Details
Stereochemistry | ACHIRAL |
Molecular Formula | C26H21F3N4O4 |
Molecular Weight | 510.4645 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
FC1=CC=C(NC(=O)C2(CC2)C(=O)NC3=C(F)C=C(OC4=CC=NC(NC(=O)C5CC5)=C4)C(F)=C3)C=C1
InChI
InChIKey=GNNDEPIMDAZHRQ-UHFFFAOYSA-N
InChI=1S/C26H21F3N4O4/c27-15-3-5-16(6-4-15)31-24(35)26(8-9-26)25(36)32-20-12-19(29)21(13-18(20)28)37-17-7-10-30-22(11-17)33-23(34)14-1-2-14/h3-7,10-14H,1-2,8-9H2,(H,31,35)(H,32,36)(H,30,33,34)
Altiratinib, a novel c-MET/TIE-2/VEGFR inhibitor, was able to effectively reduce tumor burden in vivo and block c-MET signaling, cell growth and migration. Altiratinib inhibits not only mechanisms of tumor initiation and progression, but also drug resistance mechanisms in the tumor and microenvironment. Altiratinib durably inhibits MET, both wild-type and mutated forms, in vitro and in vivo. Altiratinib exhibits properties amenable to oral administration and exhibits substantial blood-brain barrier penetration, an attribute of significance for eventual treatment of brain cancers and brain metastases. It is currently in Phase 1 clinical development for the treatment of solid tumors.
CNS Activity
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL3717 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26285778 |
2.7 nM [IC50] | ||
Target ID: CHEMBL2815 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26285778 |
0.85 nM [IC50] | ||
Target ID: CHEMBL5608 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26285778 |
0.83 nM [IC50] | ||
Target ID: CHEMBL4898 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26285778 |
4.6 nM [IC50] | ||
Target ID: CHEMBL4128 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26285778 |
8.0 nM [IC50] | ||
Target ID: CHEMBL279 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26285778 |
9.2 nM [IC50] | ||
Target ID: CHEMBL1974 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26285778 |
9.3 nM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
PubMed
Title | Date | PubMed |
---|---|---|
Altiratinib Inhibits Tumor Growth, Invasion, Angiogenesis, and Microenvironment-Mediated Drug Resistance via Balanced Inhibition of MET, TIE2, and VEGFR2. | 2015 Sep |
|
Novel MET/TIE2/VEGFR2 inhibitor altiratinib inhibits tumor growth and invasiveness in bevacizumab-resistant glioblastoma mouse models. | 2016 Sep |
Patents
Sample Use Guides
In escalating dose (starting dose 15 mg) twice daily every 12 hours for a 28-day cycle
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/26285778
EBC-1 (NSCLC) and MKN-45 (gastric cancer) human cancer cell lines genomically amplify and overexpress MET with subsequent
ligand-independent MET activation. Altiratinib inhibited MET phosphorylation with IC50 values of 0.85 nmol/L and 2.2 nM/L, respectively. In the U-87 glioblastoma cell line, MET and HGF are both expressed. Altiratinib blocked autocrine activation of MET phosphorylation in these cells (IC50 of 6.2 nM/L).
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Classification Tree | Code System | Code | ||
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FDA ORPHAN DRUG |
441714
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NCI_THESAURUS |
C1967
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NCI_THESAURUS |
C129825
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NCI_THESAURUS |
C1742
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1345847-93-9
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CHEMBL3545365
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C118290
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300000034087
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BC-79
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T678746713
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54576299
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10100
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ACTIVE MOIETY