Barasertib (AZD1152-HQPA)

Barasertib (AZD1152-HQPA)は一種の高度選択性のオーロラ B阻害剤で、無細胞試験でIC50値が0.37 nMです。Barasertib (AZD1152-HQPA)はオーロラ Bに作用する選択性はオーロラAに作用する選択性より3700左右倍が高くなります。臨床1期。

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Barasertib (AZD1152-HQPA) 化学構造
分子量: 507.56

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製品説明

  • Compare Aurora Kinase Inhibitors
    Aurora Kinase製品生物活性の比較
  • 研究分野
  • Combination Therapy
    併用療法

製品の説明

生物活性

製品説明 Barasertib (AZD1152-HQPA)は一種の高度選択性のオーロラ B阻害剤で、無細胞試験でIC50値が0.37 nMです。Barasertib (AZD1152-HQPA)はオーロラ Bに作用する選択性はオーロラAに作用する選択性より3700左右倍が高くなります。臨床1期。
ターゲット Aurora B
IC50 0.37 nM [1]
In vitro試験 AZD1152 displays >3000-fold selectivity for Aurora B as compared with Aurora A which has an IC50 of 1.368 μM. AZD1152 has even less activity against 50 other serine-threonine and tyrosine kinases including FLT3, JAK2, and Abl. AZD1152 inhibits the proliferation of hematopoietic malignant cells such as HL-60, NB4, MOLM13, PALL-1, PALL-2, MV4-11, EOL-1, THP-1, and K562 cells with IC50 of 3-40 nM, displaying ~100-fold potency than another Aurora kinase inhibitor ZM334739 which has IC50 of 3-30 μM. AZD1152 inhibits the clonogenic growth of MOLM13 and MV4-11 cells with IC50 of 1 nM and 2.8 nM, respectively, as well as the freshly isolated imatinib-resistant leukemia cells with IC50 values of 1-3 nM, more significantly compared with bone marrow mononuclear cells with IC50 values of >10 nM. AZD1152 induces accumulation of cells with 4N/8N DNA content, followed by apoptosis in a dose- and time-dependent manner. [1]
Cell Data
Cell LinesAssay TypeConcentrationIncubation TimeFormulationActivity DescriptionPMID
LNCaP NUf0VXU4T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M{nHZ|AuPTByIH7N MVi0POKhcA>? M{TzbWlEPTB;MkWgcm0> MonLNlUzPzd4NUm=
LNCaP MVTBdI9xfG:|aYOgRZN{[Xl? NVPlZmpIOC13MECgcm0> M4P2R|Q5yqCq NGXHTGtqdmS3Y3XzJIFxd3C2b4TpZ{Bk\WyuIHTlZZRpKHSqcn;1[4gh[2G|cHHz[U0{KHWycnXneYxifGmxbh?= Mm\6NlUzPzd4NUm=
LNCaP MYPGeY5kfGmxbjDBd5NigQ>? MVu1NEBvVQ>? NWfWVXhQPDhiaB?= NFG3eHBqdmS3Y3XzJI1q[3KxboXjcIVqKHerdHigZY5mfWenbnnjJI1m[2ijbnnzcS=> M3fGSFI2Ojd5NkW5
Ramos M1fod2Z2dmO2aX;uJGF{e2G7 MUK1NFAhdk1? NFzVOVIxNTd{IHi= NYPFb3pVcW6qaXLpeJMhSXW{b4LhJGIhc2mwYYPl MV[yNVM4OTR2Nh?=
Daudi  NVPJVGhxTnWwY4Tpc44hSXO|YYm= NHvjfZo2ODBibl2= M3nO[lAuPzJiaB?= NVu3ZYIxcW6qaXLpeJMhSXW{b4LhJGIhc2mwYYPl MkWzNlE{PzF2NE[=
L540 NWXjdXU5TnWwY4Tpc44hSXO|YYm= NULWO3hbPTByIH7N NFyxdokxNTd{IHi= NWTZW5ZMcW6qaXLpeJMhSXW{b4LhJGIhc2mwYYPl M1yxS|IyOzdzNES2
BJAJ NFzJTmJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWG1NFAhdk1? NUC0PZVTOC15MjDo MmqzbY5pcWKrdIOgZ4VtdCCpcn;3eIghe2mpbnnmbYNidnSueR?= MYeyNVM4OTR2Nh?=
Ramos NEnje25Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFzhOG02ODBibl2= M17Ne|AuPzJiaB?= MULpcohq[mm2czDj[YxtKGe{b4f0bEB{cWewaX\pZ4FvfGy7 M4fYRVIyOzdzNES2
Raji NVr1NohST3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXS1NFAhdk1? NULyXItXOC15MjDo NEPDdJJqdmirYnn0d{Bk\WyuIHfyc5d1cCC|aXfubYZq[2GwdHz5 M1H2SVIyOzdzNES2
Daudi  MlOzS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NX7TOFJ5PTByIH7N M1HCOlAuPzJiaB?= MVfpcohq[mm2czDj[YxtKGe{b4f0bEB{cWewaX\pZ4FvfGy7 MWGyNVM4OTR2Nh?=
L428 M3zmUWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MoHEOVAxKG6P NXfzSYN{OC15MjDo M1zhSolvcGmkaYTzJINmdGxiZ4Lve5Rp M4nVe|IyOzdzNES2
KM-H2 MWDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFr3TGE2ODBibl2= MnjLNE04OiCq NUXIOoh[cW6qaXLpeJMh[2WubDDndo94fGh? MluxNlE{PzF2NE[=
HDLM-2 M4XIWmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mmf4OVAxKG6P M3HKU|AuPzJiaB?= MkXUbY5pcWKrdIOgZ4VtdCCpcn;3eIg> NHTRSWkzOTN5MUS0Oi=>
L450 M2fjfWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NYSxfllMPTByIH7N M{DYZVAuPzJiaB?= MoXBbY5pcWKrdIOgZ4VtdCCpcn;3eIg> MVOyNVM4OTR2Nh?=
BJAJ NX2wbXhDSXCxcITvd4l{KEG|c3H5 MYO1NFAhdk1? M1iw[lAuPzJiaB?= NVHKcolrcW6mdXPld{BieG:ydH;zbZMhcW5iYTD0bY1mNWSncHXu[IVvfCCvYX7u[ZI> MXiyNVM4OTR2Nh?=
Ramos NX;KZnA{SXCxcITvd4l{KEG|c3H5 MUi1NFAhdk1? NELpfosxNTd{IHi= NWTid5MxcW6mdXPld{BieG:ydH;zbZMhcW5iYTD0bY1mNWSncHXu[IVvfCCvYX7u[ZI> MYKyNVM4OTR2Nh?=
Raji Mm\nRZBweHSxc3nzJGF{e2G7 NFu4VHg2ODBibl2= M3;3blAuPzJiaB?= MoW1bY5lfWOnczDhdI9xfG:|aYOgbY4h[SC2aX3lMYRmeGWwZHXueEBu[W6wZYK= MWGyNVM4OTR2Nh?=
Daudi  M2KybWFxd3C2b4Ppd{BCe3OjeR?= NYTFNlczPTByIH7N Ml20NE04OiCq NUT4epdFcW6mdXPld{BieG:ydH;zbZMhcW5iYTD0bY1mNWSncHXu[IVvfCCvYX7u[ZI> Mnq2NlE{PzF2NE[=
L428 MWLBdI9xfG:|aYOgRZN{[Xl? NVrRc|ZVPTByIH7N Mni5NE04OiCq M4rZUYlv\HWlZYOgZZBweHSxc3nzJIlvKGFidHnt[U1l\XCnbnTlcpQhdWGwbnXy NHrlSmQzOTN5MUS0Oi=>
KM-H2 NYTve5R{SXCxcITvd4l{KEG|c3H5 NUTDNVdbPTByIH7N Ml[1NE04OiCq M1\K[4lv\HWlZYOgZZBweHSxc3nzJIlvKGFidHnt[U1l\XCnbnTlcpQhdWGwbnXy NF7mVWUzOTN5MUS0Oi=>
HDLM-2 M12zWWFxd3C2b4Ppd{BCe3OjeR?= MoTpOVAxKG6P M4nne|AuPzJiaB?= MnvjbY5lfWOnczDhdI9xfG:|aYOgbY4h[SC2aX3lMYRmeGWwZHXueEBu[W6wZYK= M3PnblIyOzdzNES2
L450 M4rNNmFxd3C2b4Ppd{BCe3OjeR?= MmOyOVAxKG6P NXPDdG5kOC15MjDo MVXpcoR2[2W|IHHwc5B1d3OrczDpckBiKHSrbXWt[IVx\W6mZX70JI1idm6nch?= M3rj[lIyOzdzNES2
SW620 NG[yPWtIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1XNcGVEPTB;MUFCtVIvOSCwTR?= M1izN|IyOjR3MEmw
HCT116 NH7IW2tIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mn3JSWM2OD1zMdMxN{4{KG6P NF[xXJAzOTJ2NUC5NC=>
MDA-MB-435 NE\YVoZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGTFZm8xNTFyMECwJI5O MoTlNk02KGR? Mk[zSG1UVw>? M{PE[WlEPTB;MUK1JI5O NX;SVmhNOjBzN{W5NlY>
MDA-MB-468 MUDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MmryNE0yODByMDDuUS=> MXiyMVUh\A>? NGHXSo9FVVOR NWX3blhPUUN3ME2xOEBvVQ>? M4XlSFIxOTd3OUK2
MDA-MB-231 NXnCflNFT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MkXuNE0yODByMDDuUS=> MknINk02KGR? NWiyRlNJTE2VTx?= MVTJR|UxRTFyNTDuUS=> MV:yNFE4PTl{Nh?=
BT474 NHXUPFFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3;VclAuOTByMECgcm0> NXexR2puOi13IHS= NXfZWW9OTE2VTx?= MmDhTWM2OD16IH7N MmXtNlAyPzV7Mk[=
MDA-MB-361 M1\CfWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NIXWNVMxNTFyMECwJI5O MoPPNk02KGR? Ml;lSG1UVw>? MYfJR|UxRTdyIH7N MUmyNFE4PTl{Nh?=
HER18 NX:wNXl{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnzCNE0yODByMDDuUS=> M{f5T|IuPSCm MUnEUXNQ MYnJR|UxRTJyIH7N MX2yNFE4PTl{Nh?=
HER18 MVXBdI9xfG:|aYOgRZN{[Xl? NHPib3QyODBibl2= MX2wM|I1NzR6IHi= NXPMZ4R4TE2VTx?= MUfpcoR2[2W|IHHwc5B1d3OrczDhcoQhemWmdXPld{BkdG:wb3flcolkKHCxdHXueIlidA>? M33DPVIxOTd3OUK2
MDA-MB-231 M4PmR2Fxd3C2b4Ppd{BCe3OjeR?= MofENVA2KG6P NFrJTlQxNzJ2L{S4JIg> NVLH[3lmTE2VTx?= Ml7XbY5lfWOnczDhdI9xfG:|aYOgZY5lKHKnZIXj[ZMh[2yxbn;n[Y5q[yCyb4TlcpRq[Wx? NUHlfXdjOjBzN{W5NlY>
JHH-1 NVrMNYR4T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MX2wMlPjiJNzMECwxsBvVQ>? M4jG[VczKGh? MUDFR|UxRTF5LkVCtVEvOCCwTR?= M3npdFE6QTF|OUO1
JHH-2 NWD2[3BiT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MlXHNE4{6oDVMUCwNOKhdk1? MVm3NkBp MVTFR|UxRTJzOD6wxtEyOC56IH7N NV\yN5IzOTl7MUO5N|U>
JHH-4 Mn6xS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M37BXlAvO+LCk{GwNFDDqG6P NFO5V|Q4OiCq NF3zW4FGSzVyPUG1OU43yrFzNj64JI5O NUPFSJVEOTl7MUO5N|U>
HuH-1 MUfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGTUV4sxNjQkgKOxNFAxyqCwTR?= NG[3cWk4OiCq NH\jZXZGSzVyPUK3MlPDuTVwMDDuUS=> NFnnfnUyQTlzM{mzOS=>
HuH-6 MU\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnTFNE4{6oDVMUCwNOKhdk1? NHvZSXQ4OiCq MYrFR|UxRTNwN9MxNE43KG6P M3n5eFE6QTF|OUO1
HuH-7 M2jMW2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mnv1NE4{6oDVMUCwNOKhdk1? NIfaWIU4OiCq MofTSWM2OD14LklCtVAvOyCwTR?= M4XjV|E6QTF|OUO1
HLE M4q1eGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MkXhNE4{6oDVMUCwNOKhdk1? M2TKc|czKGh? Mon4SWM2OD12NT65xtE3NjRibl2= NGXi[mUyQTlzM{mzOS=>
HLF NV\PNW1lT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NF20UWYxNjQkgKOxNFAxyqCwTR?= M1jBOFczKGh? NFTEVIJGSzVyPUGyOk4yyrFzMj6yJI5O M3rsVVE6QTF|OUO1
PLC/PRF/5 M3r2TWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGnQfG8xNjQkgKOxNFAxyqCwTR?= MlH0O|IhcA>? M2PxRWVEPTB;N{[uPeKyQS57IH7N M4HZ[FE6QTF|OUO1
SK-Hep1 Ml2xS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1jGNFAvO+LCk{GwNFDDqG6P MUm3NkBp MWjFR|UxRTJzLkpCtVEvOiCwTR?= NYri[ZBGOTl7MUO5N|U>
Hep3B NGHNTWVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1rmOVAvO+LCk{GwNFDDqG6P NGi2eXc4OiCq MXXFR|UxRTdwNtMxNU4zKG6P MVOxPVkyOzl|NR?=
HepG2 MmrxS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1SyR|AvO+LCk{GwNFDDqG6P NX[1[m9iPzJiaB?= NIn3OmRGSzVyPUG0MlfDuTFwNzDuUS=> NVTWZVdPOTl7MUO5N|U>
Ramos MlLIRZBweHSxc3nzJGF{e2G7 MlTjNlUwPTBxMUCwJI5O NYLtc3ZCPDhiaB?= Mn71bY5kemWjc3XzJJRp\SCuZY\lcJMhd2ZidHjlJINt\WG4ZXSg[o9zdXNib3[gVGFTWCCjbnSgZ4F{eGG|ZTCz NHPIemkyQTh{M{G2PC=>
Daudi  NXviV4dXSXCxcITvd4l{KEG|c3H5 M1XvRVI2NzVyL{GwNEBvVQ>? MVS0PEBp NUCzSYZvcW6lcnXhd4V{KHSqZTDs[ZZmdHNib3[geIhmKGOuZXH2[YQh\m:{bYOgc4YhWEGUUDDhcoQh[2G|cHHz[UA{ Mn;2NVk5OjNzNki=
BALM-14 M2DOOmFxd3C2b4Ppd{BCe3OjeR?= M1\xR|EzNjVxMkWvOVAhdk1? NUD3Rms2PDhiaB?= MVLpcoNz\WG|ZYOgeIhmKGyndnXsd{Bw\iC2aHWgZ4xm[X[nZDDmc5JueyCxZjDQRXJRKGGwZDDjZZNx[XOnIEO= M1vnR|E6QDJ|MU[4
BALM-27 M3nJeWFxd3C2b4Ppd{BCe3OjeR?= M{exdFEzNjVxMkWvOVAhdk1? Mn3EOFghcA>? NVLTfnBQcW6lcnXhd4V{KHSqZTDs[ZZmdHNib3[geIhmKGOuZXH2[YQh\m:{bYOgc4YhWEGUUDDhcoQh[2G|cHHz[UA{ MUGxPVgzOzF4OB?=
NB4 M3nx[2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MXKwMlAyNzBwMT:xJO69VQ>? M2PEdFQ5KGh? NIrNW4xqdmirYnn0d{Bk\WyuIHfyc5d1cCC|aXfubYZq[2GwdHz5 NFrafpQyQDN4N{S4OC=>

... Click to View More Cell Line Experimental Data

In vivo試験 Administration of AZD1152 (25 mg/kg) alone markedly suppresses the growth of MOLM13 xenografts, confirmed by the observation of necrotic tissue with infiltration of phagocytic cells. [1] In addition, AZD1152 (10-150 mg/kg/day) significantly inhibits the growth of a variety of human solid tumor xenografts, including colon, breast, and lung cancers, in a dose-dependent manner. [2]
臨床試験 A Phase I study to assess the safety and tolerability of AZD1152-HQPA in combination with low dose cytosine arabinoside (LDAC) in patients with acute myeloid leukaemia (AML) has been completed.
特集

プロトコル (参考用のみ)

細胞アッセイ: [1]

細胞株 HL-60, NB4, MOLM13, PALL-2, MV4-11, EOL-1, and K562 cells
濃度 Dissolved in DMSO, final concentrations ~100 nM
反応時間 24 or 48 hours
実験の流れ Cells are exposed to various concentrations of AZD1152 for 24 or 48 hours. Cell proliferation is measured by 3H-thymidine uptake (isotope added 6 hours before harvest), and the concentration that induced 50% growth inhibition (IC50) is calculated from dose-response curves. Cell cycle analysis is performed by flow cytometry. Cell apoptosis is measured by annexin V–FITC apoptosis detection kit.

動物実験: [1]

動物モデル Female immune-deficient BALB/c nude mice subcutaneously injected with MOLM13 cells
製剤 Dissolved in 3M Tris, pH 9.0, at a concentration of 2.5 mg/mL
投薬量 5 or 25 mg/kg
投与方法 Intraperitoneal injection 4 times a week or every another day

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesMouseRatRabbitGuinea pigHamsterDogMonkeyBaboon
Weight (kg)0.020.151.80.40.0810312
Body Surface Area (m2)0.0070.0250.150.050.020.50.240.6
Km factor361285201220
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)
1

参考

化学情報

Download Barasertib (AZD1152-HQPA) SDF
分子量 507.56
化学式

C26H30FN7O3

CAS No. 722544-51-6
保管 3年-20℃
2年-80℃in solvent
別名 INH 34
溶解度 (25°C) * In vitro DMSO 102 mg/mL (200.96 mM)
Ethanol 3 mg/mL (5.91 mM)
Water <1 mg/mL
In vivo 30% PEG 400+0.5% Tween 80+5% Propylene glycol 30mg/mL
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
化学名 2-(5-(7-(3-(ethyl(2-hydroxyethyl)amino)propoxy)quinazolin-4-ylamino)-1H-pyrazol-3-yl)-N-(3-fluorophenyl)acetamide

文献中の引用 (23)

Frequently Asked Questions

  • Question 1
    Can you let me know what solvent I can use for Barasertib, cat # S1147, for in vivo use? (IP injection in mice)

    Answer: S1147 Barasertib (AZD1152-HQPA) can be dissolved in 30% PEG400/0.5% Tween80/5% Propylene glycol at 30mg/ml as a clear solution. Usually, when prepare the solution, we will add organic solvents first, then add Tween 80, then water. But this compound can not dissolve in 30% PEG400/0.5% Tween80/5% Propylene glycol clearly. After water was added, it became a clear solution.

技術サポート&よくある質問(FAQ)

ストックの作り方、阻害剤の保管する方法、細胞実験や動物実験に注意すべきな点を全部含めており、製品を取扱う時よくあった質問に対して取扱説明書でお答えいたします。

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    MLN8054は一種の有効的で、選択性的なオーロラA阻害剤で、Sf9昆虫細胞でIC50値が4 nMです。MLN8054は、オーロラAに作用する選択性はオーロラ Bに作用する選択性より40倍が高くなります。臨床1期。

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
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