Name: GSK690693
Brand: Selleck Chemicals
SKU: S1113
Rating: 5 (126 reviews)

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품질 관리 (Quality Control)

배치: 순도: 99.09%

99.09

관련 타겟	PI3K mTOR GSK-3 ATM/ATR DNA-PK AMPK PDPK1 PTEN PI4K PP2A
기타 Akt 억제제	SC79 AZD5363 (Capivasertib) MK-2206 Dihydrochloride Ipatasertib (GDC-0068) Perifosine Triciribine (API-2) Afuresertib (GSK2110183) CCT128930 A-674563 HCl AKTi-1/2 (AKT Inhibitor VIII)

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

세포주	분석 유형	배양 시간	활성 설명	PMID
LNCaP	Proliferation assay		Antiproliferative activity against human LNCaP cells, IC50=20 nM	18800763
BT474	Proliferation assay		Antiproliferative activity against human BT474 cells, IC50=50 nM	18800763
Sf9	Function assay		Inhibition of human recombinant ROCK1 expressed in Sf9 cells, IC50=0.89 μM	18800763
NCI-H460	Growth inhibition assay	72 h	Growth inhibition of human NCI-H460 cells after 72 hrs by coulter counter method, IC50=5.4 μM	24900862
PC3	Proliferation assay	72 h	Antiproliferative activity against human PC3 cells after 72 hrs by MTT assay, IC50=15.5 μM	24308997
HFF	Cytotoxic assay		Cytotoxicity against HFF cells, IC50=16.3 μM	18800763
LNCAP	Antiproliferative assay		Antiproliferative activity against human LNCAP cells, IC50 = 0.021 μM.	19179070
BT474	Antiproliferative assay		Antiproliferative activity against human BT474 cells, IC50 = 0.069 μM.	19179070
BT474	Function assay		Inhibition of GSK3-beta phosphorylation in human BT474 cells, IC50 = 0.138 μM.	19179070
JVM2	Antiproliferative assay	72 hrs	Antiproliferative activity against human JVM2 cells after 72 hrs by CellTiter Glo assay, IC50 = 1.6 μM.	28704757
JeKo1	Antiproliferative assay	72 hrs	Antiproliferative activity against human JeKo1 cells after 72 hrs by CellTiter Glo assay, IC50 = 3 μM.	28704757
Z138	Antiproliferative assay	72 hrs	Antiproliferative activity against human Z138 cells after 72 hrs by CellTiter Glo assay, IC50 = 3.1 μM.	28704757
SP49	Antiproliferative assay	72 hrs	Antiproliferative activity against human SP49 cells after 72 hrs by CellTiter Glo assay, IC50 = 4.8 μM.	28704757
Maver1	Antiproliferative assay	72 hrs	Antiproliferative activity against human Maver1 cells after 72 hrs by CellTiter Glo assay, IC50 = 5.1 μM.	28704757
C6	Function assay	24 hrs	Inhibition of Akt in rat C6 cells after 24 hrs by ELISA, IC50 = 6.97 μM.	29966916
C6	Cytotoxicity assay	24 hrs	Cytotoxicity against rat C6 cells assessed as decrease in cell viability after 24 hrs by MTT assay, IC50 = 14.5 μM.	29966916
A549	Function assay	24 hrs	Inhibition of Akt in human A549 cells after 24 hrs by ELISA, IC50 = 17.33 μM.	29966916
Mino	Antiproliferative assay	72 hrs	Antiproliferative activity against human Mino cells after 72 hrs by CellTiter Glo assay, IC50 = 20.8 μM.	28704757
A673	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells	29435139
RD	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells	29435139
NB1643	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 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
MCL	Antiproliferative assay	24 hrs	Antiproliferative activity against primary human MCL cells up to 60 uM after 24 hrs by CellTiter Glo assay	28704757
클릭하여 더 많은 세포주 실험 데이터 보기

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

분자량	425.48	화학식	C₂₁H₂₇N₇O₃	보관 (수령일로부터)	3년-20°C분말
CAS 번호	937174-76-0	SDF 다운로드		원액 보관	1년-80°C용매에 보관 1개월-20°C용매에 보관
동의어	N/A			Smiles	CCN1C2=C(C(=NC=C2OCC3CCCNC3)C#CC(C)(C)O)N=C1C4=NON=C4N

용해도 (Solubility)

In vitro
배치:

DMSO : 21 mg/mL (49.35 mM)
(수분으로 오염된 DMSO는 용해도를 감소시킬 수 있습니다. 신선하고 무수 DMSO를 사용하십시오.)

Water : Insoluble

Ethanol : Insoluble

DMSO : 21 mg/mL (49.35 mM)
(수분으로 오염된 DMSO는 용해도를 감소시킬 수 있습니다. 신선하고 무수 DMSO를 사용하십시오.)

Water : Insoluble

Ethanol : Insoluble

DMSO : 21 mg/mL (49.35 mM)
(수분으로 오염된 DMSO는 용해도를 감소시킬 수 있습니다. 신선하고 무수 DMSO를 사용하십시오.)

Water : Insoluble

Ethanol : Insoluble

DMSO : 25 mg/mL (58.75 mM)
(수분으로 오염된 DMSO는 용해도를 감소시킬 수 있습니다. 신선하고 무수 DMSO를 사용하십시오.)

Water : Insoluble

Ethanol : Insoluble

DMSO : 40 mg/mL (94.01 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.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Selleck 연구소에서 검증되었습니다. 이 제형에 대한 조정이 필요한 경우 맞춤 테스트를 위해 당사 영업팀에 문의하십시오.	3.000mg/ml (7.05mM)	Taking the 1 mL working solution as an example, add 50 μL of 60 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to make it clear; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. 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.
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)

Targets/IC₅₀/Ki	ULK1 STING AMPK Akt1 (Cell-free assay) 2 nM PKCη (Cell-free assay) 2 nM PKCθ (Cell-free assay) 2 nM PrkX (Cell-free assay) 5 nM Akt3 (Cell-free assay) 9 nM Akt2 (Cell-free assay) 13 nM PKCδ (Cell-free assay) 14 nM PKCβ (Cell-free assay) 19 nM PKCε (Cell-free assay) 21 nM PKA (Cell-free assay) 24 nM PKG1β (Cell-free assay) 33 nM
시험관 내(In vitro)	GSK690693 is very selective for the Akt isoforms versus the majority of kinases in other families. However, this compound is less selective for members of the AGC kinase family including PKA, PrkX, and PKC isozymes with IC50 of 24 nM, 5 nM, and 2-21 nM, respectively. It also potently inhibits AMPK and DAPK3 from the CAMK family with IC50 of 50 nM and 81 nM, respectively, and PAK4, 5, and 6 from the STE family with IC50 of 10 nM, 52 nM, and 6 nM, respectively. This chemical inhibits the phosphorylation of GSK3β in tumor cells with IC50 ranging from 43 nM to 150 nM. Its treatment leads to a dose-dependent increase in the nuclear accumulation of the transcription factor FOXO3A. This compound potently inhibits the proliferation of T47D, ZR-75-1, BT474, HCC1954, MDA-MB-453, and LNCaP cells with IC50 of 72 nM, 79 nM, 86 nM, 119 nM, 975 nM, and 147 nM, respectively. Its treatment induces apoptosis at concentrations >100 nM in both LNCaP and BT474 cells. Consistent with the role of AKT in cell survival, it induces apoptosis in sensitive ALL cell lines.
키나아제 분석	In vitro kinase 분석
키나아제 분석	His-tag이 부착된 전장 Akt1, 2 또는 3은 바큘로바이러스로부터 발현 및 정제됩니다. 활성화는 Thr308을 인산화하기 위해 정제된 PDK1을 사용하고 Ser473을 인산화하기 위해 정제된 MK2를 사용하여 수행됩니다. Akt의 시간 의존적 억제를 보다 정확하게 측정하기 위해, 활성화된 Akt 효소를 기질 첨가로 반응을 시작하기 전 실온에서 30분 동안 다양한 농도의 GSK690693과 함께 배양합니다. 최종 반응액에는 5 nM~15 nM의 Akt1, 2 및 3 효소, 2 μM ATP, 0.15 μCi/μL[γ-³³P]ATP, 1 μM 펩타이드(Biotin-aminohexanoicacid-ARKR-ERAYSFGHHA-amide), 10 mM MgCl₂, 25 mM MOPS(pH 7.5), 1 mM DTT, 1 mM CHAPS 및 50 mM KCl이 포함됩니다. 반응물을 실온에서 45분 동안 배양한 후, EDTA를 포함하는 PBS(최종 농도, 2 mg/mL 비드 및 75 mM EDTA) 내 Leadseeker 비드로 반응을 종료합니다. 그 후 플레이트를 밀봉하고 비드가 최소 5시간 동안 가라앉도록 둔 다음, Viewlux Imager를 사용하여 생성물 형성을 정량화합니다.
생체 내(In vivo)	A single administration of GSK690693 inhibits GSK3β phosphorylation in human breast carcinoma (BT474) xenografts in a dose- and time-dependent manner. Similarly, this compound induces a reduction in phosphorylation of the Akt substrates, PRAS40, and FKHR/FKHRL1. It also results in an acute increase in blood glucose, returning to baseline 8 to 10 hours after drug administration. Administration of this chemical induces reductions in phosphorylated Akt substrates in vivo, and potently inhibits the growth of human SKOV-3 ovarian, LNCaP prostate, and BT474 and HCC-1954 breast carcinoma xenografts, with maximal inhibition of 58% to 75% at the dose of 30 mg/kg/day. This compound exhibits efficacy irrespective of the mechanism of Akt activation involved. It is most effective in delaying tumor progression in Lck-MyrAkt2 mice expressing a membrane-bound, constitutively active form of Akt.
참조	[1] https://pubmed.ncbi.nlm.nih.gov/18381444/ [2] https://pubmed.ncbi.nlm.nih.gov/19064730/ [3] https://pubmed.ncbi.nlm.nih.gov/20075391/ [4] https://pubmed.ncbi.nlm.nih.gov/29694889/

적용 분야 (Applications)

방법	바이오마커	이미지	PMID
Western blot	p-Akt / Akt / p-GSK3 / p-mTOR / mTOR / p-p70S6K / p-FoxO3a / p-FoxO1 pPRAS40 / PRAS40 / pBAD / BAD		20075391
Growth inhibition assay	Cell viability		20075391

임상시험 정보 (Clinical Trial Information)

(데이터 출처 https://clinicaltrials.gov, 업데이트 날짜 2015-04-17)

NCT 번호	모집	조건	스폰서/협력자	시작일	단계
NCT00666081	WITHDRAWN	Cancer	GlaxoSmithKline	2008-04	PHASE1
NCT00493818	TERMINATED	Cancer	GlaxoSmithKline	2007-04	PHASE1
NCT00666081	Withdrawn	Cancer	GlaxoSmithKline	2008-04	Phase 1
NCT00493818	Terminated	Cancer	GlaxoSmithKline	2007-04	Phase 1

자주 묻는 질문 (Frequently Asked Questions)

질문 1:
Why did pAKT increase after treatment with it?

답변:
It actually inhibits AKT, but does not necessarily decrease p-Akt level. Treatment with this compound caused AKT hyper phosphorylation which has already been reported in some papers. (For example, http://www.bloodjournal.org/content/113/8/1723.short?sso-checked=true). To test the inhibition of AKT activity, you might have to look at the level of AKT substrates.

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):

GSK690693 pan-Akt 억제제

분자량: 425.48

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)

자주 묻는 질문 (Frequently Asked Questions)

GSK690693 pan-Akt 억제제

분자량: 425.48

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)

자주 묻는 질문 (Frequently Asked Questions)

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