Home Metabolism FXR agonist GW4064

연구용

GW4064 FXR agonist

제품 번호S2782

GW4064 is an agonist of farnesoid X receptor (FXR) with EC50 of 65 nM in CV1 cell line and displays no activity at other nuclear receptors at concentrations up to 1 μM. This compound stimulates autophagy in MCF-7 cells.
GW4064 FXR agonist Chemical Structure

화학 구조

분자량: 542.84

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품질 관리 (Quality Control)

배치: 순도: 99.80%
99.80

세포 배양, 처리 및 작업 농도
(Cell Culture, Treatment & Working Concentration)

세포주 분석 유형 농도 배양 시간 제형 활성 설명 PMID
HEK293 Function assay Agonistic activity at FXR in HEK293 cells by GAL4 transactivation activity, EC50 = 0.07 μM. 17292610
CV1 Function assay Agonist activity at FXR expressed in african green monkey CV1 cells by luciferase reporter transient transfection assay, EC50 = 0.065 μM. 18621523
CV1 Function assay Agonist activity at human FXR transfected in african green monkey CV1 cells by luciferase reporter gene transient transfection assay, EC50 = 0.065 μM. 19410460
CV1 Function assay Increase in human FXR-mediated transient transcription of luciferase reporter gene transfected in african green monkey CV1 cells, EC50 = 0.065 μM. 19586769
HEK293 Function assay Agonist activity at human full length FXR transfected in HEK293 cells coexpressing pTRexDest/pGL2promotor assessed as luciferase activity by direct reporter cellular assay, EC50 = 0.03 μM. 20638278
HEK293 Function assay Agonist activity at human GST-fused FXR LBD expressed in HEK293 cells coexpressing GAL4-DNA bindig domain and pFRluc by mammalian one-hybrid assay, EC50 = 0.035 μM. 20638278
CV-1 Function assay Agonist activity at human FXR LBD iexpressed in monkey CV-1 cells assessed as transactivation of luciferase reporter gene expression, EC50 = 0.065 μM. 21256005
CV1 Function assay Agonist activity at human FXR LBD transfected in african green monkey CV1 cells after overnight incubation by luciferase reporter gene assay, EC50 = 0.065 μM. 21890356
HEK293 Function assay Agonist activity at human recombinant FXR expressed in HEK293 cells coexpressing CMX-GAL4N by luciferase reporter gene assay, EC50 = 0.07 μM. 22583617
HEK293 Function assay Agonist activity at human FXR expressed in HEK293 cells by luciferase reporter gene assay, EC50 = 0.026 μM. 25305688
CV1 Function assay Agonist activity at FXR (unknown origin) transfected into african green monkey CV1 cells assessed as ligand-mediated transcription by luciferase reporter/ transient transfection assay, EC50 = 0.065 μM. 25499883
HeLa Function assay 24 hrs Agonist activity at human full length FXR expressed in HeLa cells cotransfected with pSG5-human RXR after 24 hrs by Dual-Glo luciferase reporter gene assay, EC50 = 0.51 μM. 25934227
HEK293 Function assay Agonist activity at human FXR transfected in HEK293 cells assessed as transcriptional activity by luciferase reporter gene assay, EC50 = 0.373 μM. 26568144
HEK-293 Function assay Agonist activity at C-terminal Gal4-tagged human FXR (187 to 472 residues) expressed in HEK-293 cells co-expressing pFRluc by mammalian one hybrid assay, EC50 = 0.035 μM. 27268696
insect cells Function assay 1 hr Agonist activity at recombinant human GST-tagged FXR ligand binding domain (193 to 472 residues) expressed in baculovirus infected insect cells assessed as induction of interaction with biotin labelled SRC-1 after 1 hr by HTRF assay, EC50 = 0.019 μM. 29148806
HEK293T Function assay 24 hrs Agonist activity at human FXR expressed in HEK293T cells assessed as BSEP promoter driven cellular transcriptional activity after 24 hrs by luciferase reporter gene assay, EC50 = 0.095 μM. 29148806
HepG2 Function assay 1 uM 18 hrs Decrease in CYP7A1 gene expression in human HepG2 cells at 1 uM after 18 hrs by RT-PCR 17963371
Caco-2 Function assay 1 uM 6 days Activation of IBABP gene expression in human Caco-2 cells at 1 uM after 6 days by RT-PCR 17963371
HepG2 Function assay 1 uM 18 hrs Activation of BSEP gene expression in human HepG2 cells at 1 uM after 18 hrs by RT-PCR 17963371
Huh7 Function assay 1 uM 18 hrs Activation of SHP gene expression in human Huh7 cells at 1 uM after 18 hrs by RT-PCR 17963371
Huh7 Function assay 1 uM 18 hrs Activation of BSEP gene expression in human Huh7 cells at 1 uM after 18 hrs by RT-PCR 17963371
HepG2 Function assay 10 uM Induction of FXR-mediated SHP mRNA expression in serum-starved human HepG2 cells at 10 uM measured after overnight incubation by qPCR analysis 27372840
HepG2 Function assay 10 uM 10 mins Induction of FXR-mediated Akt-phosphorylation at S473 site in serum-starved human HepG2 cells at 10 uM measured after 10 mins by western blot analysis 27372840
HepG2 Function assay 10 uM 10 mins Induction of FXR-mediated Akt-phosphorylation in serum-starved human HepG2 cells assessed as increase in GSK-3beta-phosphorylation at 10 uM measured after 10 mins by western blot analysis 27372840
HepG2 Function assay 10 uM Activation of FXR in human HepG2 cells assessed as upregulation of SHP mRNA expression at 10 uM by RT-PCR method 30031618
HepG2 Function assay 10 uM Activation of FXR in human HepG2 cells assessed as upregulation of FXR mRNA expression at 10 uM by RT-PCR method 30031618
HepG2 Function assay 10 uM Activation of FXR in human HepG2 cells assessed as downregulation of SREBP-1c mRNA expression at 10 uM by RT-PCR method 30031618
3T3L1 Function assay 10 uM Reduction in lipid accumulation in mouse 3T3L1 cells at 10 uM by Oil Red O staining-based absorbance method relative to control 30342957
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화학 정보, 보관 및 안정성 (Chemical Information, Storage & Stability)

분자량 542.84 화학식

C28H22Cl3NO4

 보관 (수령일로부터)
CAS 번호 278779-30-9 SDF 다운로드 원액 보관

동의어 N/A Smiles CC(C)C1=C(C(=NO1)C2=C(C=CC=C2Cl)Cl)COC3=CC(=C(C=C3)C=CC4=CC(=CC=C4)C(=O)O)Cl

용해도 (Solubility)

In vitro
배치:

DMSO : 100 mg/mL (184.21 mM)
(수분으로 오염된 DMSO는 용해도를 감소시킬 수 있습니다. 신선하고 무수 DMSO를 사용하십시오.)

Water : Insoluble

Ethanol : 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)

Targets/IC50/Ki
FXR
(CV1)
65 nM(EC50)
시험관 내(In vitro)

GW 4064 is a full agonist with EC50 values of 80 and 90 nM, respectively, in CV-1 cells transfected with mouse and human FXR expression vectors and an established reporter gene. There is no activity of this compound on other nuclear receptors, including the retinoic acid receptor, at concentrations up to 1 μM. Thus, this chemical is a potent and selective nonsteroidal FXR agonist.

키나아제 분석
FXR Transient Transfection Assay
CV1 cells are maintained in DMEM high glucose medium. The CV1 cells are harvested 72 hours before transfection and plated in DMEM-F12 phenol red free medium containing 5% charcoal/dextran treated fetal bovine serum and 2 mM glutamine. On the day of transfection, the CV1 cells are harvested in DMEM-F12 phenol red free medium containing 5% charcoal/dextran treated fetal bovine serum and 2 mM glutamine, counted and seeded into a T-175 cm2 flask at a density of 14 million cells per flask before adding the transfection mix. The FuGENE® 6 transfection mix containing 0.55 μg pFA-CMV-GAL4-human FXR LBD expression plasmid, 10.92 μg of the (UAS)-tk-Luciferase reporter plasmid, 20.75 μg of pBluescript II KS+, and 3.82 μg of a human steroid receptor co-activator (SRC-1) construct is incubated and then added to the CV1 cells for overnight incubation in incubator. The transfected CV1 cells are harvested in DMEM-F12 phenol red free medium containing 5% charcoal/dextran treated fetal bovine serum and 2 mM glutamine. Transfected cells are added at a concentration of 3750 cells/well to 384-well plates containing ligands. Luciferase expression is measured using Steady-Glo?Luciferase Assay System 24 hr after incubation with ligand. This compound is used as the control, and data are normalized to this compound as % control.
생체 내(In vivo)

Pharmacokinetic analysis in rats shows that GW 4064 possesses an oral bioavailability of 10% with a t1/2 = 3.5 h. Fisher rats are dosed with this compound by oral gavage. After 7 days, a dose-dependent lowering of serum triglycerides is observed in the rats receiving this chemical, with an ED50 = 20 mg/kg.

참조

적용 분야 (Applications)

방법 바이오마커 이미지 PMID
Western blot PTEN / p-AKT / AKT p-EGFR / EGFR / p-ERK / ERK / p-Src / Src SOCS3 / p21 / p-STAT3 / STAT3
S2782-WB1
25187826
Growth inhibition assay Cell proliferation
S2782-viability1
25187826