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Details

Stereochemistry ACHIRAL
Molecular Formula C18H13N7S
Molecular Weight 359.408
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of SGX-523

SMILES

CN1C=C(C=N1)C2=NN3C(SC4=CC5=CC=CN=C5C=C4)=NN=C3C=C2

InChI

InChIKey=BCZUAADEACICHN-UHFFFAOYSA-N
InChI=1S/C18H13N7S/c1-24-11-13(10-20-24)16-6-7-17-21-22-18(25(17)23-16)26-14-4-5-15-12(9-14)3-2-8-19-15/h2-11H,1H3

HIDE SMILES / InChI

Molecular Formula C18H13N7S
Molecular Weight 359.408
Charge 0
Count
MOL RATIO 1 MOL RATIO (average)
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description

SGX523 is a selective, ATP-competitive inhibitor of the MET receptor tyrosine kinase. SGX523 was able to inhibit HGF-induced cell migration and cell scatter. SGX523 inhibition of MET in vivo was associated with the dose-dependent inhibition of growth of tumor xenografts derived from human glioblastoma and lung and gastric cancers. The clinical development of SGX523, however, was discontinued at Phase I due to renal toxicity manifested by an early rise of serum blood urea nitrogen and creatinine.

CNS Activity

Originator

Approval Year

Targets

Primary TargetPharmacologyConditionPotency
2.7 nM [Ki]

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

AUC

ValueDoseCo-administeredAnalytePopulation
10702 ng × h/mL
5 mg/kg single, oral
SGX-523 unknown
Rattus norvegicus

T1/2

ValueDoseCo-administeredAnalytePopulation
3.1 h
5 mg/kg single, oral
SGX-523 unknown
Rattus norvegicus

PubMed

Sample Use Guides

In Vivo Use Guide
In a phase I clinical trials SGX523 was administered on an intermittent schedule at a starting dose of 60 mg PO BID for 14 days followed by 7 days of rest. The second protocol explored a continuous 28-day dosing schedule with SGX523 administered at a starting dose of 20 mg PO BID for 28 days without rest.
Route of Administration: Oral
In Vitro Use Guide
To investigate cell migration, A549 cells were plated in 12-well plates (6 × 104 per well) and incubated to confluence. A channel was introduced into the monolayers by scratching with a pipette tip. Various dilutions of the compound were added in starve medium in the presence and absence of HGF (90 ng/mL). Twenty-four hours later, wells were checked for cell migration. Cells were stained and visualized. SGX523 was active in prevention cells migration at concentrations above 50 nM
Substance Class Chemical
Record UNII
WH8SQN09KJ
Record Status Validated (UNII)
Record Version