- 抑制劑
- 研究領(lǐng)域
- PI3K/Akt/mTOR信號(hào)通路
- 表觀遺傳
- 甲基化
- 免疫&炎癥
- 酪氨酸蛋白激酶
- 血管生成
- 凋亡
- 自噬
- 內(nèi)質(zhì)網(wǎng)應(yīng)激&UPR響應(yīng)
- JAK/STAT信號(hào)通路
- MAPK信號(hào)通路
- 細(xì)胞骨架
- 細(xì)胞周期
- TGF-beta/Smad信號(hào)通路
- DNA損傷/DNA修復(fù)
- 化合物庫(kù)
- 抗體
- 生物試劑
- qPCR
- 2x SYBR Green qPCR Master Mix
- 2x SYBR Green qPCR Master Mix(Low ROX)
- 2x SYBR Green qPCR Master Mix(High ROX)
- 蛋白實(shí)驗(yàn)
- Protein A/G免疫沉淀磁珠
- Anti-DYKDDDDK Tag免疫磁珠
- Anti-DYKDDDDK Tag親和凝膠
- Anti-Myc免疫磁珠
- Anti-HA免疫磁珠
- 磁力架
- Poly DYKDDDDK Tag多肽
- 蛋白酶抑制劑Cocktail
- 蛋白酶抑制劑Cocktail(DMSO儲(chǔ)液)
- 磷酸酶抑制劑Cocktail
- 細(xì)胞實(shí)驗(yàn)
- Cell Counting Kit-8 (CCK-8)
- 動(dòng)物實(shí)驗(yàn)
- 鼠尾直接PCR試劑盒(快速基因型鑒定)
- 小鼠CD3+ T細(xì)胞分選試劑盒
- 小鼠CD4+ T細(xì)胞分選試劑盒
- 小鼠CD8+ T細(xì)胞分選試劑盒
- 新產(chǎn)品
- 聯(lián)系我們
Adavosertib (MK-1775)
別名: AZD1775
Adavosertib (MK-1775, AZD1775)是一種有效的，高選擇性Wee1抑制劑，無細(xì)胞試驗(yàn)中IC50為5.2 nM；阻礙G2期DNA損傷檢驗(yàn)點(diǎn)。Phase 2。
Adavosertib (MK-1775) Chemical Structure
CAS: 955365-80-7
產(chǎn)品質(zhì)控
批次：
純度：
99.99%
99.99
Adavosertib (MK-1775)相關(guān)產(chǎn)品
| 相關(guān)產(chǎn)品 | PD0166285 | 點(diǎn)擊展開 |
|---|---|---|
| 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 |
相關(guān)信號(hào)通路圖
細(xì)胞實(shí)驗(yàn)數(shù)據(jù)示例
| 細(xì)胞系 | 實(shí)驗(yàn)類型 | 給藥濃度 | 孵育時(shí)間 | 活性描述 | 文獻(xiàn)信息 |
|---|---|---|---|---|---|
| CMY | Cell Viability Assay | 10-10000 nM | 72 h | reduces cell vialibity in a concentration-dependent manner | 24962331 |
| CMK | Cell Viability Assay | 10-10000 nM | 72 h | reduces cell vialibity in a concentration-dependent manner | 24962331 |
| MOLM-13 | Growth Inhibition Assay | 125/250/500 nM | 48 h | increases cell death in a concentration-dependent manner | 25084614 |
| OCI-AML3 | Growth Inhibition Assay | 125/250/500 nM | 48 h | increases cell death in a concentration-dependent manner | 25084614 |
| HL-60 | Growth Inhibition Assay | 125/250/500 nM | 48 h | increases cell death in a concentration-dependent manner | 25084614 |
| U937 | Growth Inhibition Assay | 125/250/500 nM | 48 h | increases cell death in a concentration-dependent manner | 25084614 |
| MV4-11 | Growth Inhibition Assay | 125/250/500 nM | 48 h | increases cell death in a concentration-dependent manner | 25084614 |
| THP-1 | Growth Inhibition Assay | 125/250/500 nM | 48 h | increases cell death in a concentration-dependent manner | 25084614 |
| SK-N-DZ | Apoptosis Assay | 500 nM | 48 h | induces cell apoptosis | 25308916 |
| SK-N-AS | Apoptosis Assay | 500 nM | 48 h | induces cell apoptosis | 25308916 |
| IST-MES1 | Cell Viability Assay | 150/250 nM | 72 h | enhances the cisplatin cytotoxic effect in a concentration-dependent manner | 24365782 |
| IST-MES2 | Cell Viability Assay | 150/250 nM | 72 h | enhances the cisplatin cytotoxic effect in a concentration-dependent manner | 24365782 |
| REN | Cell Viability Assay | 150/250 nM | 72 h | enhances the cisplatin cytotoxic effect in a concentration-dependent manner | 24365782 |
| NCI-H2452 | Cell Viability Assay | 150/250 nM | 72 h | enhances the cisplatin cytotoxic effect in a concentration-dependent manner | 24365782 |
| MSTO-211H | Cell Viability Assay | 150/250 nM | 72 h | enhances the cisplatin cytotoxic effect in a concentration-dependent manner | 24365782 |
| NCI-H2052 | Cell Viability Assay | 150/250 nM | 72 h | enhances the cisplatin cytotoxic effect in a concentration-dependent manner | 24365782 |
| T98G? | Apoptosis Assay | 100/250 nM | 6 h | enhances radiation-induced cell killing | 21992793 |
| A549 | Apoptosis Assay | 200 nM | 1 h | radiosensitizes NSCLC cells in a p53-dependent manner | 21799033 |
| H460 | Apoptosis Assay | 200 nM | 1 h | radiosensitizes NSCLC cells in a p53-dependent manner | 21799033 |
| H1299 | Apoptosis Assay | 200 nM | 1 h | radiosensitizes NSCLC cells in a p53-dependent manner | 21799033 |
| Calu-6? | Apoptosis Assay | 200 nM | 1 h | radiosensitizes NSCLC cells in a p53-dependent manner | 21799033 |
| WiDr | Kinase Assays | 10-10000 nM | 8 h | inhibits phosphorylation of CDC2 at Tyr15 with an EC50?value of 85 nmol/L pretreated with gemcitabine | 19887545 |
| Function assay | MDA-MB-231 | 0.1 to 10 uM | 6 hrs | Inhibition of Wee1 in human MDA-MB-231 cells assessed as decrease in CDK1 phosphorylation at Tyr 15 at 0.1 to 10 uM after 6 hrs by Western blot method | 28792760 |
| Function assay | HEK293T | 0.1 to 10 uM | 6 hrs | Inhibition of Wee1 in HEK293T cells assessed as decrease in CDK1 phosphorylation at Tyr15 at 0.1 to 10 uM after 6 hrs by Western blot method | 28792760 |
| Function assay | HEK293T | 0.1 to 10 uM | 6 hrs | Inhibition of PLK1 in HEK293T cells assessed as decrease in TCTP phosphorylation at 0.1 to 10 uM after 6 hrs by Western blot method | 28792760 |
| Function assay | MDA-MB-23 | 0.1 to 10 uM | 6 hrs | Inhibition of PLK1 in human MDA-MB-23 cells assessed as decrease in TCTP phosphorylation at 0.1 to 10 uM after 6 hrs by Western blot method | 28792760 |
| Antiproliferative assay | MDA-MB-231 | 72 hrs | Antiproliferative activity against human MDA-MB-231 cells measured after 72 hrs by CellTiter-Blue assay, IC50 = 0.26 μM. | 28792760 | |
| Antiproliferative assay | HEK293T | 72 hrs | Antiproliferative activity against HEK293T cells measured after 72 hrs by CellTiter-Blue assay, IC50 = 0.29 μM. | 28792760 | |
| Antiproliferative assay | MM1S | 72 hrs | Antiproliferative activity against human MM1S cells measured after 72 hrs by CellTiter-Blue assay, IC50 = 0.31 μM. | 28792760 | |
| Function assay | HEK293 | 1 hr | Inhibition of human full length PKMYT1 expressed in HEK293 cells using EFS (247 to 259 residues) as substrate after 1 hr by fluorescence polarization immunoasay, Ki = 0.47 μM. | 29941193 | |
| Function assay | HEK293 | 1 hr | Inhibition of human full length PKMYT1 expressed in HEK293 cells using EFS (247 to 259 residues) as substrate after 1 hr by fluorescence polarization immunoasay, IC50 = 4.94 μM. | 29941193 | |
| Dayo | Growth Inhibition Assay | IC50=150 nM | 24661910 | ||
| SK-N-DZ | Growth Inhibition Assay | IC50=0.36?±?0.01 μM | 25308916 | ||
| SK-N-AS | Growth Inhibition Assay | IC50=0.50?±?0.02 μM | 25308916 | ||
| SK-N-BE (2), MK→PAN | Growth Inhibition Assay | IC50=2.4?±?0.3 μM | 25308916 | ||
| SK-N-BE (2), PAN→MK | Growth Inhibition Assay | IC50=26.6?±?9.6 μM | 25308916 | ||
| SK-N-BE (2) | Growth Inhibition Assay | IC50=2.4?±?0.3 μM | 25308916 | ||
| PANC-1 | Growth Inhibition Assay | IC50=10.6 ± 1.1 μM | 25458954 | ||
| MIAPaCa-2 | Growth Inhibition Assay | IC50=0.5 ± 0.05 μM | 25458954 | ||
| HPAC | Growth Inhibition Assay | IC50=0.5 ± 0.01 μM | 25458954 | ||
| CFPAC-1 | Growth Inhibition Assay | IC50=3.3 ± 0.2 μM | 25458954 | ||
| BxPC-3 | Growth Inhibition Assay | IC50=0.8 ± 0.03 μM | 25458954 | ||
| ASPC-1 | Growth Inhibition Assay | IC50=13.2 ± 1.1 μM | 25458954 | ||
| UW228 | Growth Inhibition Assay | IC50=232 nM | 24661910 | ||
| WEE1 | Growth Inhibition Assay | IC50=5.2 nM | 23699655 | ||
| CDC2 | Growth Inhibition Assay | IC50＞1000 nM | 23699655 | ||
| CDK7 | Growth Inhibition Assay | IC50＞1000 nM | 23699655 | ||
| MYT1 | Growth Inhibition Assay | IC50=530 nM | 23699655 | ||
| Function assay | Expi293F | Binding affinity to recombinant human full-length N-terminal His8-tagged Wee1 (1 to 646 residues) expressed in human Expi293F cells assessed as dessociation constant by quantitative real-time PCR method, Kd = 0.0032 μM. | 28792760 | ||
| Function assay | Expi293F | Binding affinity to recombinant human full-length N-terminal His8-tagged Wee2 (1 to 567 residues) expressed in human Expi293F cells assessed as dessociation constant by quantitative real-time PCR method, Kd = 0.0039 μM. | 28792760 | ||
| qHTS assay | TC32 | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 cells | 29435139 | ||
| qHTS assay | U-2 OS | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for U-2 OS cells | 29435139 | ||
| qHTS assay | A673 | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells | 29435139 | ||
| qHTS assay | DAOY | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY cells | 29435139 | ||
| qHTS assay | Saos-2 | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 cells | 29435139 | ||
| qHTS assay | BT-37 | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 cells | 29435139 | ||
| qHTS assay | RD | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells | 29435139 | ||
| qHTS assay | SK-N-SH | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH cells | 29435139 | ||
| qHTS assay | BT-12 | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-12 cells | 29435139 | ||
| qHTS assay | NB1643 | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells | 29435139 | ||
| qHTS assay | OHS-50 | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells | 29435139 | ||
| qHTS assay | BT-12 | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for BT-12 cells | 29435139 | ||
| qHTS assay | DAOY | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for DAOY cells | 29435139 | ||
| qHTS assay | SK-N-SH | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SK-N-SH cells | 29435139 | ||
| qHTS assay | Rh41 | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells | 29435139 | ||
| qHTS assay | A673 | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for A673 cells) | 29435139 | ||
| qHTS assay | MG 63 (6-TG R) | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for MG 63 (6-TG R) cells | 29435139 | ||
| qHTS assay | U-2 OS | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for U-2 OS cells | 29435139 | ||
| qHTS assay | OHS-50 | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for OHS-50 cells | 29435139 | ||
| qHTS assay | Rh41 | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh41 cells | 29435139 | ||
| qHTS assay | RD | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for RD cells | 29435139 | ||
| qHTS assay | SJ-GBM2 | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells | 29435139 | ||
| qHTS assay | SK-N-MC | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells | 29435139 | ||
| qHTS assay | NB-EBc1 | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells | 29435139 | ||
| qHTS assay | LAN-5 | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells | 29435139 | ||
| qHTS assay | Rh18 | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh18 cells | 29435139 | ||
| qHTS assay | SJ-GBM2 | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SJ-GBM2 cells | 29435139 | ||
| qHTS assay | Saos-2 | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Saos-2 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 | Adavosertib (MK-1775, AZD1775)是一種有效的，高選擇性Wee1抑制劑，無細(xì)胞試驗(yàn)中IC50為5.2 nM；阻礙G2期DNA損傷檢驗(yàn)點(diǎn)。Phase 2。 | ||
|---|---|---|---|
| 特性 | 首個(gè)報(bào)道的 Wee1抑制劑。 | ||
| 靶點(diǎn) |
|
| 體外研究(In Vitro) | ||||
| 體外研究活性 | MK-1775以ATP競(jìng)爭(zhēng)的方式抑制Wee1激酶。與作用于Wee1相比，MK-1775對(duì)Yes的效能低2-到3-倍，IC50為14 nM，對(duì)7種其他激酶的效能低10倍，1 μM濃度下抑制率>80%，比對(duì)人Myt 1選擇性高100倍以上，并抑制周期蛋白依賴性激酶1 (CDC2) 在可選擇位點(diǎn)(Thr14) 的磷酸化作用。通過阻斷負(fù)荷突變型p53的WiDr細(xì)胞中Wee1活性，廢止DNA損傷檢控點(diǎn)，MK-1775治療抑制Tyr15 (CDC2Y15)位點(diǎn)的CDC2基礎(chǔ)磷酸化作用，EC50為49 nM，并劑量依賴性抑制誘導(dǎo)的CDC2磷酸化和細(xì)胞周期阻滯，EC50分別為82 nM和81 nM，180 nM 和163 nM，以及159 nM 和 160 nM。30-100 nM 的MK-1775單獨(dú)治療在WiDr 和 H1299細(xì)胞中沒有顯著的抗增殖作用，而300 nM的MK-1775足以抑制>80%的Wee1，表現(xiàn)出溫和但顯著的抗增殖作用，在WiDr和H1299細(xì)胞中抑制率分別為34.1%和28.4%。[1] |
|||
|---|---|---|---|---|
| 激酶實(shí)驗(yàn) | 體外激酶試驗(yàn) | |||
| 使用重組人Wee1。激酶反應(yīng)使用10 μM ATP，1.0 μCi of [γ-33P]ATP，和2.5 μg poly(Lys, Tyr)作為底物，在逐漸增加濃度的MK-1775存在下，在30°C環(huán)境中進(jìn)行30分鐘。整合到底物的放射性被捕獲到MultiScreen-PH平板，在液體閃爍計(jì)數(shù)器上計(jì)數(shù)。 | ||||
| 細(xì)胞實(shí)驗(yàn) | 細(xì)胞系 | WiDr，NCI-H1299，TOV21G，和 HeLa細(xì)胞 | ||
| 濃度 | 在DMSO中溶解，終濃度為~10 μM | |||
| 孵育時(shí)間 | 24小時(shí) | |||
| 方法 | 細(xì)胞處理24小時(shí)，然后用MK-1775再處理24小時(shí)。細(xì)胞活性使用SpectraMax通過WST-8試劑盒測(cè)定。細(xì)胞內(nèi)caspase-3/7活性使用Caspase-3/7 Glo試劑盒測(cè)定。 |
|||
| 實(shí)驗(yàn)圖片 | 檢測(cè)方法 | 檢測(cè)指標(biāo) | 實(shí)驗(yàn)圖片 | PMID |
| Western blot | p-Cdk1(Y15) / Cdk1 p-KAP1(S824) / p-Chk2(T68) / p-Chk1(S345) PARP / CF-PARP / pH3(S10) / p-CDC25c(S216) / p-CDK2(Y15) WEE1 |
|
25609063 | |
| Immunofluorescence | tubulin / p-HH3(S10) γH2AX Cleaved caspase-3 / pH3 |
|
30755439 | |
| Growth inhibition assay | Cell viability IC50 |
|
25458954 | |
| 體內(nèi)研究(In Vivo) | ||
| 體內(nèi)研究活性 | MK-1775(~20 mg/kg)單獨(dú)治療對(duì)WiDr異種移植物表現(xiàn)出最小的抗腫瘤作用，在大鼠體內(nèi)第3天時(shí)T/C為69%。在裸鼠HeLa-luc和TOV21G-shp53異種移植模型中，MK-1775單獨(dú)的抗腫瘤效能是溫和的。[1] |
|
|---|---|---|
| 動(dòng)物實(shí)驗(yàn) | Animal Models | 負(fù)荷WiDr，HeLa-luc，或TOV21G-shp53腫瘤的免疫缺陷裸鼠(F344/NJcl-rnu) |
| Dosages | ~20 mg/kg/day | |
| Administration | 口服 | |
| NCT Number | Recruitment | Conditions | Sponsor/Collaborators | Start Date | Phases |
|---|---|---|---|---|---|
| NCT03253679 | Completed | Advanced Malignant Solid Neoplasm|Refractory Malignant Solid Neoplasm |
National Cancer Institute (NCI) |
January 16 2019 | Phase 2 |
| NCT03668340 | Active not recruiting | Uterine Cancer |
Dana-Farber Cancer Institute|AstraZeneca |
October 22 2018 | Phase 2 |
| NCT03028766 | Completed | Hypopharynx Squamous Cell Carcinoma|Oral Cavity Squamous Cell Carcinoma|Larynx Cancer |
University of Birmingham|AstraZeneca|Cancer Research UK |
June 22 2017 | Phase 1 |
化學(xué)信息&溶解度
| 分子量 | 500.6 | 分子式 | C27H32N8O2 |
| CAS號(hào) | 955365-80-7 | SDF | Download Adavosertib (MK-1775) SDF |
| Smiles | CC(C)(C1=NC(=CC=C1)N2C3=NC(=NC=C3C(=O)N2CC=C)NC4=CC=C(C=C4)N5CCN(CC5)C)O | ||
| 儲(chǔ)存條件(自收到貨起) | |||
|
體外溶解度 |
DMSO : 100 mg/mL ( (199.76 mM) ；DMSO吸濕會(huì)降低化合物溶解度，請(qǐng)使用新開封DMSO) Water : Insoluble Ethanol : Insoluble |
摩爾濃度計(jì)算器 |
|
體內(nèi)溶解度 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
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)過程中的損耗，建議多配一只動(dòng)物的藥量）
mg/kg
g
μL
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。
技術(shù)支持
在訂購(gòu)、運(yùn)輸、儲(chǔ)存和使用我們的產(chǎn)品的任何階段，您遇到的任何問題，均可以通過撥打我們的熱線電話400-668-6834，或者技術(shù)支持郵箱tech@selleck.cn，直接聯(lián)系到我們。我們會(huì)在24小時(shí)內(nèi)盡快聯(lián)系您。
如果有其他問題，請(qǐng)給我們留言。
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常見問題及建議解決方法
問題 1:
How to prepare MK1775 methylcellulose solution? and how to prepare methylcellulose itself? Once make the MK1775 methylcellulose solution, how should i keep it?
回答：
MK1775 in 0.5% methylcellulose is a suspension or emulsion, and it is ok to treat mice orally. It is recommended to dissolve methylcellulose in saline. It will take some time to dissolve methylcellulose, and you can vortex it for a while. The MK1775 methylcellulose solution can be stored at 4°C for a week.
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