Name: ZSTK474
Brand: Selleck Chemicals
SKU: S1072
Rating: 5 (85 reviews)

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품질 관리 (Quality Control)

배치: 순도: 99.98%

99.98

관련 타겟	Akt mTOR GSK-3 ATM/ATR DNA-PK AMPK PDPK1 PTEN PI4K PP2A
기타 PI3K 억제제	GDC-0077 (Inavolisib) SAR405 Quercetin (Sophoretin) LY294002 XL147 analogue Tersolisib (STX-478) Buparlisib (BKM120) 740 Y-P (PDGFR 740Y-P) GO-203 TFA Eganelisib (IPI-549)

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

세포주	분석 유형	농도	배양 시간	활성 설명
Sf21 insect cells	Function assay		1 h	Inhibition of bovine recombinant PI3K p110delta expressed in Sf21 insect cells using phosphatidylinositol as substrate after 1 hr by phosphoimaging, IC50=0.7 nM
human HCT116 cells	Function assay		15 mins	Inhibition of PIK3CA H1047R mutant-mediated cell signaling in human HCT116 cells expressing PTEN assessed as inhibition of insulin-induced pAkt/PKB phosphorylation at Thr308 treated for 15 mins before insulin challenge measured after 5 mins by immunoblotting, IC50=78 nM
human LNCAP cells	Proliferation assay		3 days	Antiproliferative activity against human LNCAP cells after 3 days by MTS assay, IC50=0.21 μM
human NZB5 cells	Proliferation assay		5 days	Antiproliferative activity against human NZB5 cells expressing wild type p110alpha assessed as incorporation of [3H]thymidine after 5 days, IC50=0.22 μM
human NZOV9 cells	Proliferation assay		5 days	Antiproliferative activity against human NZOV9 cells expressing p110alpha kinase Y1021C mutant assessed as incorporation of [3H]thymidine after 5 days, IC50=0.29 μM
human MDA-MB-468 cells	Cytotoxic assay		48 h	Cytotoxicity against PTEN-deficient human MDA-MB-468 cells assessed as inhibition of cell growth after 48 hrs by Cell Titer 96 assay
human A549 cells	Function assay	10 μM	1 h	Inhibition of PI3K in human A549 cells assessed as reduction in pAkt level at 10 uM after 1 hr by Western blotting analysis
human DMS114 cells	Growth inhibition assay			Growth inhibition of human DMS114 cells
human MKN74 cells	Growth inhibition assay			Growth inhibition of human MKN74 cells
human SNB78 cells	Growth inhibition assay			Growth inhibition of human SNB78 cells
human St-4 cells	Growth inhibition assay			Growth inhibition of human St-4 cells
human DU145 cells	Growth inhibition assay			Growth inhibition of human DU145 cells
human LOXIMVI cells	Growth inhibition assay			Growth inhibition of human LOXIMVI cells
human PC3 cells	Growth inhibition assay			Growth inhibition of human PC3 cells
human LOXIMVI cells	Growth inhibition assay			Growth inhibition of human LOXIMVI cells
human OVCAR3 cells	Growth inhibition assay			Growth inhibition of human OVCAR3 cells
human SKOV3 cells	Growth inhibition assay			Growth inhibition of human SKOV3 cells
human KM12 cells	Growth inhibition assay			Growth inhibition of human KM12 cells
human HT-29 cells	Growth inhibition assay			Growth inhibition of human HT-29 cells
human HCT15 cells	Growth inhibition assay			Growth inhibition of human HCT15 cells
human NCI-H226 cells	Growth inhibition assay			Growth inhibition of human NCI-H226 cells
human NCI-H522 cells	Growth inhibition assay			Growth inhibition of human NCI-H522 cells
human A549 cells	Growth inhibition assay			Growth inhibition of human A549 cells
human HCC2998 cells	Growth inhibition assay			Growth inhibition of human HCC2998 cells
human SNB75 cells	Growth inhibition assay			Growth inhibition of human SNB75 cells
human OVCAR4 cells	Growth inhibition assay			Growth inhibition of human OVCAR4 cells
human OVCAR5 cells	Growth inhibition assay			Growth inhibition of human OVCAR5 cells
human OVCAR8 cells	Growth inhibition assay			Growth inhibition of human OVCAR8 cells
human SKOV3 cells	Growth inhibition assay			Growth inhibition of human SKOV3 cells
human ACHN cells	Growth inhibition assay			Growth inhibition of human ACHN cells
클릭하여 더 많은 세포주 실험 데이터 보기

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

분자량	417.41	화학식	C₁₉H₂₁F₂N₇O₂	보관 (수령일로부터)	3년-20°C분말
CAS 번호	475110-96-4	SDF 다운로드		원액 보관	1년-80°C용매에 보관 1개월-20°C용매에 보관
동의어	N/A			Smiles	C1COCCN1C2=NC(=NC(=N2)N3C4=CC=CC=C4N=C3C(F)F)N5CCOCC5

용해도 (Solubility)

In vitro
배치:

DMSO : 15 mg/mL (35.93 mM)
(수분으로 오염된 DMSO는 용해도를 감소시킬 수 있습니다. 신선하고 무수 DMSO를 사용하십시오.)

Water : Insoluble

Ethanol : Insoluble

DMSO : 21 mg/mL (50.31 mM)
(수분으로 오염된 DMSO는 용해도를 감소시킬 수 있습니다. 신선하고 무수 DMSO를 사용하십시오.)

Water : Insoluble

Ethanol : Insoluble

DMSO : 21 mg/mL (50.31 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:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	0.5% hydroxyethyl cellulose Selleck 연구소에서 검증되었습니다. 이 제형에 대한 조정이 필요한 경우 맞춤 테스트를 위해 당사 영업팀에 문의하십시오.	10.000mg/ml (23.96mM)	Taking the 1 mL working solution as an example, take 10 mg of this product, add it to 1 ml of 0.5% hydroxyethyl cellulose clear solution, and mix evenly to form a uniform suspension. The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

생체 내 제형 계산기 (투명한 용액)

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

투여량: mg/kg 동물 평균 체중: g 동물당 투여량:μL 동물 수:

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	First orally administered PI3K inhibitor used in vivo.
Targets/IC₅₀/Ki	PI3Kδ (Cell-free assay) 4.6 nM PI3Kα (Cell-free assay) 16 nM PI3K (Cell-free assay) 37 nM PI3Kβ (Cell-free assay) 44 nM PI3Kγ (Cell-free assay) 49 nM
시험관 내(In vitro)	ZSTK474 at 1 μM potently reduces PI3K activity to 4.7% of the control level, whereas LY2194002 only reduces the activity to 44.6% of the control. This compound inhibits the activities of recombinant p110β, -γ, and -δ with IC50 of 17 nM, 53 nM, and 6 nM, respectively. It shows potent antiproliferative activity against a panel of 39 human cancer cell lines with mean GI50 of 0.32 μM, more effectively than that of LY294002 or wortmannin with mean GI50 of 7.4 μM or 10 μM, respectively. This chemical treatment at 1 μM blocks membrane ruffling and generation of PIP3 induced by platelet-derived growth factor in murine embryonic fibroblasts (MEFs). It at 10 μM induces apoptosis in OVCAR3 cells, and induces complete G1-phase arrest but not apoptosis in A549 cells. This compound treatment at 0.5 μM significantly decreases the level of phosphorylated Akt and GSK-3β, as well as the cyclin D1 protein expression. It also inhibits the phosphorylation of other downstream signaling components that are involved in regulating cell proliferation including FKHRL1, FKHR, TSC-2, mTOR, and p70S6K in a dose-dependent manner. This chemical does not inhibit mTOR at 0.1 μM, and even at a concentration of 100 μM, it inhibits mTOR activity less than 40%. It blocks VEGF-induced cell migration and the tube formation in human umbilical vein endothelial cells (HUVECs), and inhibits the expression of HIF-1α and secretion of VEGF in RXF-631L cells, exhibiting potent in vitro antiangiogenic activity. This compound treatment inhibits the production of IFNγ and IL-17 in concanavalin A-activated T cells, and inhibits the proliferation and PGE(2) production by fibroblast-like synovial cells (FLS).
키나아제 분석	PI3K 활성 억제
키나아제 분석	A549 세포를 20 mM Tris-HCl(pH 7.5), 150 mM NaCl, 5 mM EDTA 및 1% Igepal CA-630을 포함하는 완충액에서 용해하고, 용해물을 20,000 g 및 4 °C에서 10분간 원심분리한 후 상층액을 세포 용해물(단백질 = 2-4 mg/mL)로 사용합니다. PI3K를 면역침전시키기 위해 200 μL의 세포 용해물을 anti-p85 다클론 항체 및 protein G-agarose(5 μL)와 함께 배양합니다. PI3Kα, PI3Kβ 및 PI3Kδ는 anti-p85 다클론 항체에 의해 면역침전될 수 있습니다. 면역침전물을 포함하는 아가로스 비드는 완충액 A(20 mM Tris-HCl, pH 7.5, 150 mM NaCl, 5 mM EDTA 및 1% Igepal CA-630)로 2회, 완충액 B(500 mM LiCl 및 100 mM Tris-HCl, pH 7.5)로 1회, 증류수로 1회, 완충액 C(100 mM NaCl 및 20 mM Tris-HCl, pH 7.5)로 1회 세척합니다. 면역침전물을 200 μg/mL의 포스파티딜이노시톨을 포함하는 20 μL의 완충액 C에 현탁합니다. 이 혼합물을 25 °C에서 5분간 이 화합물의 농도를 높여가며 사전 배양합니다. [γ-³²P]ATP(분석 혼합물당 2 μCi; 최종 농도 20 μM)와 MgCl₂(최종 농도 20 mM)를 첨가하여 반응을 시작합니다. 반응 혼합물을 25 °C에서 20분간 배양합니다. 포스파티딜이노시톨의 인산화 산물을 박층 크로마토그래피로 분리하고 방사선 자기기록법으로 시각화합니다. 포스파티딜이노시톨-3-인산 영역을 플레이트에서 긁어내고 액체 섬광 분광법으로 방사능을 측정합니다. 이 화학 물질에 대한 억제 수준은 이 화합물 없이 얻은 ³²P 분당 계수(cpm)의 백분율로 결정합니다.
생체 내(In vivo)	Oral administration of ZSTK474 inhibits the growth of subcutaneously implanted mouse B16F10 melanoma tumors in a dose-dependent manner, producing tumor regression of 28.5%, 7.1%, or 4.9% on day 14 at 100, 200, or 400 mg/kg, respectively, which is superior to that of the four major anticancer drugs at their respective maximum tolerable doses with tumor regression of 96%, 35.7%, 24%, or 68.3%, respectively. This compound treatment at 400 mg/kg completely inhibits the growth of A549, PC-3, and WiDr xenografts in mice, and induces the regression of A549 xenograft tumors. It significantly inhibits tumor growth in the RXF-631L xenograft model, correlated with a significantly reduced number of microvessels in the treated mice. Oral administration of this chemical ameliorates the progression of adjuvant-induced arthritis (AIA) in rats.
참조	[1] https://pubmed.ncbi.nlm.nih.gov/16622124/ [2] https://pubmed.ncbi.nlm.nih.gov/17711503/ [3] https://pubmed.ncbi.nlm.nih.gov/19144509/ [4] https://pubmed.ncbi.nlm.nih.gov/19372588/ [5] https://pubmed.ncbi.nlm.nih.gov/22039466/ [6] https://pubmed.ncbi.nlm.nih.gov/22349137/

적용 분야 (Applications)

방법	바이오마커	이미지	PMID
Western blot	p-PDK1 / p-GSK3β / p-AKT / AKT P-gp / MRP1 p-Rb / p27 / Cyclin D1 HIF-1α / HIF-1β		28388564
Growth inhibition assay	Cell viability		28388564

임상시험 정보 (Clinical Trial Information)

(데이터 출처 https://clinicaltrials.gov, 업데이트 날짜 2017-07-06)

NCT 번호	모집	조건	스폰서/협력자	시작일	단계
NCT01682473	COMPLETED	Neoplasms	Zenyaku Kogyo Co., Ltd.	2012-09-20	PHASE1
NCT01280487	COMPLETED	Neoplasms	Zenyaku Kogyo Co., Ltd.	2011-01	PHASE1

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):

ZSTK474 PI3K 저해제

분자량: 417.41

품질 관리 (Quality Control)

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

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

용해도 (Solubility)

몰농도 계산기

생체 내 제형 계산기 (투명한 용액)

작용 메커니즘 (Mechanism of Action)

적용 분야 (Applications)

임상시험 정보 (Clinical Trial Information)

ZSTK474 PI3K 저해제

분자량: 417.41

품질 관리 (Quality Control)

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

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

용해도 (Solubility)

몰농도 계산기

생체 내 제형 계산기 (투명한 용액)

작용 메커니즘 (Mechanism of Action)

적용 분야 (Applications)

임상시험 정보 (Clinical Trial Information)

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