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Details

Stereochemistry ACHIRAL
Molecular Formula C22H22N4O4S
Molecular Weight 438.5014
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of S-49076

SMILES

c1cc2c(cc1CN3C(=O)CSC3=O)/C(=C(\[H])/c4cc(c[nH]4)CN5CCOCC5)/C(=N2)O

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-

HIDE SMILES / InChI

Molecular Formula C22H22N4O4S
Molecular Weight 438.5014
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 1
Optical Activity NONE

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
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]
7.0 nM [IC50]
1.0 nM [IC50]
18.0 nM [IC50]
17.0 nM [IC50]
15.0 nM [IC50]
PubMed

PubMed

TitleDatePubMed
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 Sat Jun 26 16:12:41 UTC 2021
Edited
by admin
on Sat Jun 26 16:12:41 UTC 2021
Record UNII
65ZUU7MATU
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
S-49076
Code English
2,4-THIAZOLIDINEDIONE, 3-((2,3-DIHYDRO-3-((4-(4-MORPHOLINYLMETHYL)-1H-PYRROL-2-YL)METHYLENE)-2-OXO-1H-INDOL-5-YL)METHYL)-
Systematic Name English
S 49076
Code English
3-((3-((4-((4-MORPHOLINYL)METHYL)-1H-PYRROL-2-YL)METHYLENE)-2-OXO-2,3-DIHYDRO-1H-INDOL-5-YL)METHYL)-1,3-THIAZOLIDINE-2,4-DIONE
Systematic Name English
S-49076(FREE BASE)
Common Name English
Code System Code Type Description
MANUFACTURER PRODUCT INFORMATION
S-49076(FREE BASE)
Created by admin on Sat Jun 26 16:12:41 UTC 2021 , Edited by admin on Sat Jun 26 16:12:41 UTC 2021
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.
CAS
1265965-22-7
Created by admin on Sat Jun 26 16:12:41 UTC 2021 , Edited by admin on Sat Jun 26 16:12:41 UTC 2021
PRIMARY
FDA UNII
65ZUU7MATU
Created by admin on Sat Jun 26 16:12:41 UTC 2021 , Edited by admin on Sat Jun 26 16:12:41 UTC 2021
PRIMARY
PUBCHEM
49870909
Created by admin on Sat Jun 26 16:12:41 UTC 2021 , Edited by admin on Sat Jun 26 16:12:41 UTC 2021
PRIMARY
Related Record Type Details
SALT/SOLVATE -> PARENT
TARGET -> INHIBITOR
COMPETITIVE INHIBITOR
IC50
Related Record Type Details
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.