Details
Stereochemistry | ACHIRAL |
Molecular Formula | C31H27F2N5O3S2 |
Molecular Weight | 619.705 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
COCCNCC1=CC=C(N=C1)C2=CC3=C(S2)C(OC4=C(F)C=C(NC(=S)NC(=O)CC5=CC=C(F)C=C5)C=C4)=CC=N3
InChI
InChIKey=YRCHYHRCBXNYNU-UHFFFAOYSA-N
InChI=1S/C31H27F2N5O3S2/c1-40-13-12-34-17-20-4-8-24(36-18-20)28-16-25-30(43-28)27(10-11-35-25)41-26-9-7-22(15-23(26)33)37-31(42)38-29(39)14-19-2-5-21(32)6-3-19/h2-11,15-16,18,34H,12-14,17H2,1H3,(H2,37,38,39,42)
Molecular Formula | C31H27F2N5O3S2 |
Molecular Weight | 619.705 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/?term=28024693Curator's Comment: Description was created using several sources including:
http://www.generon.co.uk/amine-oxides-1830/mgcd-265--182002623.html | https://clinicaltrials.gov/ct2/show/NCT02544633
Sources: https://www.ncbi.nlm.nih.gov/pubmed/?term=28024693
Curator's Comment: Description was created using several sources including:
http://www.generon.co.uk/amine-oxides-1830/mgcd-265--182002623.html | https://clinicaltrials.gov/ct2/show/NCT02544633
Glesatinib (MGCD265) is an orally bioavailable, small-molecule, multitargeted tyrosine kinase inhibitor with potential antineoplastic activity. Glesatinib binds to and inhibits the phosphorylation of several receptor tyrosine kinases (RTKs), including the c-Met receptor (hepatocyte growth factor receptor); the Tek/Tie-2 receptor; vascular endothelial growth factor receptor (VEGFR) types 1, 2, and 3; and the macrophage-stimulating 1 receptor (MST1R or RON). Inhibition of these RTKs and their downstream signaling pathways may result in the inhibition of tumor angiogenesis and tumor cell proliferation in tumors overexpressing these RTKs. Studies in a gastric cancer xenograft model revealed that, in addition to the typically reported cellular activities, glesatinib in combination with erlotinib disrupted the glycolysis pathway, suggesting a novel mechanism of action for this drug. Glesatinib has been studied in a variety of advanced solid tumors including NSCLC, as a monotherapy and in combination with either docetaxel or erlotinib. In an ongoing phase 1 study in patients with MET positive or AXL-rearranged advanced solid tumors, glesatinib demonstrated preliminary single-agent activity, with all three patients with MET dysregulated NSCLC (two with METex14 alterations and one with increased GCN) showing significant tumor regression at the first assessment. A phase 2 study is currently recruiting patients with MET-dysregulated (mutated or amplified) advanced or metastatic NSCLC.
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: P08581 Gene ID: 4233.0 Gene Symbol: MET Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/?term=28024693 |
1.0 nM [IC50] | ||
Target ID: CHEMBL279 Sources: https://www.ncbi.nlm.nih.gov/pubmed/?term=28024693 |
3.0 nM [IC50] | ||
Target ID: CHEMBL1868 Sources: https://www.ncbi.nlm.nih.gov/pubmed/?term=28024693 |
3.0 nM [IC50] | ||
Target ID: CHEMBL1955 Sources: https://www.ncbi.nlm.nih.gov/pubmed/?term=28024693 |
4.0 nM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Unknown Approved UseUnknown |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
60.49 ng/mL CLINICAL TRIAL https://clinicaltrials.gov/study/NCT02544633 |
1050 mg 2 times / day multiple, oral dose: 1050 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
GLESATINIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
328.1 ng/mL CLINICAL TRIAL https://clinicaltrials.gov/study/NCT02544633 |
1050 mg 2 times / day multiple, oral dose: 1050 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
GLESATINIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
29.8 ng/mL |
24 mg/m² single, oral dose: 24 mg/m² route of administration: Oral experiment type: SINGLE co-administered: |
GLESATINIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
185.5 ng × h/mL CLINICAL TRIAL https://clinicaltrials.gov/study/NCT02544633 |
1050 mg 2 times / day multiple, oral dose: 1050 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
GLESATINIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
1837 ng × h/mL CLINICAL TRIAL https://clinicaltrials.gov/study/NCT02544633 |
1050 mg 2 times / day multiple, oral dose: 1050 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
GLESATINIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
816 ng × h/mL |
24 mg/m² single, oral dose: 24 mg/m² route of administration: Oral experiment type: SINGLE co-administered: |
GLESATINIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
22.4 h |
24 mg/m² single, oral dose: 24 mg/m² route of administration: Oral experiment type: SINGLE co-administered: |
GLESATINIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
Sample Use Guides
MGCD265 (glesatinib) was given orally from 24 mg/m2 daily to 235 mg/m2 twice daily uninterrupted to patients with advanced solid malignancy until disease progression
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/?term=28024693
In MKN45 cells the IC50 value of glesatinib was 20 nM
Substance Class |
Chemical
Created
by
admin
on
Edited
Mon Mar 31 23:20:52 GMT 2025
by
admin
on
Mon Mar 31 23:20:52 GMT 2025
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Record UNII |
7Q29OXD98N
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Validated (UNII)
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NCI_THESAURUS |
C129825
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NCI_THESAURUS |
C1967
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1044577-56-1
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10217
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DB06302
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C77876
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7Q29OXD98N
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Glesatinib
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DE-141
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1072115-99-1
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25181472
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936694-12-1
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CHEMBL254760
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DTXSID601337113
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100000175671
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Related Record | Type | Details | ||
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TARGET -> INHIBITOR |
COMPETITIVE INHIBITOR
IC50
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TARGET -> INHIBITOR |
COMPETITIVE INHIBITOR
IC50
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TARGET -> INHIBITOR |
COMPETITIVE INHIBITOR
IC50
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TARGET -> INHIBITOR | |||
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SALT/SOLVATE -> PARENT | |||
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TARGET -> INHIBITOR |
COMPETITIVE INHIBITOR
IC50
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TARGET -> INHIBITOR |
COMPETITIVE INHIBITOR
IC50
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ACTIVE MOIETY |