S-49076

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=CC=C3NC(=O)\C(=C/C4=CC(CN5CCOCC5)=CN4)C3=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-

HIDE SMILES / InChI

Molecular Formula	C22H22N4O4S
Molecular Weight	438.499
Charge	0
Count	MOL RATIO 1 MOL RATIO (average)

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	1
Optical Activity	NONE

Approval Year

Targets

Targets

Primary Target	Pharmacology	Potency
Hepatocyte growth factor receptor 56	Inhibitor 8,504	1.0 nM [IC50]
Tyrosine-protein kinase receptor UFO 14	Inhibitor 8,504	7.0 nM [IC50]
Tyrosine-protein kinase Mer 3	Inhibitor 8,504	2.0 nM [IC50]
Fibroblast growth factor receptor 6	Inhibitor 8,504
Tyrosine-protein kinase receptor UFO 14	Inhibitor 8,504	7.0 nM [IC50]
Hepatocyte growth factor receptor 56	Inhibitor 8,504	1.0 nM [IC50]
Fibroblast growth factor receptor 1 46	Antagonist 2,849	18.0 nM [IC50]
Fibroblast growth factor receptor 2 25	Antagonist 2,849	17.0 nM [IC50]
Fibroblast growth factor receptor 3 32	Antagonist 2,849	15.0 nM [IC50]

PubMed

PubMed

Show entries

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	23804704
First-in-human phase I study of oral S49076, a unique MET/AXL/FGFR inhibitor, in advanced solid tumours.	2017 Aug	28624695

Showing 1 to 2 of 2 entries

Previous1Next

Substance Class	Chemical
Record UNII	65ZUU7MATU
Record Status	`Validated (UNII)`
Record Version

Show entries

Name

Type

Language

S 49076

Preferred Name

English

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

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

Showing 1 to 5 of 5 entries

Previous1Next

Show entries

Code System

Code

Type

Description

MANUFACTURER PRODUCT INFORMATION

S-49076(FREE BASE)

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

PRIMARY

FDA UNII

65ZUU7MATU

PRIMARY

SMS_ID

300000042471

PRIMARY

PUBCHEM

49870909

PRIMARY

Showing 1 to 5 of 5 entries

Previous1Next

Show entries

Related Record

Type

Details


					ALUH60KSL9

S-49076 HYDROCHLORIDE

SALT/SOLVATE -> PARENT


					8EJE45ZR0I

TYROSINE-PROTEIN KINASE RECEPTOR UFO

TARGET -> INHIBITOR

Interaction Type:

COMPETITIVE INHIBITOR

Qualification:

IC50

Amount:

7 NANOMOLAR (average)

Showing 1 to 2 of 2 entries

Previous1Next

Show entries

Related Record

Type

Details


					65ZUU7MATU

S-49076

ACTIVE MOIETY

Comments:

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.

Showing 1 to 1 of 1 entries

Previous1Next