Home Protein Tyrosine Kinase VEGFR inhibitor SAR131675

연구용

SAR131675 VEGFR3 Inhibitor

제품 번호S2842

SAR131675 is a VEGFR3 inhibitor with IC50/Ki of 23 nM/12 nM in cell-free assays, about 50- and 10-fold more selective for VEGFR3 than VEGFR1/2, little activity against Akt1, CDKs, PLK1, EGFR, IGF-1R, c-Met, Flt2 etc.
SAR131675 VEGFR inhibitor Chemical Structure

화학 구조

분자량: 358.39

바로가기

품질 관리 (Quality Control)

배치: 순도: 99.89%
99.89

화학 정보, 보관 및 안정성 (Chemical Information, Storage & Stability)

분자량 358.39 화학식

C18H22N4O4

 보관 (수령일로부터)
CAS 번호 1433953-83-3 SDF 다운로드 원액 보관

동의어 N/A Smiles CCN1C(=C(C(=O)C2=C1N=C(C=C2)C#CC(C)(COC)O)C(=O)NC)N

용해도 (Solubility)

In vitro
배치:

DMSO : 72 mg/mL (200.89 mM)
(수분으로 오염된 DMSO는 용해도를 감소시킬 수 있습니다. 신선하고 무수 DMSO를 사용하십시오.)

Ethanol : 4 mg/mL

Water : Insoluble

몰농도 계산기

질량 농도 부피 분자량
희석 계산기 분자량 계산기

In vivo
배치:

생체 내 제형 계산기 (투명한 용액)

1단계: 아래 정보 입력 (권장: 실험 중 손실을 고려하여 추가 동물 포함)

mg/kg g μL

2단계: 생체 내 제형 입력 (이것은 계산기일 뿐 제형이 아닙니다. 용해도 섹션에 생체 내 제형이 없는 경우 먼저 당사에 문의하십시오.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

계산 결과:

작업 농도: mg/ml;

DMSO 원액 준비 방법: mg 약물 사전 용해 μL DMSO ( 원액 농도 mg/mL, 농도가 해당 약물 배치의 DMSO 용해도를 초과하는 경우 먼저 당사에 문의하십시오. )

생체 내 제형 준비 방법: 취하다 μL DMSO 원액, 다음 추가μL PEG300, 혼합하고 투명하게 한 다음 추가μL Tween 80, 혼합하고 투명하게 한 다음 추가 μL ddH2O, 혼합하고 투명하게 합니다.

생체 내 제형 준비 방법: 취하다 μL DMSO 원액, 다음 추가 μL 옥수수 기름, 혼합하고 투명하게 합니다.

참고: 1. 다음 용매를 추가하기 전에 액체가 투명한지 확인하십시오.
2. 용매를 순서대로 추가해야 합니다. 다음 용매를 추가하기 전에 이전 추가에서 얻은 용액이 투명한 용액인지 확인해야 합니다. 와동, 초음파 또는 뜨거운 물 중탕과 같은 물리적 방법을 사용하여 용해를 도울 수 있습니다.

작용 메커니즘 (Mechanism of Action)

특징
A potent and selective VEGFR-3–tyrosine kinase inhibitor.
Targets/IC50/Ki
VEGFR3
(Cell-free assay)
23 nM
시험관 내(In vitro)

SAR131675 dose dependently inhibits the proliferation of primary human lymphatic cells, induced by the VEGFR-3 ligands VEGFC and VEGFD, with an IC50 of about 20 nM. This compound dose dependently inhibits rh-VEGFR-3–TK activity with an IC50 of 23 nM. It inhibits VEGR-3–TK activity with a Ki of about 12 nM. It inhibits VEGFR-1–TK activity with an IC50 of > 3 μM and VEGFR-2–TK activity with an IC50 of 235 nM. It inhibits VEGFR-1 autophosphorylation with an IC50 of about 1 μM and VEGFR-2 with an IC50 of about 280 nM. It moderately inhibits VEGFR-2 and has very little effect on VEGFR-1, showing a good selectivity for VEGFR-3. It inhibits VEGFA-induced VEGFR-2 phosphorylation in a dose-dependent manner, with an IC50 of 239 nM. It potently inhibits lymphatic cell survival induced by VEGFC and VEGFD with IC50 of 14 nM and 17 nM, respectively. It inhibits VEGFA-induced survival with an IC50 of 664 nM. It significantly and dose dependently inhibits VEGFC-induced Erk phosphorylation, with an IC50 of about 30 nM.

키나아제 분석
Tyrosine kinase assay
Multiwell plates are precoated with a synthetic polymer substrate poly-Glu-Tyr (polyGT 4:1). The reaction is carried out in the presence of kinase buffer (10 ×: 50 mM HEPES buffer, pH 7.4, 20 mM MgCl2, 0.1 mM MnCl2, and 0.2 mM Na3VO4) supplemented with ATP and dimethyl sulfoxide (DMSO) for the positive control (C+) or SAR131675 (ranging from 3 nM–1,000 nM). ATP is used at 30 μM for VEGFR-1 and VEGFR-3 and at 15 μM for VEGFR-2. The phosphorylated poly-GT is probed with a phosphotyrosine specific monoclonal antibody (mAb) conjugated to horseradish peroxidase (HRP; 1/30,000) and developed in the dark with the HRP chromogenic substrate (OPD). The reaction is then stopped by the addition of 100 μL 1.25 M H2SO4, and absorbance is determined using an Envision spectrophotometer at 492 nm.
생체 내(In vivo)

In embryonic angiogenesis using the zebrafish model, SAR131675 efficiently impaires embryonic vasculogenesis. This compound at 100 mg/kg/d has significantly reduced the levels of VEGFR-3 and hemoglobin content by about 50%. It efficiently abrogates lymphangiogenesis and angiogenesis induced in vivo by FGF2. This chemical at a dose of 300 mg/kg is able to inhibit both VEGFR-2 and VEGFR-3 signaling. In the prevention study, 5 weeks treatment with this compound is well tolerated and the number of angiogenic islets in the pancreas of SAR131675-treated mice is significantly decreased by 42%, compared with the vehicle-treated group. In the intervention study, daily oral administration of this chemical from week 10 to week 12.5 causes a significant decrease in tumor burden by 62%. Treatment with it significantly reduces the tumor volume 24% and 50% at 30 mg/kg/d and 100 mg/kg/d, respectively.

참조