GSK461364

別名: GSK461364A

目錄號(hào)：S2193 Purity: 99.97%

GSK461364 (GSK461364A)抑制純化的Plk1，無(wú)細(xì)胞試驗(yàn)中K_i為2 nM。比作用于Plk2/3選擇性高1000倍。

GSK461364 Chemical Structure

CAS: 929095-18-1

規(guī)格	價(jià)格	庫(kù)存
10mM (1mL in DMSO)	4032.81	現(xiàn)貨
10mg	3127.94	現(xiàn)貨
50mg	8845.2	現(xiàn)貨
200mg	16298.1	現(xiàn)貨
1g	32678.1	現(xiàn)貨
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產(chǎn)品質(zhì)控

批次：純度： 99.97%

99.97

GSK461364相關(guān)產(chǎn)品

相關(guān)靶點(diǎn)	PLK1 PLK2 PLK3 PLK4	點(diǎn)擊展開(kāi)
相關(guān)產(chǎn)品	BI 2536 Volasertib Rigosertib (ON-01910) Onvansertib (NMS-P937) SBE 13 HCl Ro3280 CFI-400945 HMN-214 MLN0905 Poloxin	點(diǎn)擊展開(kāi)
相關(guān)化合物庫(kù)	激酶抑制劑庫(kù) PI3K/Akt 抑制劑庫(kù) MAPK抑制劑庫(kù) DNA損傷/ DNA修復(fù)化合物庫(kù) 細(xì)胞周期化合物庫(kù)	點(diǎn)擊展開(kāi)

細(xì)胞實(shí)驗(yàn)數(shù)據(jù)示例

細(xì)胞系	實(shí)驗(yàn)類型	孵育時(shí)間	活性描述	文獻(xiàn)信息
human MV4-11 cells	Cytotoxicity assay	24 h	Cytotoxicity against human MV4-11 cells after 24 hrs by CellTiter-Blue assay, GI50=0.679 μM	26191363
HEK293T	Antiproliferative assay	72 hrs	Antiproliferative activity against HEK293T cells measured after 72 hrs by CellTiter-Blue assay, IC50=0.001μM	28792760
MDA-MB-231	Antiproliferative assay	72 hrs	Antiproliferative activity against human MDA-MB-231 cells measured after 72 hrs by CellTiter-Blue assay, IC50=0.001μM	28792760
MM1S	Antiproliferative assay	72 hrs	Antiproliferative activity against human MM1S cells measured after 72 hrs by CellTiter-Blue assay, IC50=0.001μM	28792760
MDA-MB-23	Function assay	6 hrs	Inhibition of PLK1 in human MDA-MB-23 cells assessed as decrease in TCTP phosphorylation after 6 hrs by Western blot method, IC50<0.1μM	28792760
HEK293T	Function assay	6 hrs	Inhibition of PLK1 in HEK293T cells assessed as decrease in TCTP phosphorylation after 6 hrs by Western blot method, IC50<0.1μM	28792760
TC32	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 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
A673	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 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
BT-37	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 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
U-2 OS	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for U-2 OS cells	29435139
SK-N-SH	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH cells	29435139
NB1643	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 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
BT-12	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-12 cells	29435139
Rh18	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh18 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
NB1643	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for NB1643 cells	29435139
A673	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for A673 cells)	29435139
SK-N-MC	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SK-N-MC cells	29435139
BT-12	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for BT-12 cells	29435139
LAN-5	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for LAN-5 cells	29435139
NB-EBc1	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for NB-EBc1 cells	29435139
SJ-GBM2	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SJ-GBM2 cells	29435139
BT-37	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for BT-37 cells	29435139
TC32	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for TC32 cells	29435139
MG 63 (6-TG R)	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for MG 63 (6-TG R) cells	29435139
fibroblast cells	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for control Hh wild type fibroblast cells	29435139
Rh41	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh41 cells	29435139
Rh18	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh18 cells	29435139
Rh30	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh30 cells	29435139
OHS-50	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for OHS-50 cells	29435139
SK-N-SH	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SK-N-SH cells	29435139
點(diǎn)擊查看更多細(xì)胞系數(shù)據(jù)

生物活性

產(chǎn)品描述

GSK461364 (GSK461364A)抑制純化的Plk1，無(wú)細(xì)胞試驗(yàn)中K_i為2 nM。比作用于Plk2/3選擇性高1000倍。

特性

GSK461364是有效的，可逆的ATP競(jìng)爭(zhēng)性的Plk1選擇性抑制劑，作用于Plk1比作用于Plk2和Plk3選擇性至少高390倍，而比作用于一組48種其他激酶選擇性高1×10³倍。

靶點(diǎn)

PLK1 ^[1]
(Cell-free assay)

2.2 nM(Ki)

體外研究(In Vitro)
體外研究活性	GSK461364作用于非細(xì)胞分裂細(xì)胞，從多起點(diǎn)抑制癌細(xì)胞系增殖。^[1] 野生型p53的RNA沉默提高GSK461364的抗增殖活性。許多癌癥療法對(duì)p53野生型患者更有效, p53缺陷腫瘤對(duì)GSK461364的高度敏感性可提供治療腫瘤的機(jī)會(huì)。GSK461364是噻吩酰胺，在體外，抑制純化的Plk1酶，K_i為2 nM，作用于Plk1比作用于 Plk2和 Plk3選擇性高100多倍。GSK461364是有效的細(xì)胞增殖抑制劑，低于100 nM 時(shí)作用于大部分細(xì)胞系，抑制50% 生長(zhǎng)(GI50)，作用于人無(wú)增殖細(xì)胞系具有有限的毒性。GSK461364抑制細(xì)胞周期進(jìn)展是濃度依賴性的，高濃度時(shí)，使細(xì)胞在G2期發(fā)生延遲，較低濃度時(shí)使細(xì)胞停在M 期。目前, GSK461364按劑量遞增方式首次用在人體試驗(yàn)階段。攜帶TP53基因突變的細(xì)胞系對(duì) GSK461364更敏感，且作用于一些p53野生型(WT)細(xì)胞，通過(guò)RNA沉默抑制p53 反應(yīng)，使敏感性增加。而且, 這些更敏感的細(xì)胞系染色體不穩(wěn)定性提高，這是與TP53突變相關(guān)的一個(gè)特點(diǎn)。^[2] 在臨床前期研究中, GSK461364作用于多種(>120)腫瘤細(xì)胞系，具有抗增殖活性，且有效抑制這些細(xì)胞系中的 83%和91%細(xì)胞增殖，IC50分別低于50和100 nM。^[3]
激酶實(shí)驗(yàn)	酶實(shí)驗(yàn)
激酶實(shí)驗(yàn)	使用Z-Lyte 檢測(cè)試劑盒(Ser/Thr肽 16)進(jìn)行激酶反應(yīng)，終實(shí)驗(yàn)體積為10 μL。反應(yīng)含50 mM HEPES (pH 7.5), 10 mM MgCl₂, 1 mM EGTA, 1 mM DTT, 0.01% Brij 35, 0.01 mg/mL酪蛋白, 200 μM ATP, 200 μM Polo Box 肽 (NH2-MAGPMQS[pT]PLNGAKK-OH), 和 6 nM 重組 Plk1 (H6-tev-PLK 1-603)。Plk1與0到1×10³ nM GSK461364預(yù)溫育60分鐘。加入2 μM 肽，開(kāi)始反應(yīng)。在23^oC下反應(yīng)15分鐘后, 反應(yīng)淬火，根據(jù)Z′-Lyte建議發(fā)法處理，然后在EnVision酶標(biāo)儀上讀數(shù)。使用底物和產(chǎn)物標(biāo)準(zhǔn)，使原料熒光值轉(zhuǎn)換為形成的產(chǎn)品濃度。隨著與ATP競(jìng)爭(zhēng)性抑制模式相一致的ATP濃度功能變化，則觀察到GSK461364抑制效力發(fā)生變化，測(cè)定GSK461364作用的K_i最大上限值。
細(xì)胞實(shí)驗(yàn)	細(xì)胞系	前列腺(LNCap,PC3),子宮(HeLa),胰臟(ASPC1),肉瘤(Saos-2)，卵巢(OVCAR8),胃(NCI-N87),黑色素瘤(SKMEL3,A431,MALME3M)，結(jié)腸(Colo205,SW620,HCT116),胸腺(SKBR3,MDA-MB-453,MCF7)，肺(NCI-H82,MV522,NCI-H522)等等癌細(xì)胞系
	濃度	10 nM
	孵育時(shí)間	72小時(shí)
	方法	癌細(xì)胞系接種在384孔板上。細(xì)胞在37^oC下溫育24小時(shí)。每孔加入GSK461364，濃度為10 nM。測(cè)定每組細(xì)胞系在T=0的實(shí)驗(yàn)值。72小時(shí)后,從殘留細(xì)胞中抽提含GSK461364或DMSO的培養(yǎng)基，用4',6-二脒基-2-苯基吲哚進(jìn)行核染色,使用 InCell1000 高通量分析儀測(cè)定熒光密度。在72小時(shí)時(shí),計(jì)算每種濃度GSK461364在重復(fù)三次孔的每個(gè)孔中中，4',6-二脒基-2-苯基吲哚染色強(qiáng)度相對(duì)T=0時(shí)強(qiáng)度的百分?jǐn)?shù)。
實(shí)驗(yàn)圖片	檢測(cè)方法	檢測(cè)指標(biāo)	實(shí)驗(yàn)圖片	PMID
實(shí)驗(yàn)圖片	Western blot	p-Myt1 / Myt1 / Plk1		26597303

體內(nèi)研究(In Vivo)
體內(nèi)研究活性	GSK461364作用于培養(yǎng)細(xì)胞的生長(zhǎng)，可以抑制細(xì)胞生長(zhǎng)或產(chǎn)生細(xì)胞毒性，但在適當(dāng)劑量處理下,可以導(dǎo)致移植瘤模型發(fā)生腫瘤衰退。GSK461364 作用于移植瘤模型，具有明顯的抗癌活性。^[1] GSK461364作用于小鼠移植瘤，使細(xì)胞周期停滯，這種作用存在劑量依賴性，與作用于腫瘤生長(zhǎng)相關(guān)。^[2] GSK461364腹腔注射處理不同移植瘤模型，包括Colo205移植瘤，導(dǎo)致衰退或腫瘤生長(zhǎng)延遲。在體內(nèi)，使用GSK461364抑制Plk1，導(dǎo)致有絲分裂停滯，形成由單極或倒塌的有絲分裂紡錘體組成的異常有絲分裂。^[3]
動(dòng)物實(shí)驗(yàn)	Animal Models	攜帶結(jié)腸Colo205移植瘤的裸鼠
	Dosages	25, 50, 和100 mg/kg
	Administration	腹膜注射，每隔2天或4天進(jìn)行。

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
臨床試驗(yàn)信息 (data from https://clinicaltrials.gov, updated on 2024-05-22)
NCT00536835	Completed	Lymphoma Non-Hodgkin	GlaxoSmithKline	August 16 2007	Phase 1

參考文獻(xiàn)
[1] Gilmartin AG, et al. Cancer Res, 2009, 69(17), 6969-6977. [2] Degenhardt Y, et al. Mol Cancer Ther, 2010, 9(7), 2079-2089. [3] Olmos D, et al. Clin Cancer Res, 2011, 17(10), 3420-3430.

參考文獻(xiàn)

[1] Gilmartin AG, et al. Cancer Res, 2009, 69(17), 6969-6977.
[2] Degenhardt Y, et al. Mol Cancer Ther, 2010, 9(7), 2079-2089.
[3] Olmos D, et al. Clin Cancer Res, 2011, 17(10), 3420-3430.

化學(xué)信息&溶解度

分子量	543.6	分子式	C₂₇H₂₈F₃N₅O₂S
CAS號(hào)	929095-18-1	SDF	Download GSK461364 SDF
Smiles	CC(C1=CC=CC=C1C(F)(F)F)OC2=C(SC(=C2)N3C=NC4=C3C=C(C=C4)CN5CCN(CC5)C)C(=O)N
儲(chǔ)存條件(自收到貨起)	3年-20°C粉狀	儲(chǔ)備液保存和期限建議分裝儲(chǔ)備液，避免反復(fù)凍融！	1年-80°C溶于溶劑
儲(chǔ)存條件(自收到貨起)	3年-20°C粉狀	儲(chǔ)備液保存和期限建議分裝儲(chǔ)備液，避免反復(fù)凍融！	1個(gè)月-20°C溶于溶劑

體外溶解度
批次：

Ethanol : 30 mg/mL (55.18 mM)

DMSO : 10 mg/mL ( (18.39 mM) ；DMSO吸濕會(huì)降低化合物溶解度，請(qǐng)使用新開(kāi)封DMSO)

Water : Insoluble

DMSO : 100 mg/mL ( (183.95 mM) ；DMSO吸濕會(huì)降低化合物溶解度，請(qǐng)使用新開(kāi)封DMSO)

Ethanol : 100 mg/mL (183.95 mM)

Water : Insoluble

Ethanol : 100 mg/mL (183.95 mM)

DMSO : 55 mg/mL ( (101.17 mM) ；DMSO吸濕會(huì)降低化合物溶解度，請(qǐng)使用新開(kāi)封DMSO)

Water : Insoluble

摩爾濃度計(jì)算器

體內(nèi)溶解度
批次：

現(xiàn)配現(xiàn)用，請(qǐng)按從左到右的順序依次添加，澄清后再加入下一溶劑

動(dòng)物體內(nèi)配方計(jì)算器

實(shí)驗(yàn)計(jì)算

摩爾濃度計(jì)算器

質(zhì)量	濃度	體積	分子量
=	×	×

稀釋計(jì)算器分子量計(jì)算器

動(dòng)物體內(nèi)配方計(jì)算器（澄清溶液）

第一步：請(qǐng)輸入基本實(shí)驗(yàn)信息（考慮到實(shí)驗(yàn)過(guò)程中的損耗，建議多配一只動(dòng)物的藥量）

給藥劑量 mg/kg 動(dòng)物平均體重 g 每只動(dòng)物給藥體積 μL 動(dòng)物數(shù)量只

第二步：請(qǐng)輸入動(dòng)物體內(nèi)配方組成（配方適用于不溶于水的藥物；不同批次藥物配方比例不同，請(qǐng)聯(lián)系Selleck為您提供正確的澄清溶液配方）

% DMSO + % + % Tween 80 + % ddH2O

%DMSO+ %

計(jì)算結(jié)果：

工作液濃度： mg/ml；

DMSO母液配制方法： mg 藥物溶于μL DMSO溶液（母液濃度mg/mL，注：如該濃度超過(guò)該批次藥物DMSO溶解度，請(qǐng)先聯(lián)系Selleck）；

體內(nèi)配方配制方法：取μL DMSO母液，加入μL PEG300，混勻澄清后加入μL Tween 80，混勻澄清后加入μL ddH₂O，混勻澄清。

體內(nèi)配方配制方法：取μL DMSO母液，加入μL Corn oil，混勻澄清。

注意：1. 首先保證母液是澄清的；
2.一定要按照順序依次將溶劑加入，進(jìn)行下一步操作之前必須保證上一步操作得到的是澄清的溶液，可采用渦旋、超聲或水浴加熱等物理方法助溶。

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常見(jiàn)問(wèn)題及建議解決方法

問(wèn)題 1:
I would like to know whether the recommended in vivo formulation will be suitable for i.p. injections

回答：
GSK461364 in 1% DMSO+30% polyethylene glycol+1% Tween 80 at 30mg/ml is a suspension, and it is fine for oral gavage.

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):

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GSK461364

產(chǎn)品質(zhì)控

GSK461364相關(guān)產(chǎn)品

相關(guān)信號(hào)通路圖

細(xì)胞實(shí)驗(yàn)數(shù)據(jù)示例

生物活性

化學(xué)信息&溶解度

實(shí)驗(yàn)計(jì)算

技術(shù)支持

常見(jiàn)問(wèn)題及建議解決方法