Details
| Stereochemistry | ACHIRAL |
| Molecular Formula | C22H22N4O4S |
| Molecular Weight | 438.499 |
| Optical Activity | NONE |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 1 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
O=C1CSC(=O)N1CC2=CC3=C(NC(=O)\C3=C/C4=CC(CN5CCOCC5)=CN4)C=C2
InChI
InChIKey=AREYWCZYVPSHGS-NVMNQCDNSA-N
InChI=1S/C22H22N4O4S/c27-20-13-31-22(29)26(20)12-14-1-2-19-17(8-14)18(21(28)24-19)9-16-7-15(10-23-16)11-25-3-5-30-6-4-25/h1-2,7-10,23H,3-6,11-13H2,(H,24,28)/b18-9-
| Molecular Formula | C22H22N4O4S |
| Molecular Weight | 438.499 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 1 |
| Optical Activity | NONE |
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
Target ID: P08581 Gene ID: 4233.0 Gene Symbol: MET Target Organism: Homo sapiens (Human) |
1.0 nM [IC50] | ||
Target ID: P30530 Gene ID: 558.0 Gene Symbol: AXL Target Organism: Homo sapiens (Human) |
7.0 nM [IC50] | ||
Target ID: Q12866 Gene ID: 10461.0 Gene Symbol: MERTK Target Organism: Homo sapiens (Human) |
2.0 nM [IC50] | ||
Target ID: CHEMBL2095217 |
|||
Target ID: CHEMBL4895 |
7.0 nM [IC50] | ||
| 1.0 nM [IC50] | |||
| 18.0 nM [IC50] | |||
Target ID: CHEMBL4142 |
17.0 nM [IC50] | ||
Target ID: CHEMBL2742 |
15.0 nM [IC50] |
PubMed
| Title | Date | PubMed |
|---|---|---|
| S49076 is a novel kinase inhibitor of MET, AXL, and FGFR with strong preclinical activity alone and in association with bevacizumab. | 2013 Sep |
|
| First-in-human phase I study of oral S49076, a unique MET/AXL/FGFR inhibitor, in advanced solid tumours. | 2017 Aug |
|
| The MET/AXL/FGFR Inhibitor S49076 Impairs Aurora B Activity and Improves the Antitumor Efficacy of Radiotherapy. | 2017 Oct |
| Substance Class |
Chemical
Created
by
admin
on
Edited
Sat Dec 16 11:43:35 GMT 2023
by
admin
on
Sat Dec 16 11:43:35 GMT 2023
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| Record UNII |
65ZUU7MATU
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| Record Status |
Validated (UNII)
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| Record Version |
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S-49076(FREE BASE)
Created by
admin on Sat Dec 16 11:43:35 GMT 2023 , Edited by admin on Sat Dec 16 11:43:35 GMT 2023
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PRIMARY | MedKoo CAT NO: 206484, CAS NO: 1265965-22-7Description: S49076 is a novel, potent inhibitor of MET, AXL/MER, and FGFR1/2/3. S49076 potently blocked cellular phosphorylation of MET, AXL, and FGFRs and inhibited downstream signaling in vitro and in vivo. In cell models, S49076 inhibited the proliferation of MET- and FGFR2-dependent gastric cancer cells, blocked MET-driven migration of lung carcinoma cells, and inhibited colony formation of hepatocarcinoma cells expressing FGFR1/2 and AXL. In tumor xenograft models, a good pharmacokinetic/pharmacodynamic relationship for MET and FGFR2 inhibition following oral administration of S49076 was established and correlated well with impact on tumor growth. MET, AXL, and the FGFRs have all been implicated in resistance to VEGF/VEGFR inhibitors such as bevacizumab. A phase I study with S-49076 is currently underway in patients with advanced solid tumors. | ||
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1265965-22-7
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300000042471
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49870909
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| Related Record | Type | Details | ||
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SALT/SOLVATE -> PARENT | |||
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TARGET -> INHIBITOR |
COMPETITIVE INHIBITOR
IC50
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| Related Record | Type | Details | ||
|---|---|---|---|---|
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ACTIVE MOIETY |
Three pts were respectively treated at the dose levels 400 mg and 500 mg and 6 patients at 600 mg (due to 1 DLT observed, G3 asymptomatic ejection fraction decrease). This dose level was considered as the RP2D. The reported adverse events (AE) related to S49076 were mainly of G1 or G2 (2 AE G3). No grade 5 S49076 and/or BEV related AE has been observed. Best responses for the 12 evaluable pts were: 4 partial responses (PR) confirmed and 2 unconfirmed, 5 stable disease (SD) including 2 SD 3 months, and 1 progressive disease. Similar S49076 PK profile in combination to BEV has been observed in the first-in-human study where S49076 was used in monotherapy. PD results showed high and moderate MET amplification assessed by FISH in 2 pts which were not predictive of clinical response. No expression of MET and AXL were observed by immunohistochemistry (IHC) in any of the pts.
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