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
CHEBI:91418
CAS Number
849217-64-7
DrugBank ID
DB12307
TTD ID
D0D1GF
Combinatorial Drugs (CBD) Click to Jump to the Detailed CBD Information of This Drug
Repurposed Drugs (RPD) Click to Jump to the Detailed RPD Information of This Drug

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.