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LGK974 (WNT974) PORCN inhibitor

제품 번호: S7143

LGK974 (WNT974) is a potent and specific PORCN inhibitor that inhibits Wnt signaling with an IC50 of 0.4 nM in TM3 cells, and is currently in Phase 1.
LGK974 (WNT974) PORCN inhibitor Chemical Structure

화학 구조

분자량: 396.44

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품질 관리 (Quality Control)

배치: 순도: 99.98%
99.98

함께 자주 사용되는 제품 LGK974 (WNT974)

Pictilisib (GDC-0941)

When combined with GDC-0941, it exhibits a synergistic effect in MDA-MB-231 cells.

AZD8055

Combination use of this compound and AZD-8055 reduces tumorigenesis and the immunosuppressive effects of early-stage myeloid-derived suppressor cells (eMDSCs) in mice.

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

세포주 분석 유형 농도 배양 시간 제형 활성 설명 PMID
HPAF-II  Growth Inhibition Assay 1 μM  DMSO inhibits the growth of pancreatic cancer cell lines with RNF43mutation  23847203
PaTu 8988S  Growth Inhibition Assay 1 μM  DMSO inhibits the growth of pancreatic cancer cell lines with RNF43mutation  23847203
Capan-2 Growth Inhibition Assay 1 μM  DMSO inhibits the growth of pancreatic cancer cell lines with RNF43 mutation 23847203
HPAF-II Growth Inhibition Assay 1 μM  DMSO inhibits the growth of pancreatic cancer cell lines with RNF43 mutation 23847203
PaTu8988S Growth Inhibition Assay 1 μM  DMSO inhibits the growth of pancreatic cancer cell lines with RNF43 mutation 23847203
293T  Function Assay IC50 of 0.4 nM to inhibits Wnt signaling in the aforementioned Wnt coculture assay 24277854
293T  Function Assay IC50 of 1 nM to compete off [3H]-GNF-1331 in a dose-dependent manner 24277854
HT1080 Function assay Inhibition of porcupine activity (unknown origin) expressed in human HT1080 cells assessed as suppression of Wnt3A-mediated super top flash activity by STF luciferase assay, IC50 = 0.0004 μM. 26522946
L Wnt3A, HEK293 Function assay 48 hrs Inhibition of Wnt signaling (unknown origin) expressed in mouse L Wnt3A cells co-cultured with HEK293 cells after 48 hrs by Super-top flash reporter gene assay, IC50 = 0.0009 μM. 26647303
L Wnt3A, HEK293 Function assay 48 hrs Inhibition of porcupine in mouse L Wnt3A cells co-cultured with HEK293 cells after 48 hrs by Super-top flash reporter gene assay, IC50 = 0.0009 μM. 27692509
L Wnt3A, HEK293 Function assay 48 hrs Inhibition of porcupine in mouse L Wnt3A cells co-cultured with HEK293 cells assessed as suppression of Wnt signaling after 48 hrs by Super-top flash reporter gene assay, IC50 = 0.0009 μM. 29499483
HEK293T Function assay 0.1 uM 48 hrs Inhibition of porcupine (unknown origin) in HEK293T cells transfected with pLibin-WNT3A plasmid assessed as reduction in Wnt3A secretion into cell culture medium at 0.1 uM after 48 hrs by Western blot technique 26647303
HEK293T Function assay 0.1 uM 48 hrs Inhibition of porcupine in HEK293T cells transfected with pLibin-WNT3A plasmid assessed as reduction in Wnt3A secretion into cell culture medium at 0.1 uM after 48 hrs by Western blot method 27692509
BT-12 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-12 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
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
HEK293 Function assay 100 nM 48 hrs Inhibition of porcupine in HEK293 cells transfected with pLibin-WNT3A plasmid assessed as downregulation of LRP6 phosphorylation at 100 nM after 48 hrs by Western blot analysis 29499483
HEK293T Function assay 100 nM 48 hrs Inhibition of porcupine in HEK293T cells transfected with pLibin-WNT3A plasmid assessed as reduction in Wnt3A secretion into cell culture medium at 100 nM after 48 hrs by Western blot method 29499483
PA1 Function assay 24 hrs Inhibition of porcupine-mediated Wnt/beta-catenin signaling in human PA1 cells assessed as downregulation of Axin2 mRNA expression after 24 hrs by real-time PCR analysis 29499483
HEK293 Function assay 100 nM 48 hrs Inhibition of porcupine in HEK293 cells transfected with pLibin-WNT3A plasmid assessed as downregulation of disheveled 2 phosphorylation at 100 nM after 48 hrs by Western blot analysis 29499483
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화학 정보, 보관 및 안정성 (Chemical Information, Storage & Stability)

분자량 396.44 화학식

C23H20N6O

 보관 (수령일로부터)
CAS 번호 1243244-14-5 SDF 다운로드 원액 보관

동의어 NVP-LGK974, WNT974 Smiles CC1=CC(=CN=C1C2=CC(=NC=C2)C)CC(=O)NC3=NC=C(C=C3)C4=NC=CN=C4

용해도 (Solubility)

In vitro
배치:

DMSO : 79 mg/mL (199.27 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)

특징
Orally bioavailable Porcupine-specific inhibitor that has been tested in Phase I clinical trials for treatment of malignancies dependent on Wnt ligands.
Targets/IC50/Ki
Porcn
(TM3 cells)
시험관 내(In vitro)
In the PORCN radioligand binding assay, LGK974 (WNT974) effectively displaces [3H]-GNF-1331 with an IC50 of 1 nM and shows no major cytotoxicity in cells up to 20 µM. It shows comparable inhibitory activities against all tested Wnts with IC50 ranging from 0.05 to 2.4 nM, which is consistent with the genetic loss of PORCN phenotype. This compound specifically inhibits the growth of three RNF43-mutant cell lines, HPAF-II, PaTu 8988S, and Capan-2.
생체 내(In vivo)
In a murine MMTV-Wnt1 tumor model and a human head and neck squamous cell carcinoma model (HN30), LGK974 (WNT974) (3 mg/kg) inhibits Wnt signaling in vivo and induces tumor regression without significant body weight loss in the mice. This compound (5 mg/kg, p.o., BID) also inhibits tumor growth of RNF43-mutant pancreatic tumors (HPAF-II and Capan-2) in vivo.
참조

적용 분야 (Applications)

방법 바이오마커 이미지 PMID
Western blot p-LRP6 / Axin / p-GSK3β / p-β-catenin / β-catenin NF-κB / IκB / p-IκB Nrf2 / Wnt3A / HO-1 / NQO-1 / Survivin
S7143-WB1
28128299
Immunofluorescence beta-catenin FUT8 α1, 6-fucosylation
S7143-IF1
25639201

임상시험 정보 (Clinical Trial Information)

(데이터 출처 https://clinicaltrials.gov, 업데이트 날짜 2024-05-22)

NCT 번호 모집 조건 스폰서/협력자 시작일 단계
NCT01351103 Active not recruiting
Pancreatic Cancer|BRAF Mutant Colorectal Cancer|Melanoma|Triple Negative Breast Cancer|Head and Neck Squamous Cell Cancer|Cervical Squamous Cell Cancer|Esophageal Squamous Cell Cancer|Lung Squamous Cell Cancer
Novartis Pharmaceuticals|Novartis
 December 1 2011 Phase 1

자주 묻는 질문 (Frequently Asked Questions)

질문 1:
If it is a lipophilic or hydrophilic substance?

답변:
It is a lipophilic compound.