Details of the Drug

General Information of Drug (ID: DMHJTR2)

Drug Name
XL880
Synonyms GSK 089; GSK 1363089; GSK1363089; XL 880; GSK1363089, GSK089, foretinib, EXEL-2880, XL880; 88Z; MET inhibitors
Indication
Disease Entry ICD 11 Status REF
Breast cancer 2C60-2C65 Phase 2 [1]
Gastric adenocarcinoma 2B72 Phase 2 [2]
Renal cell carcinoma 2C90 Phase 2 [2]
Squamous head and neck cell carcinom 2D60.0 Phase 2 [2]
Solid tumour/cancer 2A00-2F9Z Phase 1 [2]
Therapeutic Class
Anticancer Agents
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 3 Molecular Weight (mw) 632.7
Logarithm of the Partition Coefficient (xlogp) 5.5
Rotatable Bond Count (rotbonds) 12
Hydrogen Bond Donor Count (hbonddonor) 2
Hydrogen Bond Acceptor Count (hbondacc) 10
Chemical Identifiers
Formula
C34H34F2N4O6
IUPAC Name
1-N'-[3-fluoro-4-[6-methoxy-7-(3-morpholin-4-ylpropoxy)quinolin-4-yl]oxyphenyl]-1-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide
Canonical SMILES
COC1=CC2=C(C=CN=C2C=C1OCCCN3CCOCC3)OC4=C(C=C(C=C4)NC(=O)C5(CC5)C(=O)NC6=CC=C(C=C6)F)F
InChI
InChI=1S/C34H34F2N4O6/c1-43-30-20-25-27(21-31(30)45-16-2-13-40-14-17-44-18-15-40)37-12-9-28(25)46-29-8-7-24(19-26(29)36)39-33(42)34(10-11-34)32(41)38-23-5-3-22(35)4-6-23/h3-9,12,19-21H,2,10-11,13-18H2,1H3,(H,38,41)(H,39,42)
InChIKey
CXQHYVUVSFXTMY-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
42642645
ChEBI ID
CHEMBL91418
CAS Number
849217-64-7
UNII
81FH7VK1C4
DrugBank ID
DB12307
TTD ID
D0D1GF
Drug-Molecule Activity Atlas (DMA)NEW Click to Jump to the Detailed DMA Information of This Drug
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Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Proto-oncogene c-Met (MET) TTNDSF4 MET_HUMAN Modulator [3]
Vascular endothelial growth factor receptor 2 (KDR) TTUTJGQ VGFR2_HUMAN Modulator [3]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
Hepatocyte growth factor receptor (MET) OT7K55MU MET_HUMAN Post-Translational Modifications [4]
Proto-oncogene tyrosine-protein kinase Src (SRC) OTETYX40 SRC_HUMAN Post-Translational Modifications [4]
Tyrosine-protein kinase receptor UFO (AXL) OTKA2SUX UFO_HUMAN Gene/Protein Processing [5]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Breast cancer
ICD Disease Classification 2C60-2C65
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Vascular endothelial growth factor receptor 2 (KDR) DTT KDR 1.98E-01 0.11 0.2
Proto-oncogene c-Met (MET) DTT MET 1.08E-03 -0.24 -0.4
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

References

1 ClinicalTrials.gov (NCT01147484) A Study of Foretinib in Patients With Recurrent/Metastatic Breast Cancer (IND197). U.S. National Institutes of Health.
2 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 5679).
3 Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
4 LRIG1 modulates cancer cell sensitivity to Smac mimetics by regulating TNF expression and receptor tyrosine kinase signaling. Cancer Res. 2012 Mar 1;72(5):1229-38. doi: 10.1158/0008-5472.CAN-11-2428. Epub 2012 Jan 12.
5 Activation of the AXL kinase causes resistance to EGFR-targeted therapy in lung cancer. Nat Genet. 2012 Jul 1;44(8):852-60. doi: 10.1038/ng.2330.