FS; Rigosertib (USAN); Estybon (proposed trade name); SCHEMBL498623; SCHEMBL498624; GTPL7833; CHEMBL1241855; ON01910.Na; DTXSID30207984; 2-[2-methoxy-5-[2-(2,4,6-trimethoxyphenyl)ethenylsulfonylmethyl]anilino]acetic acid; CHEBI:124939; CHEBI:145417; BCP08296; EX-A4346; ZINC3942646; 4006AH; BDBM50060917; AKOS015966442; DB12146; N-[2-Methoxy-5-[[[(1E)-2-(2,4,6-trimethoxyphenyl)ethenyl]sulfonyl]methyl]phenyl]glycine; (E)-ON 01910; 2-[[2-methoxy-5-[[(E)-2-(2,4,6-trimethoxyphenyl)ethenyl]sulfonylmethyl]phenyl]amino]acetic Acid; AC-32479; AS-35249; ON-01910ON-01910; D10154; ON-01910;ON01910;ON 01910; BRD-K55187425-236-01-1; Q21099552; (e)-2-(5-((2,4,6-trimethoxystyrylsulfonyl)methyl)-2-methoxyphenylamino)acetic acid; [2-methoxy-5-({[(E)-2-(2,4,6-trimethoxyphenyl)ethenyl]sulfonyl}methyl)anilino]acetic acid; [2-methoxy-5-({[2-(2,4,6-trimethoxyphenyl)ethenyl]sulfonyl}methyl)anilino]acetic acid; N-(2-Methoxy-5-((((1E)-2-(2,4,6-trimethoxyphenyl)ethenyl)sulfonyl)methyl) phenyl)glycine; N-[2-methoxy-5-({[2-(2,4,6-trimethoxyphenyl)ethenyl]sulfonyl}methyl)phenyl]glycine; Glycine, N-(2-methoxy-5-((((1E)-2-(2,4,6-trimethoxyphenyl)ethenyl)sulfonyl) methyl)phenyl)-; Glycine, N-[2-Methoxy-5-[[[(1E)-2-(2,4,6-triMethoxyphenyl)ethenyl]sulfonyl]Methyl]phenyl]-; ON-01910; ; ; 2-[2-Methoxy-5-[[(E)-2-(2,4,6-trimethoxyphenyl)ethenyl]sulfonylmethyl]anilino]acetic acid
• Indication:
  In total 3 Indication(s)
  Kidney disease [ICD-11: GC2Z]; Phase 3; [1]
  Lupus nephritis [ICD-11: 4A40]; Phase 3; [1]
  Psoriasis vulgaris [ICD-11: EA90]; Phase 3; [1]
• Target: Calcineurin (PPP3CA); PP2BA_HUMAN; [1]
• Formula: 11
• IsoSMILES: COC1=C(C=C(C=C1)CS(=O)(=O)/C=C/C2=C(C=C(C=C2OC)OC)OC)NCC(=O)O
• InChI: 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+
• InChIKey: OWBFCJROIKNMGD-BQYQJAHWSA-N
• PubChem CID: 6918736
• ChEBI ID: CHEBI:124939
• TTD Drug ID: D0L9HX
• DrugBank ID: DB12146

Type(s) of Resistant Mechanism of This Drug

  ADTT: Aberration of the Drug's Therapeutic Target

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-02: Benign/in-situ/malignant neoplasm

Solid tumour/cancer [ICD-11: 2A00-2F9Z]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: GTPase Hras (HRAS) [1]

• Molecule Alteration: Missense mutation; p.G12V (c.35G>T)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: RAS/RAF/MEK/ERK signaling pathway; Inhibition; hsa01521
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• In Vitro Model: Hela cells; Cervix uteri; Homo sapiens (Human); CVCL_0030
• In Vitro Model: A431 cells; Skin; Homo sapiens (Human); CVCL_0037
• In Vitro Model: HEK293T cells; Kidney; Homo sapiens (Human); CVCL_0063
• In Vitro Model: MIA PaCa-2 cells; Pancreas; Homo sapiens (Human); CVCL_0428
• In Vitro Model: WM1617 cells; Lymph node; Homo sapiens (Human); CVCL_6791
• In Vivo Model: Female nu/nu mouse PDX model; Mus musculus
• Mechanism Description: Rigosertib, a styryl-benzyl sulfone, acts as a RAS-mimetic and interacts with the RBDs of RAF kinases, resulting in their inability to bind to RAS, disruption of RAF activation, and inhibition of the RAS-RAF-MEK pathway. We also find that rigosertib binds to the RBDs of Ral-GDS and PI3Ks.

Key Molecule: PI3-kinase alpha (PIK3CA) [1]

• Molecule Alteration: Missense mutation; p.E545K (c.1633G>A)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: RAS/RAF/MEK/ERK signaling pathway; Inhibition; hsa01521
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• In Vitro Model: Hela cells; Cervix uteri; Homo sapiens (Human); CVCL_0030
• In Vitro Model: A431 cells; Skin; Homo sapiens (Human); CVCL_0037
• In Vitro Model: HEK293T cells; Kidney; Homo sapiens (Human); CVCL_0063
• In Vitro Model: MIA PaCa-2 cells; Pancreas; Homo sapiens (Human); CVCL_0428
• In Vitro Model: WM1617 cells; Lymph node; Homo sapiens (Human); CVCL_6791
• In Vivo Model: Female nu/nu mouse PDX model; Mus musculus
• Mechanism Description: Rigosertib, a styryl-benzyl sulfone, acts as a RAS-mimetic and interacts with the RBDs of RAF kinases, resulting in their inability to bind to RAS, disruption of RAF activation, and inhibition of the RAS-RAF-MEK pathway. We also find that rigosertib binds to the RBDs of Ral-GDS and PI3Ks.

Key Molecule: PI3-kinase alpha (PIK3CA) [1]

• Molecule Alteration: Missense mutation; p.H1047R (c.3140A>G)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: RAS/RAF/MEK/ERK signaling pathway; Inhibition; hsa01521
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• In Vitro Model: Hela cells; Cervix uteri; Homo sapiens (Human); CVCL_0030
• In Vitro Model: A431 cells; Skin; Homo sapiens (Human); CVCL_0037
• In Vitro Model: HEK293T cells; Kidney; Homo sapiens (Human); CVCL_0063
• In Vitro Model: MIA PaCa-2 cells; Pancreas; Homo sapiens (Human); CVCL_0428
• In Vitro Model: WM1617 cells; Lymph node; Homo sapiens (Human); CVCL_6791
• In Vivo Model: Female nu/nu mouse PDX model; Mus musculus
• Mechanism Description: Rigosertib, a styryl-benzyl sulfone, acts as a RAS-mimetic and interacts with the RBDs of RAF kinases, resulting in their inability to bind to RAS, disruption of RAF activation, and inhibition of the RAS-RAF-MEK pathway. We also find that rigosertib binds to the RBDs of Ral-GDS and PI3Ks.

Head and neck cancer [ICD-11: 2D42]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: PI3-kinase alpha (PIK3CA) [2]

• Molecule Alteration: Missense mutation; p.E545K (c.1633G>A)
• Sensitive Disease: Head and neck squamous cell carcinoma [ICD-11: 2D42.1]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HNSCC cells; Neck; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: Sulforhodamine B colorimetric assay
• Mechanism Description: The missense mutation p.E545K (c.1633G>A) in gene PIK3CA cause the sensitivity of Rigosertib by aberration of the drug's therapeutic target

References

• Ref 1: A Small Molecule RAS-Mimetic Disrupts RAS Association with Effector Proteins to Block SignalingCell. 2016 Apr 21;165(3):643-55. doi: 10.1016/j.cell.2016.03.045.
• Ref 2: The dual pathway inhibitor rigosertib is effective in direct patient tumor xenografts of head and neck squamous cell carcinomasMol Cancer Ther. 2013 Oct;12(10):1994-2005. doi: 10.1158/1535-7163.MCT-13-0206. Epub 2013 Jul 19.