Drug Information

Drug (ID: DG01519) and It's Reported Resistant Information

• Name: RO4987655
• Synonyms: RO4987655; 874101-00-5; RO-4987655; CH4987655; CH-4987655; UNII-I3733P75ML; 3,4-Difluoro-2-[(2-Fluoro-4-Iodophenyl)amino]-N-(2-Hydroxyethoxy)-5-[(3-Oxo-1,2-Oxazinan-2-Yl)methyl]benzamide; 3,4-difluoro-2-(2-fluoro-4-iodophenylamino)-N-(2-hydroxyethoxy)-5-((3-oxomorpholino)methyl)benzamide; CHEMBL1614766; I3733P75ML; RO 4987655; 3,4-Difluoro-2-((2-fluoro-4-iodophenyl)amino)-N-(2-hydroxyethoxy)-5-((3-oxo-1,2-oxazinan-2-yl)methyl)benzamide; C20H19F3IN3O5; 3,4-Difluoro-2-(2-fluoro-4-iodo-anilino)-N-(2-hydroxyethoxy)-5-[(3-oxooxazinan-2-yl)methyl]benzamide; 3orn; GTPL9910; SCHEMBL1562083; SYN1188; BCP12182; EX-A2312; 4014AH; BDBM50338038; NSC762521; NSC800870; RG7167; ZINC43103796; AKOS005266648; DB12933; NSC-762521; NSC-800870; SB16732; r-7167; compound 24 [PMID: 21316218]; NCGC00378595-03; AS-16322; HY-14719; DS-016573; B3261; US8575391, 334; RO4987655; CH-4987655; Q27280303; 3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-N-(2-hydroxy-ethoxy)-5-(3-oxo-[1,2]oxazinan-2-ylmethyl)-benzamide; 3,4-Difluoro-2-(2-fluoro-4-iodoanilino)-N-(2-hydroxyethoxy)-5-[(3-oxo-2-oxazinanyl)methyl]benzamide; 3,4-difluoro-2-(2-fluoro-4-iodoanilino)-N-(2-hydroxyethoxy)-5-[(3-oxooxazinan-2-yl)methyl]benzamide; 3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]-N-(2-hydroxyethoxy)-5-[(3-oxooxazinan-2-yl)methyl]benzamide; 3OR; Benzamide, 3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]-N-(2-hydroxyethoxy)-5-[(tetrahydro-3-oxo-2H-1,2-oxazin-2-yl)methyl]-
• Formula: 8
• IsoSMILES: C1CC(=O)N(OC1)CC2=CC(=C(C(=C2F)F)NC3=C(C=C(C=C3)I)F)C(=O)NOCCO
• InChI: InChI=1S/C20H19F3IN3O5/c21-14-9-12(24)3-4-15(14)25-19-13(20(30)26-31-7-5-28)8-11(17(22)18(19)23)10-27-16(29)2-1-6-32-27/h3-4,8-9,25,28H,1-2,5-7,10H2,(H,26,30)
• InChIKey: FIMYFEGKMOCQKT-UHFFFAOYSA-N
• PubChem CID: 11548630
• DrugBank ID: DB12933

Type(s) of Resistant Mechanism of This Drug

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Their Corresponding Diseases

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

Melanoma [ICD-11: 2C30]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [1]

• Sensitive Disease: Melanoma [ICD-11: 2C30.0]
• Molecule Alteration: Missense mutation; p.V600E (c.1799T>A)
• Wild Type Structure: Method: X-ray diffraction; Resolution: 2.55 Å; PDB: 4E26
• Mutant Type Structure: Method: X-ray diffraction; Resolution: 3.20 Å; PDB: 4G9R

RMSD: 1.53; TM score: 0.95765; Amino acid change: V600E

• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vitro Model: NCI-N87 cells; Gastric; Homo sapiens (Human); CVCL_1603
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• In Vitro Model: NCI-H716 cells; Colon; Homo sapiens (Human); CVCL_1581
• In Vitro Model: SNU-16 cells; Gastric; Homo sapiens (Human); CVCL_0076
• In Vitro Model: NCI-H520 cells; Lung; Homo sapiens (Human); CVCL_1566
• In Vitro Model: RT-4 cells; Urinary bladder; Homo sapiens (Human); CVCL_0036
• In Vitro Model: ZR75-1 cells; Breast; Homo sapiens (Human); CVCL_0588
• In Vitro Model: NCI-N87 cells; Gastric; Homo sapiens (Human); CVCL_1603
• In Vitro Model: NCI-H716 cells; Colon; Homo sapiens (Human); CVCL_1581
• In Vitro Model: KATO-3 cells; Gastric; Homo sapiens (Human); CVCL_0371
• In Vitro Model: SNU-16 cells; Gastric; Homo sapiens (Human); CVCL_0076
• In Vitro Model: NCI-H520 cells; Lung; Homo sapiens (Human); CVCL_1566
• In Vitro Model: RT-4 cells; Urinary bladder; Homo sapiens (Human); CVCL_0036
• In Vitro Model: UM-UC-14 cells; Kidney; Homo sapiens (Human); CVCL_2747
• In Vitro Model: SUM-52PE cells; Pleural effusion; Homo sapiens (Human); CVCL_3425
• In Vitro Model: NCI-H1581 cells; Lung; Homo sapiens (Human); CVCL_1479
• In Vitro Model: MFE296 cells; Endometrium; Homo sapiens (Human); CVCL_1406
• In Vitro Model: MFE280 cells; Endometrium; Homo sapiens (Human); CVCL_1405
• In Vitro Model: KMS-11 cells; Pleural effusion; Homo sapiens (Human); CVCL_2989
• In Vitro Model: HSC-39 cells; Ascites; Homo sapiens (Human); CVCL_A385
• In Vitro Model: DMS-114 cells; Lung; Homo sapiens (Human); CVCL_1174
• In Vitro Model: AN3 CA cells; Endometrium; Homo sapiens (Human); CVCL_0028
• In Vitro Model: UM-UC-14 cells; Kidney; Homo sapiens (Human); CVCL_2747
• In Vitro Model: KATO-III cells; Pleural effusion; Homo sapiens (Human); CVCL_0371
• In Vitro Model: AN3 CA cells; Endometrium; Homo sapiens (Human); CVCL_0028
• Experiment for Molecule Alteration: Microarray assay; Western blot analysis
• Experiment for Drug Resistance: CCK-8 assay

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

• Sensitive Disease: Melanoma [ICD-11: 2C30.0]
• Molecule Alteration: Missense mutation; p.V600X (c.1798_1799)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Skin sample; N.A.
• Experiment for Molecule Alteration: IHC assay; Tumor-DNA mutation analysis
• Experiment for Drug Resistance: Pharmacokinetics analysis; Tumor biopsies analysis

References

• Ref 1: ERK Signal Suppression and Sensitivity to CH5183284/Debio 1347, a Selective FGFR InhibitorMol Cancer Ther. 2015 Dec;14(12):2831-9. doi: 10.1158/1535-7163.MCT-15-0497. Epub 2015 Oct 5.
• Ref 2: Phase I expansion and pharmacodynamic study of the oral MEK inhibitor RO4987655 (CH4987655) in selected patients with advanced cancer with RAS-RAF mutationsClin Cancer Res. 2014 Aug 15;20(16):4251-61. doi: 10.1158/1078-0432.CCR-14-0341. Epub 2014 Jun 19.