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], [3]
Renal cell carcinoma 2C90 Phase 2 [2], [3]
Squamous head and neck cell carcinom 2D60.0 Phase 2 [2], [3]
Solid tumour/cancer 2A00-2F9Z Phase 1 [2], [3]
Therapeutic Class
Anticancer Agents
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 3 Molecular Weight (mw) 632.7
Topological Polar Surface Area (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

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 [4]
Vascular endothelial growth factor receptor 2 (KDR) TTUTJGQ VGFR2_HUMAN Modulator [4]
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 Clinical pipeline report, company report or official report of Exelixis (2011).
4 Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
5 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
6 Clinical pipeline report, company report or official report of Exelixis (2011).
7 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
8 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2021
9 Antitumor Activity of Amivantamab (JNJ-61186372), an EGFR-MET Bispecific Antibody, in Diverse Models of EGFR Exon 20 Insertion-Driven NSCLC. Cancer Discov. 2020 Aug;10(8):1194-1209.
10 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. (Target id: 1815).
11 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
12 Beperminogene perplasmid for the treatment of critical limb ischemia. Expert Rev Cardiovasc Ther. 2014 Oct;12(10):1145-56.
13 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: 7948).
14 Preclinical overview of sorafenib, a multikinase inhibitor that targets both Raf and VEGF and PDGF receptor tyrosine kinase signaling.Mol Cancer Ther.2008 Oct;7(10):3129-40.
15 Anthranilic acid amides: a novel class of antiangiogenic VEGF receptor kinase inhibitors. J Med Chem. 2002 Dec 19;45(26):5687-93.
16 2006 drug approvals: finding the niche. Nat Rev Drug Discov. 2007 Feb;6(2):99-101.
17 Nat Rev Drug Discov. 2013 Feb;12(2):87-90.
18 A comparison of physicochemical property profiles of marketed oral drugs and orally bioavailable anti-cancer protein kinase inhibitors in clinical development. Curr Top Med Chem. 2007;7(14):1408-22.
19 Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
20 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services
21 Emerging drugs for ovarian cancer. Expert Opin Emerg Drugs. 2008 Sep;13(3):523-36.