Drug Information

Drug (ID: DG01566) and It's Reported Resistant Information

• Name: Refametinib
• Synonyms: Refametinib; 923032-37-5; RDEA119; RDEA 119; BAY 869766; UNII-JPX07AFM0N; (S)-N-(3,4-difluoro-2-((2-fluoro-4-iodophenyl)amino)-6-methoxyphenyl)-1-(2,3-dihydroxypropyl)cyclopropane-1-sulfonamide; JPX07AFM0N; Refametinib (RDEA119); BAY-869766; BAY 8697661; Refametinib (RDEA119, Bay 86-9766); N-[3,4-difluoro-2-(2-fluoro-4-iodoanilino)-6-methoxyphenyl]-1-[(2S)-2,3-dihydroxypropyl]cyclopropane-1-sulfonamide; Refametinib R enantiomer; Refametinib [INN]; BAY 86-9766; RDEA-119; 3e8n; BAY 86-97661; Refametinib; RDEA119; SCHEMBL345333; C19H20F3IN2O5S; GTPL7942; Refametinib (BAY86-9766); CHEMBL1236682; DTXSID40238961; BDBM520650; 923032-38-6; AOB87134; EX-A2481; 2254AH; MFCD18633256; NSC800864; s1089; ZINC39187987; AKOS025401896; BAY86-9766; CCG-270103; CS-1818; DB06309; NSC-800864; BAY 86-9766;RDEA119; BAY-86-9766; BAY-8697661; NCGC00188380-01; NCGC00188380-02; NCGC00188380-03; AC-26962; AS-16994; Cyclopropanesulfonamide, N-(3,4-difluoro-2-((2-fluoro-4-iodophenyl)amino)-6-methoxyphenyl)-1-((2S)-2,3-dihydroxypropyl)-; HY-14691; SW218136-2; J3.661.482J; F51934; US11147816, Refametinib (RDEA119, Bay; Q27088526; BAY 869766;BAY 86-97661;RDEA-119;RDEA119; (S)-N-(3,4-difluoro-2-(2-fluoro-4-iodophenylamino)-6-methoxyphenyl)-1-(2,3-dihydroxypropyl)cyclopropane-1-sulfonamide; 923032-36-4; N-{3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]-6-methoxyphenyl}-1-[(2S)-2,3-dihydroxypropyl]cyclopropanesulfonamide; RDEA-119 S enantiomer; ; ; BAY-86-9766 S enantiomer; ; ; N-[3,4-Difluoro-2-(2-fluoro-4-iodoanilino)-6-methoxyphenyl]-1-[(2S)-2,3-dihydroxypropyl]cyclopropane-1-sulfonamide; VRA
• Indication:
  In total 1 Indication(s)
  Thrombosis [ICD-11: DB61-GB90]; Phase 3; [1]
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
  Melanoma [ICD-11: 2C30]; [2]
• Target: PI3-kinase beta (PIK3CB); PK3CB_HUMAN; [2]
• Formula: 9
• IsoSMILES: COC1=CC(=C(C(=C1NS(=O)(=O)C2(CC2)C[C@@H](CO)O)NC3=C(C=C(C=C3)I)F)F)F
• InChI: InChI=1S/C19H20F3IN2O5S/c1-30-15-7-13(21)16(22)18(24-14-3-2-10(23)6-12(14)20)17(15)25-31(28,29)19(4-5-19)8-11(27)9-26/h2-3,6-7,11,24-27H,4-5,8-9H2,1H3/t11-/m0/s1
• InChIKey: RDSACQWTXKSHJT-NSHDSACASA-N
• PubChem CID: 44182295
• TTD Drug ID: D0D0QA
• VARIDT ID: DR1879
• DrugBank ID: DB06309

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

Colorectal cancer [ICD-11: 2B91]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [3]

• Molecule Alteration: Missense mutation; p.V600E (c.1799T>A)
• Sensitive Disease: Colorectal cancer [ICD-11: 2B91.1]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: MDA-MB-231 cells; Breast; Homo sapiens (Human); CVCL_0062
• In Vitro Model: A375 cells; Skin; Homo sapiens (Human); CVCL_0132
• In Vitro Model: HT-29 cells; Colon; Homo sapiens (Human); CVCL_0320
• In Vitro Model: A431 cells; Skin; Homo sapiens (Human); CVCL_0037
• In Vitro Model: COLO205 cells; Colon; Homo sapiens (Human); CVCL_F402
• In Vitro Model: BxPc3 cells; Pancreas; Homo sapiens (Human); CVCL_0186
• In Vitro Model: SkMEL28 cells; Skin; Homo sapiens (Human); CVCL_0526
• In Vivo Model: Female athymic nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Biochemical kinase assays
• Experiment for Drug Resistance: CellTiter 96 Aqueous One assay
• Mechanism Description: The missense mutation p.V600E (c.1799T>A) in gene BRAF cause the sensitivity of Refametinib by unusual activation of pro-survival pathway

Lung cancer [ICD-11: 2C25]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: MAPK/ERK kinase 1 (MEK1) [1]

• Molecule Alteration: Missense mutation; p.Q56P (c.167A>C)
• Sensitive Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vitro Model: AGS cells; Gastric; Homo sapiens (Human); CVCL_0139
• In Vitro Model: NCI-N87 cells; Gastric; Homo sapiens (Human); CVCL_1603
• In Vitro Model: NCI-H508 cells; Colon; Homo sapiens (Human); CVCL_1564
• In Vitro Model: SW48 cells; Colon; Homo sapiens (Human); CVCL_1724
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• In Vitro Model: NCI-H460 cells; Lung; Homo sapiens (Human); CVCL_0459
• In Vitro Model: NCI-H1650 cells; Lung; Homo sapiens (Human); CVCL_1483
• In Vitro Model: SW1573 cells; Lung; Homo sapiens (Human); CVCL_1720
• In Vitro Model: SNU-C1 cells; Peritoneum; Homo sapiens (Human); CVCL_1708
• In Vitro Model: OCUM-1 cells; Pleural effusion; Homo sapiens (Human); CVCL_3084
• In Vitro Model: NCI-H226 cells; Pleural effusion; Homo sapiens (Human); CVCL_1544
• In Vitro Model: NCI-H196 cells; Pleural effusion; Homo sapiens (Human); CVCL_1509
• In Vitro Model: NCI-H1437 cells; Pleural effusion; Homo sapiens (Human); CVCL_1472
• In Vitro Model: NCI-H1355 cells; Pleural effusion; Homo sapiens (Human); CVCL_1464
• In Vitro Model: MKN7 cells; Lymph node; Homo sapiens (Human); CVCL_1417
• In Vitro Model: NCI-H1299 cells; Lymph node; Homo sapiens (Human); CVCL_0060
• In Vitro Model: HCC366 cells; Lung; Homo sapiens (Human); CVCL_2059
• In Vitro Model: NCI-H2126 cells; Pleural effusion; Homo sapiens (Human); CVCL_1532
• In Vivo Model: Female nu/nu mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CellTiter-Glo assay

Melanoma [ICD-11: 2C30]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [2]

• Molecule Alteration: Missense mutation; p.V600X (c.1798_1799)
• Resistant Disease: Melanoma [ICD-11: 2C30.0]
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: The missense mutation p.V600X (c.1798_1799) in gene BRAF cause the resistance of Refametinib by aberration of the drug's therapeutic target

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [3]

• Molecule Alteration: Missense mutation; p.V600E (c.1799T>A)
• Sensitive Disease: Melanoma [ICD-11: 2C30.0]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: MDA-MB-231 cells; Breast; Homo sapiens (Human); CVCL_0062
• In Vitro Model: A375 cells; Skin; Homo sapiens (Human); CVCL_0132
• In Vitro Model: HT-29 cells; Colon; Homo sapiens (Human); CVCL_0320
• In Vitro Model: A431 cells; Skin; Homo sapiens (Human); CVCL_0037
• In Vitro Model: COLO205 cells; Colon; Homo sapiens (Human); CVCL_F402
• In Vitro Model: BxPc3 cells; Pancreas; Homo sapiens (Human); CVCL_0186
• In Vitro Model: SkMEL28 cells; Skin; Homo sapiens (Human); CVCL_0526
• In Vivo Model: Female athymic nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Biochemical kinase assays
• Experiment for Drug Resistance: CellTiter 96 Aqueous One assay
• Mechanism Description: The missense mutation p.V600E (c.1799T>A) in gene BRAF cause the sensitivity of Refametinib by unusual activation of pro-survival pathway

Uveal melanoma [ICD-11: 2D0Y]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Guanine nucleotide-binding protein alpha-q (GNAQ) [2]

• Molecule Alteration: Missense mutation; p.Q209L (c.626A>T)
• Sensitive Disease: Uveal melanoma [ICD-11: 2D0Y.0]
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: The missense mutation p.Q209L (c.626A>T) in gene GNAQ cause the sensitivity of Refametinib by aberration of the drug's therapeutic target

References

• Ref 1: Identification of an "Exceptional Responder" Cell Line to MEK1 Inhibition: Clinical Implications for MEK-Targeted TherapyMol Cancer Res. 2016 Feb;14(2):207-15. doi: 10.1158/1541-7786.MCR-15-0321. Epub 2015 Nov 18.
• Ref 2: Multicenter phase I trial of the mitogen-activated protein kinase 1/2 inhibitor BAY 86-9766 in patients with advanced cancerClin Cancer Res. 2013 Mar 1;19(5):1232-43. doi: 10.1158/1078-0432.CCR-12-3529. Epub 2013 Feb 22.
• Ref 3: RDEA119/BAY 869766: a potent, selective, allosteric inhibitor of MEK1/2 for the treatment of cancerCancer Res. 2009 Sep 1;69(17):6839-47. doi: 10.1158/0008-5472.CAN-09-0679. Epub 2009 Aug 25.