- 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
Quisinostat (JNJ-26481585) 2HCl
Quisinostat (JNJ-26481585) 2HCl是一種新型的，第二代HDAC抑制劑，對(duì)HDAC1最有效，無(wú)細(xì)胞試驗(yàn)中IC50為0.11 nM，作用于HDACs 2，4，10，和11適度有效；比作用于HDACs 3，5，8，和9選擇性強(qiáng)30倍，對(duì)HDACs 6和7作用效果最弱。Phase 2。
Quisinostat (JNJ-26481585) 2HCl Chemical Structure
CAS: 875320-31-3
產(chǎn)品質(zhì)控
批次：
純度：
99.44%
99.44
Quisinostat (JNJ-26481585) 2HCl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
| 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 |
|---|---|---|---|---|---|
| HepG2 | Cell viability assay | 5, 10, 20, 40, 80, 160 and 320 nM | 24, 48, 72 h | The IC50 values of cells for quisinostat treatment at 48 and 72 h were 81.2 and 30.8 nM, respectively. | 28849080 |
| RD cells | Function assay | 15 nM | 24 h and 30 h | GSK690 and JNJ-26481585 cooperated to induce cleavage of the initiator caspase-9 into its active p35 and p37 fragments and of the effector caspase-3 into its active p12 and p17 fragments | 28617441 |
| RH30 cells | Function assay | 15 nM | 24 h and 30 h | GSK690 and JNJ-26481585 cooperated to induce cleavage of the initiator caspase-9 into its active p35 and p37 fragments and of the effector caspase-3 into its active p12 and p17 fragments | 28617441 |
| HuT78 | Function assay | 10 nM | increases the level of acetylated lysine K10 of histone H3 | 30012418 | |
| A549 cells | Cell viability assay | 24, 48, or 72 h | the IC50 values of cells for 48 and 72 h of quisinostat treatment were 82.4 and 42.0 nM, respectively. | 27423454 | |
| HUT78 | Function assay | 18 hrs | Pro-apoptotic activity in human HUT78 cells after 18 hrs by caspase-Glo 3/7 assay, EC50 = 0.0065 μM. | 30122227 | |
| Sf9 | Function assay | Inhibition of full length recombinant human HDAC1 expressed in baculovirus infected Sf9 cells using RHKK-Ac as substrate by fluorescence analysis, IC50 = 0.00011 μM. | 27606546 | ||
| Sf9 | Function assay | Inhibition of full length recombinant human HDAC2 expressed in baculovirus infected Sf9 cells using RHKK-Ac as substrate by fluorescence analysis, IC50 = 0.00033 μM. | 27606546 | ||
| Sf9 | Function assay | Inhibition of full length recombinant human HDAC3/NCOR2 expressed in baculovirus infected Sf9 cells using RHKK-Ac as substrate by fluorescence analysis, IC50 = 0.00486 μM. | 27606546 | ||
| BL21 (DE3) | Function assay | Binding affinity to human His-thioredoxin-tagged HDAC8 expressed in Escherichia coli BL21 (DE3) cells by ITC method, Kd = 0.0227 μM. | 30347148 | ||
| BL21 (DE3) | Function assay | Binding affinity to Schistosoma mansoni His-tagged HDAC8 expressed in Escherichia coli BL21 (DE3) cells by ITC method, Kd = 0.0284 μM. | 30347148 | ||
| BL21 (DE3) | Function assay | Inhibition of human His-thioredoxin-tagged HDAC8 expressed in Escherichia coli BL21 (DE3) cells using Fluor de Lys (R)-HDAC8 as substrate by fluorometric method, IC50 = 0.0644 μM. | 30347148 | ||
| Sf9 | Function assay | Inhibition of full length recombinant human HDAC6 expressed in baculovirus infected Sf9 cells using RHKK-Ac as substrate by fluorescence analysis, IC50 = 0.0768 μM. | 27606546 | ||
| BL21 (DE3) | Function assay | Inhibition of human His-thioredoxin-tagged HDAC8 mL6 mutant expressed in Escherichia coli BL21 (DE3) cells using Fluor de Lys (R)-HDAC8 as substrate by fluorometric method, IC50 = 0.093 μM. | 30347148 | ||
| BL21 (DE3) | Function assay | Inhibition of human His-thioredoxin-tagged HDAC8 mL1/mL6 mutant expressed in Escherichia coli BL21 (DE3) cells using Fluor de Lys (R)-HDAC8 as substrate by fluorometric method, IC50 = 0.094 μM. | 30347148 | ||
| BL21 (DE3) | Function assay | Inhibition of human His-thioredoxin-tagged HDAC8 mL6/L179I mutant expressed in Escherichia coli BL21 (DE3) cells using Fluor de Lys (R)-HDAC8 as substrate by fluorometric method, IC50 = 0.169 μM. | 30347148 | ||
| BL21 (DE3) | Function assay | Inhibition of human His-thioredoxin-tagged HDAC8 mL1/mL6/L179I mutant expressed in Escherichia coli BL21 (DE3) cells using Fluor de Lys (R)-HDAC8 as substrate by fluorometric method, IC50 = 0.217 μM. | 30347148 | ||
| BL21 (DE3) | Function assay | Inhibition of Schistosoma mansoni His-tagged HDAC8 expressed in Escherichia coli BL21 (DE3) cells using Fluor de Lys (R)-HDAC8 as substrate by fluorometric method, IC50 = 0.3034 μM. | 30347148 | ||
| TC32 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 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 | ||
| A673 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells | 29435139 | ||
| DAOY | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY cells | 29435139 | ||
| Saos-2 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 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 | ||
| RD | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD 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 | ||
| BT-12 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-12 cells | 29435139 | ||
| MG 63 (6-TG R) | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for MG 63 (6-TG R) cells | 29435139 | ||
| NB1643 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 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 | ||
| BT-12 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for BT-12 cells | 29435139 | ||
| DAOY | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for DAOY cells | 29435139 | ||
| fibroblast cells | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for control Hh wild type fibroblast 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 | ||
| Rh41 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells | 29435139 | ||
| A673 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for A673 cells) | 29435139 | ||
| Rh30 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh30 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 | ||
| Rh30 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh30 cells | 29435139 | ||
| U-2 OS | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for U-2 OS 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: Orthogonal 3D viability screen for SK-N-SH cells | 29435139 | ||
| Rh41 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh41 cells | 29435139 | ||
| RD | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for RD cells | 29435139 | ||
| Daoy | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Orthogonal 3D viability screen for Daoy cells | 29435139 | ||
| TC32 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Orthogonal 3D viability 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: Orthogonal 3D viability screen for MG 63 (6-TG R) 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 | ||
| Rh18 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh18 cells | 29435139 | ||
| NB1643 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for NB1643 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 | ||
| Rh18 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh18 cells | 29435139 | ||
| Saos-2 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Saos-2 cells | 29435139 | ||
| SJ-GBM2 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Orthogonal 3D viability screen for SJ-GBM2 cells | 29435139 | ||
| RD | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Orthogonal 3D viability screen for RD 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 | Quisinostat (JNJ-26481585) 2HCl是一種新型的，第二代HDAC抑制劑，對(duì)HDAC1最有效，無(wú)細(xì)胞試驗(yàn)中IC50為0.11 nM，作用于HDACs 2，4，10，和11適度有效；比作用于HDACs 3，5，8，和9選擇性強(qiáng)30倍，對(duì)HDACs 6和7作用效果最弱。Phase 2。 | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 特性 | JNJ-26481585是口服生物有效性的，二代氧肟酸基的HDAC抑制劑。 | |||||||||||
| 靶點(diǎn) |
|
| 體外研究(In Vitro) | ||||
| 體外研究活性 | 體外, JNJ-26481585有效抑制一組重組HDAC酶，最有效抑制HDAC1，IC50為 0.11 nM，另外抑制其他家族成員如HDAC2, 4, 10和 11時(shí)效果稍微低點(diǎn)，IC50分別為0.33 nM, 0.64 nM, 0.46 nM 和0.37 nM。[1] JNJ-26481585 作用于實(shí)體瘤和血癌細(xì)胞系，如肺癌，乳腺癌，結(jié)腸癌，前列腺癌，腦癌，和卵巢癌細(xì)胞系，IC50 為3.1 到 246 nM，具有廣譜抗增殖活性，作用于多種人類癌細(xì)胞系時(shí)，JNJ-26481585效果比 R306465, CRA-24781, 和 Mocetinostat 好。[1] 最新研究顯示JNJ-26481585 在低納摩爾濃度時(shí)通過(guò)耗盡Mcl-1及誘導(dǎo)Hsp72產(chǎn)生而促進(jìn)骨髓癌細(xì)胞死亡。[2] |
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|---|---|---|---|---|
| 激酶實(shí)驗(yàn) | HDAC 活性實(shí)驗(yàn) | |||
| 使用桿狀病毒感染的Sf9細(xì)胞表達(dá)全長(zhǎng)HDAC蛋白。此外, HDAC3共表達(dá)作為與人類NCOR2作用的復(fù)合體。為了測(cè)定含HDAC1細(xì)胞復(fù)合體活性, 免疫沉淀反應(yīng)的HDAC1復(fù)合體和組蛋白H4肽段[生物素-(6-氨基)Gly-Ala-(乙?；鵞3H])Lys-Arg-His-Arg-Lys-Val-NH2]的[3H]乙酰基標(biāo)記的片段在50μL酶實(shí)驗(yàn)buffer(25mM HEPES (pH 7.4),1 M 蔗糖, 0.1 mg/mL BSA 和0.01% (v/v) Triton X-100)中溫育。在37oC下溫育45分鐘，或者在室溫下溫育30分鐘。加入底物之前，加入濃度不斷增加的HDAC抑制劑，然后在室溫下預(yù)溫育10分鐘。溫育后，加入35μL 終止 buffer (1 M HCl 和0.4 M 乙酸)終止反應(yīng)。用800μL乙酸乙酯提取釋放 [3H]乙酸，然后通過(guò)閃爍計(jì)數(shù)器量化。通過(guò)Western blot 分析，測(cè)定等量的進(jìn)行免疫沉淀反應(yīng)的HDAC1。 | ||||
| 細(xì)胞實(shí)驗(yàn) | 細(xì)胞系 | NCL-H2106, Colo699和 LNCAP | ||
| 濃度 | 0到300 nM | |||
| 孵育時(shí)間 | 24 小時(shí) | |||
| 方法 | 使用MTT測(cè)定HDAC抑制劑抑制細(xì)胞增殖的效果。使用Alamar Blue法測(cè)定非小細(xì)胞肺癌(NSCLC)細(xì)胞系的增殖。為了測(cè)定 血癌細(xì)胞系的增殖，細(xì)胞溫育72小時(shí)，通過(guò) MTS實(shí)驗(yàn)測(cè)評(píng)毒性。進(jìn)行三次平行實(shí)驗(yàn)，測(cè)定 IC50。 |
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| 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 | HDAC1 / HDAC2 / HDAC4 p21 / CDK2 / CDK4 / CDK6 / Cyclin D1 / Cyclin E1 / Cyclin A2 Caspase-3/ Cleaved caspase-3 / caspase-9 / Cleaved caspase-9 / PARP / Cleaved PARP / Bcl-xl / Bcl2 / Bax / Survivin PI3K-p110 / PI3K-p85 / p-AKT / JNK / p-JNK / p-c-Jun |
|
30443188 | |
| Growth inhibition assay | Cell viability |
|
30443188 | |
| 體內(nèi)研究(In Vivo) | ||
| 體內(nèi)研究活性 | JNJ-26481585按最大耐受劑量(10 mg/kg腹腔注射及40 mg/kg口服處理)作用于對(duì)HDAC1敏感的A2780卵巢癌模型3天，導(dǎo)致產(chǎn)生HDAC1-調(diào)節(jié)的熒光, 可測(cè)的抑制腫瘤生長(zhǎng)效果。JNJ-26481585更有效抑制C170HM2大腸癌肝轉(zhuǎn)移。[1] |
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|---|---|---|
| 動(dòng)物實(shí)驗(yàn) | Animal Models | 在腹股溝區(qū)皮下注射HCT116人類結(jié)腸癌細(xì)胞的雄性NMRI nu/nu無(wú)胸腺鼠, 腹腔注射溶于1 mL 0.9% NaCl(pH 7.3)的C170HM2細(xì)胞懸浮液的雄性MFI裸鼠 |
| Dosages | ≤10 mg/kg | |
| Administration | 口服處理或腹腔注射 | |
| NCT Number | Recruitment | Conditions | Sponsor/Collaborators | Start Date | Phases |
|---|---|---|---|---|---|
| NCT02948075 | Completed | Ovarian Cancer |
NewVac LLC|Janssen Pharmaceutica N.V. Belgium |
September 2015 | Phase 2 |
| NCT01464112 | Completed | Multiple Myeloma |
Janssen Research & Development LLC |
September 16 2011 | Phase 1 |
| NCT00676728 | Terminated | Advanced or Refractory Leukemia|Myelodysplastic Syndromes |
Johnson & Johnson Pharmaceutical Research & Development L.L.C. |
December 2008 | Phase 1 |
| NCT00677105 | Completed | Lymphoma|Neoplasms |
Johnson & Johnson Pharmaceutical Research & Development L.L.C.|Janssen Pharmaceutica N.V. Belgium |
August 2007 | Phase 1 |
化學(xué)信息&溶解度
| 分子量 | 467.39 | 分子式 | C21H28Cl2N6O2 |
| CAS號(hào) | 875320-31-3 | SDF | -- |
| Smiles | CN1C=C(C2=CC=CC=C21)CNCC3CCN(CC3)C4=NC=C(C=N4)C(=O)NO.Cl.Cl | ||
| 儲(chǔ)存條件(自收到貨起) | |||
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體外溶解度 |
DMSO : 79 mg/mL ( (169.02 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 Ethanol : Insoluble |
摩爾濃度計(jì)算器 |
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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(guò)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(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 was thinking of resuspending the powder in 10% hydroxy-propyl-β-cyclodextrin, 25mg/ml mannitol, in sterile water (final pH 8.7). Is this a good vehicle to use? What is the solubility of this chemical in such a vehicle?
回答：
This vehicle can be used for in vivo studies. The following papers also used this vehicle: 1. http://www.nature.com/leu/journal/v23/n10/full/leu2009121a.html; 2. http://cancerres.aacrjournals.org/content/69/13/5307.long (The solvent contains 10% hydroxypropyl-β-cyclodextrin, 0.8% HCl (0.1 N), 0.9 % NaOH (0.1 N), 3.4% mannitol and pyrogen-free water). The solubility is 2mg/ml.
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