Home Stem Cells & Wnt Wnt/beta-catenin 저해제 ICG-001

연구용

ICG-001 Wnt/β-catenin 억제제

제품 번호: S2662

ICG-001은 Wnt/β-catenin/TCF 매개 전사를 길항하며 3 μM의 IC50으로 CREB-binding protein(CBP)에 특이적으로 결합하지만, 관련 전사 보조 활성제인 p300과는 결합하지 않습니다. ICG-001은 apoptosis를 유도합니다.
ICG-001 Wnt/beta-catenin 저해제 Chemical Structure

화학 구조

분자량: 548.63

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품질 관리 (Quality Control)

배치: 순도: 99.75%
99.75

함께 자주 사용되는 제품 ICG-001

(+)-JQ1

This compound, in combination with Foscenvivint and JQ1, induces strong cytotoxic effects in H3.3K27M-mutated diffuse intrinsic pontine gliomas (DIPG) cell lines.

Wnt-C59 (C59)

This compound and Wnt-C59 inhibit in vitro growth of human cholangiocarcinoma cells and reduce tumor area and number in xenograft and thioacetamide models.

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

세포주 분석 유형 농도 배양 시간 제형 활성 설명 PMID
SH-SY5Y Apoptosis Assay 50 μm 24 h DMSO blocks the protective effect of melatonin against PrP (106–126)-induced apoptotic signals 25251028
AsPC-1 Growth Inhibition Assay 1-20 μM 2/4/6 d inhibits the cell growth in a dose-dependent manner 25082960
MiaPaCa-2 Growth Inhibition Assay 1-20 μM 2/4/6 d inhibits the cell growth in a dose-dependent manner 25082960
PANC-1 Growth Inhibition Assay 1-20 μM 2/4/6 d inhibits the cell growth in a dose-dependent manner 25082960
L3.6pl Growth Inhibition Assay 1-20 μM 2/4/6 d inhibits the cell growth in a dose-dependent manner 25082960
SH-SY5Y Apoptosis Assay 10 μM 24 h inhibits the neuroprotective effects of hypoxia against PrP (106-126)-mediated neuronal cell death 23900566
HKC-8  Function Assay 10 µM 24 h abolishes β-catenin–mediated RAS induction 25012166
HK-2  Function Assay 10 µM 3 h reduced the expression of TGF-β1, α-SMA, and CTGF after treatment with HHE 23690997
HepT1 Apoptosis Assay 0-100 μM 24 h IC50=34 μM 23266718
HuH6 Apoptosis Assay 0-100 μM 24 h IC50=39 μM 23266718
MCF7 Function Assay 5 μm  inhibits leptin-mediated increased expression of Snail, Slug, and Zeb2 22270359
RLE-6TN  Function Assay 2.5/5/7.5 μM 48 h inhibits TGF-β1-induced α-SMA induction and EMT 22241478
HKC-8 Function Assay 5/10/20 μM 48 h blocks β-catenin-driven gene expression 21816937
SW480 Growth Inhibition Assay 2-100 μM IC50=5.8±0.68 μM 15782138
SW480 Function assay Inhibition of CBP binding to beta-casein in human SW480 cells by immunoblot analysis, IC50 = 1.3 μM. 23232060
A549 Antiproliferative assay 72 hrs Antiproliferative activity against human A549 cells after 72 hrs by MTT assay, GI50 = 6.1 μM. 24950489
HepG2 Antiproliferative assay 72 hrs Antiproliferative activity against human HepG2 cells after 72 hrs by MTT assay, GI50 = 12.7 μM. 24950489
LoVo Antiproliferative assay 72 hrs Antiproliferative activity against human LoVo cells after 72 hrs by MTT assay, GI50 = 15.6 μM. 24950489
HT-29 Antiproliferative assay 72 hrs Antiproliferative activity against human HT-29 cells after 72 hrs by MTT assay, GI50 = 17.2 μM. 24950489
HT29 Function assay 24 hrs Inhibition of Wnt signaling in human HT29 cells assessed as inhibition of beta-catenin-mediated Tcf/Lef transcriptional activity after 24 hrs by dual luciferase reporter gene assay relative to control, IC50 = 18.7 μM. 24950489
TC32 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 cells 29435139
A673 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells 29435139
DAOY qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY cells 29435139
BT-37 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 cells 29435139
RD qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells 29435139
MG 63 (6-TG R) qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for MG 63 (6-TG R) cells 29435139
NB1643 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells 29435139
OHS-50 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells 29435139
SJ-GBM2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells 29435139
SK-N-MC qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells 29435139
NB-EBc1 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells 29435139
LAN-5 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells 29435139
LoVo Cytotoxicity assay 10 uM 72 hrs Cytotoxicity against Wnt/beta-catenin signalling dependent human LoVo cells assessed as cell viability at 10 uM after 72 hrs by ATPlite assay ChEMBL
NCI-H1703 Function assay 10 uM 24 hrs Inhibition of TNIK in human NCI-H1703 cells transfected with lentiviral vector 7TFP assessed as reduction of GSK3 inhibitor X activated TNIK-mediated Wnt/TCF/beta-catenin-dependent transcription at 10 uM after 24 hrs by luciferase reporter assay ChEMBL
HCT116 Cytotoxicity assay 10 uM 72 hrs Cytotoxicity against Wnt/beta-catenin signalling dependent human HCT116 cells assessed as cell viability at 10 uM after 72 hrs by ATPlite assay ChEMBL
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화학 정보, 보관 및 안정성 (Chemical Information, Storage & Stability)

분자량 548.63 화학식

C33H32N4O4

 보관 (수령일로부터)
CAS 번호 780757-88-2 (relative stereochemistry); 847591-62-2 (absolute stereochemistry) SDF 다운로드 원액 보관

용해도 (Solubility)

In vitro
배치:

DMSO : 30 mg/mL (54.68 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
CBP
(Cell-free assay)
3 μM
시험관 내(In vitro)

ICG-001 has no effect on the related reporter construct, FOPFLASH, which contains mutated TCF sites. After treatment with 25μM of this compound for 8 hours, SW480 cell reduces the steady-state levels of Survivin and Cyclin D1 RNA and protein, both of which can be up-regulated by β-catenin. This compound selectively induces apoptosis in transformed cells but not in normal colon cells, reduces in vitro growth of colon carcinoma cells. It can phenotypically rescue normal nerve growth factor (NGF) -induced neuronal differentiation and neurite outgrowth in the presenilin-1 mutant cells, emphasizing the importance of the TCF/β-catenin signaling pathway on neurite outgrowth and neuronal differentiation. A recent study demonstrates that 5μM of this chemical inhibits leptin-induced EMT, invasion and tumorsphere formation in MCF7 cells.

키나아제 분석
DUAL-Luciferase 리포터 분석
Dual-Luciferase Reporter (DLR) Assay System은 이중 리포터 분석을 수행하기 위한 효율적인 수단을 제공합니다. DLRTM Assay에서는 반딧불이(Photinus pyralis) 및 Renilla(Renilla reniformis, 바다팬지라고도 함) 루시퍼라아제의 활성이 단일 샘플에서 순차적으로 측정됩니다. 반딧불이 루시퍼라아제 리포터는 Luciferase Assay Reagent II (LAR II)를 첨가하여 "glow-type" 발광 신호를 생성함으로써 먼저 측정됩니다. 반딧불이 발광을 정량화한 후, 이 반응을 퀀칭하고 동일한 튜브에 Stop & Glo® Reagent를 동시에 첨가하여 Renilla 루시퍼라아제 반응을 시작합니다. Stop & Glo® Reagent 또한 Renilla 루시퍼라아제로부터 "glow-type" 신호를 생성하며, 이는 측정 과정 동안 서서히 감소합니다. DLRTM Assay System에서 두 리포터 모두 subattomole(<10-18) 감도로 선형 분석 결과를 산출하며 실험용 숙주 세포에서 두 리포터 모두 내인성 활성이 나타나지 않습니다. 또한 DLRTM Assay의 통합 형식은 형질감염된 세포 또는 무세포 전사/번역 반응에서 두 리포터의 신속한 정량화를 제공합니다.
생체 내(In vivo)

Administration of a water-soluble analog of ICG-001 for 9 weeks reduces the formation of colon and small intestinal polyps by 42% as effectively as the nonsteroidal antiinflammatory agent, which has consistently demonstrated efficacy in this model. No overt toxicity is detected throughout the course of treatment. In the SW620 nude mouse xenograft model of tumor regression, 150 mg/kg, i.v. of this compound demonstrates a dramatic reduction in tumor volume over the 19-day course of treatment, with no mortality or weight loss. This chemical (5 mg/kg per day) significantly inhibits beta-catenin signaling and attenuates bleomycin-induced lung fibrosis in mice, while concurrently preserving the epithelium.

참조
  • [4] https://pubmed.ncbi.nlm.nih.gov/20660310/
  • [5] https://pubmed.ncbi.nlm.nih.gov/34214613/

적용 분야 (Applications)

방법 바이오마커 이미지 PMID
Western blot SOX-2 / CD44 / Survivin / EGFR / FOXM1 / EZH2 / Vimentin pβ-catenin beta-catenin / F-actin ABC / Beta-catenin / E-cadherin / N-cadherin / MMP-9 / c-MYC / Actin / Histone H3 CCNB1 / Cyclin D1
S2662-WB4
25897700

자주 묻는 질문 (Frequently Asked Questions)

질문 1:
If the compound is stored in DMSO at -80, how long would it be stable? For cell culture, how long should I change for the fresh medium with it?

답변:
It in DMSO solution can be stored at 4 degree for 1 week and -20 degree for 1 month. The best storage condition is solid powder, even at -80 the solution is not stable enough for long term storage. For cell culture, you need change medium every 48h.