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PHA-767491鹽酸鹽

NMR下載 COA and HPLC MSDS下載
names：
PHA-767491 hydrochloride
CAS號(hào)：
942425-68-5
MDL Number： MFCD11519962
MF(分子式)： C12H12ClN3O MW(分子量)： 249.7
EINECS: Reaxys Number:
Pubchem ID:11715766 Brand:BIOFOUNT

PHA-767491鹽酸鹽(942425-68-5,PHA-767491 hydrochloride,CAY-10572 hydrochloride)是一種有效的，具有ATP競爭性的雙重Cdc7 / Cdk9抑制劑，可防止DNA復(fù)制的開始。它在多種人類細(xì)胞系中抑制細(xì)胞增殖，并在體內(nèi)以p53獨(dú)立的方式誘導(dǎo)細(xì)胞凋亡。它還抑制有絲分裂原激活的蛋白激酶激活的蛋白激酶2（MK2）。

貨品編碼	規(guī)格	純度	價(jià)格 (￥)	現(xiàn)價(jià)(￥)	特價(jià)(￥)	庫存描述	數(shù)量	總計(jì) (￥)
YZM001253-50mg	50mg	99.91%	￥ 2761.00	￥ 2761.00		2-3天	- +	￥ 0.00
YZM001253-10mg	10mg	99.91%	￥ 646.43	￥ 646.43		2-3天	- +	￥ 0.00

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中文別名	PHA-767491鹽酸鹽(942425-68-5); CAY-10572鹽酸鹽；PHA-767491鹽酸鹽；CAY 10572鹽酸鹽；PHA 767491鹽酸鹽；CAY10572鹽酸鹽；PHA767491鹽酸鹽;
英文別名	PHA-767491 hydrochloride(942425-68-5);CAY-10572 hydrochloride; PHA-767491 hydrochloride; CAY 10572 hydrochloride; PHA 767491 hydrochloride; CAY10572 hydrochloride; PHA767491 hydrochloride;
CAS號(hào)	942425-68-5
Inchi	InChI=1S/C12H11N3O.ClH/c16-12-9-7-11(8-1-4-13-5-2-8)15-10(9)3-6-14-12;/h1-2,4-5,7,15H,3,6H2,(H,14,16);1H
InchiKey	IMVNFURYBZMFDZ-UHFFFAOYSA-N
分子式 Formula	C12H12ClN3O
分子量 Molecular Weight	249.7
溶解度Solubility	生物體外In Vitro:H2O : 50 mg/mL(200.24 mM;Need ultrasonic)DMSO溶解度17.33 mg/mL(69.40 mM;Need ultrasonic and warming)
性狀	固體粉末,Power
儲(chǔ)藏條件 Storage conditions	-20°C 3 years年 4°C 2 years年 / In solvent溶液中:-80°C 6 months月 -20°C 1 month月

PHA-767491鹽酸鹽(942425-68-5,PHA-767491 hydrochloride,CAY-10572 hydrochloride)實(shí)驗(yàn)注意事項(xiàng)：
1.實(shí)驗(yàn)前需戴好防護(hù)眼鏡，穿戴防護(hù)服和口罩，佩戴手套，避免與皮膚接觸。
2.實(shí)驗(yàn)過程中如遇到有毒或者刺激性物質(zhì)及有害物質(zhì)產(chǎn)生，必要時(shí)實(shí)驗(yàn)操作需要手套箱內(nèi)完成以免對實(shí)驗(yàn)人員造成傷害
3.實(shí)驗(yàn)后產(chǎn)生的廢棄物需分類存儲(chǔ)，并交于專業(yè)生物廢氣物處理公司處理，以免造成環(huán)境污染Experimental considerations:
1. Wear protective glasses, protective clothing and masks, gloves, and avoid contact with the skin during the experiment.
2. The waste generated after the experiment needs to be stored separately, and handed over to a professional biological waste gas treatment company to avoid environmental pollution.

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產(chǎn)品說明	PHA-767491鹽酸鹽(942425-68-5,PHA-767491 hydrochloride,CAY-10572 hydrochloride)是一種有效的Cdc7-Dbf4(DDK)/Cdk9的雙重的抑制劑
Introduction	PHA-767491鹽酸鹽(942425-68-5,PHA-767491 hydrochloride,CAY-10572 hydrochloride)is a dualCdc7/Cdk9inhibitor, withIC50s of 10 nM and 34 nM, respectively.
Application1	PHA-767491 hydrochloride 是一種 Cdc7-Dbf4 (DDK)/Cdk9 的雙重抑制劑，IC50 值分別為 10 nM 和 34 nM。
Application2	ATP競爭性強(qiáng)的雙重cdc7 / cdk9抑制劑（IC50值分別為10和34 nM），可防止DNA復(fù)制的啟動(dòng)。在體內(nèi)抑制多種人類細(xì)胞系（IC50?0.86- 5.87 muM）中的細(xì)胞增殖，并誘導(dǎo)細(xì)胞凋亡。還抑制促分裂原激活的蛋白激酶激活的蛋白激酶2（MK2）（IC50 = 171 nM）。
Application3

PHA-767491鹽酸鹽(942425-68-5,PHA-767491 hydrochloride,CAY-10572 hydrochloride)藥理學(xué)：

PHA-767491鹽酸鹽是一種有效的，具有ATP競爭性的雙重Cdc7 / Cdk9抑制劑，可防止DNA復(fù)制的開始。它在多種人類細(xì)胞系中抑制細(xì)胞增殖，并在體內(nèi)以p53獨(dú)立的方式誘導(dǎo)細(xì)胞凋亡。它還抑制有絲分裂原激活的蛋白激酶激活的蛋白激酶2（MK2）。

警示圖
危險(xiǎn)性	warning
危險(xiǎn)性警示	Not available
安全聲明	H303吞入可能有害+H313皮膚接觸可能有害+H2413吸入可能對身體有害
安全防護(hù)	P264處理后徹底清洗+P280戴防護(hù)手套/穿防護(hù)服/戴防護(hù)眼罩/戴防護(hù)面具+P305如果進(jìn)入眼睛+P351用水小心沖洗幾分鐘+P338取出隱形眼鏡（如果有）并且易于操作,繼續(xù)沖洗+P337如果眼睛刺激持續(xù)+P2393獲得醫(yī)療建議/護(hù)理
備注	實(shí)驗(yàn)過程中防止吸入、食入，做好安全防護(hù)

Sasi NK, et al. The potent Cdc7-Dbf4 (DDK) kinase inhibitor XL413 has limited activity in many cancer cell lines and discovery of potential new DDK inhibitor scaffolds. PLoS One. 2014 Nov 20;9(11):e11

Li W, et al. Dual Inhibition of Cdc7 and Cdk9 by PHA-767491 Suppresses Hepatocarcinoma Synergistically with 5-Fluorouracil. Curr Cancer Drug Targets. 2015;15(3):196-204.

Erbayraktar Z, et al. Cell division cycle 7-kinase inhibitor PHA-767491 hydrochloride suppresses glioblastoma growth and invasiveness. Cancer Cell Int. 2016 Nov 18;16:88.

Montagnoli A, et al. A Cdc7 kinase inhibitor restricts initiation of DNA replication and has antitumor activity. Nat Chem Biol. 2008 Jun;4(6):357-65.

PHA-767491鹽酸鹽(942425-68-5,PHA-767491 hydrochloride,CAY-10572 hydrochloride)參考文獻(xiàn)：

1、Structure-function study of a novel inhibitor of the casein kinase 1 family in Arabidopsis thaliana
Ami N Saito 1, Hiromi Matsuo 2, Keiko Kuwata 2, Azusa Ono 3, Toshinori Kinoshita 2 3, Junichiro Yamaguchi 1, Norihito Nakamich

Abstract Casein kinase 1 (CK1) is an evolutionarily conserved protein kinase family among eukaryotes. Studies in non-plants have shown CK1-dependent divergent biological processes, but the collective knowledge regarding the biological roles of plant CK1 lags far behind other members of the Eukarya. One reason for this is that plants have many more genes encoding CK1 than do animals. To accelerate our understanding of the plant CK1 family, a strong CK1 inhibitor that efficiently inhibits multiple members of the CK1 protein family in vivo (i.e., in planta) is required. Here, we report a novel, specific, and effective CK1 inhibitor in Arabidopsis. Using circadian period-lengthening activity as an estimation of the CK1 inhibitor effect in vivo, we performed a structure-activity relationship study of analogues of the CK1 inhibitor PHA767491 (1,5,6,7-tetrahydro-2-(4-pyridinyl)-4H-pyrrolo[3,2-c]pyridin-4-one hydrochloride). A propargyl group at the pyrrole nitrogen atom (AMI-212) or a bromine atom at the pyrrole C3 position (AMI-23) had stronger CK1 inhibitory activity than PHA767491. A hybrid molecule of AMI-212 and AMI-23 (AMI-331) was about 100-fold more inhibitory than the parent molecule PHA767491. Affinity proteomics using an AMI-331 probe showed that the targets of AMI-331 inhibition are mostly CK1 kinases. As such, AMI-331 is a potent and selective CK1 inhibitor that shows promise in the research of CK1 in plants.

2、Cell division cycle 7-kinase inhibitor PHA-767491 hydrochloride suppresses glioblastoma growth and invasiveness
Zubeyde Erbayraktar # 1, Begum Alural # 2 3, Resat Serhat Erbayraktar 4, Erdogan Pekcan Erkan

Abstract Background: Genomic instability is a hallmark of cancer cells, and this cellular phenomenon can emerge as a result of replicative stress. It is possible to take advantage of replicative stress, and enhance it in a targeted way to fight cancer cells. One of such strategies involves targeting the cell division cycle 7-related protein kinase (CDC7), a protein with key roles in regulation of initiation of DNA replication. CDC7 overexpression is present in different cancers, and small molecule inhibitors of the CDC7 have well-documented anti-tumor effects. Here, we aimed to test the potential of CDC7 inhibition as a new strategy for glioblastoma treatment. Methods: PHA-767491 hydrochloride was used as the CDC7 inhibitor. Two glioblastoma cell lines (U87-MG and U251-MG) and a control cell line (3T3) were used to characterize the effects of CDC7 inhibition. The effect of CDC7 inhibition on cell viability, cell proliferation, apoptosis, migration, and invasion were analyzed. In addition, real-time PCR arrays were used to identify the differentially expressed genes in response to CDC7 inhibition. Results: Our results showed that CDC7 inhibition reduces glioblastoma cell viability, suppresses cell proliferation, and triggers apoptosis in glioblastoma cell lines. In addition, we determined that CDC7 inhibition also suppresses glioblastoma cell migration and invasion. To identify molecular targets of CDC7 inhibition, we used real-time PCR arrays, which showed dysregulation of several mRNAs and miRNAs. Conclusions: Taken together, our findings suggest that CDC7 inhibition is a promising strategy for treatment of glioblastoma.

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