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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電話番号: + 81 3-5632-9610mail@cosmobio.co.jp

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 NGewdm1Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlTQNE02ODBibl2= M1TjS|Q5yqCq NILsV2VKSzVyPUK1JI5O Mn[5NlUzPzd4NUm=
LNCaP MVPBdI9xfG:|aYOgRZN{[Xl? MoXtNE02ODBibl2= NHTnZVQ1QMLiaB?= MYjpcoR2[2W|IHHwc5B1d3SrYzDj[YxtKGSnYYToJJRpem:3Z3igZ4F{eGG|ZT2zJJVxemWpdXzheIlwdg>? M2\iZ|I2Ojd5NkW5
LNCaP MnXoSpVv[3Srb36gRZN{[Xl? MV21NEBvVQ>? MlqwOFghcA>? MVjpcoR2[2W|IH3pZ5JwdnWlbHXpJJdqfGhiYX7leYdmdmmlIH3lZ4hidmm|bR?= NYnCZ45HOjV{N{e2OVk>
Ramos NXvrZY5qTnWwY4Tpc44hSXO|YYm= Mn:xOVAxKG6P NF:1VoExNTd{IHi= NVTkWWhVcW6qaXLpeJMhSXW{b4LhJGIhc2mwYYPl NXvOTY03OjF|N{G0OFY>
Daudi  M3PwOWZ2dmO2aX;uJGF{e2G7 NXr3Z5pnPTByIH7N NG\EdGYxNTd{IHi= M{D5[olvcGmkaYTzJGF2em:{YTDCJItqdmG|ZR?= M1HmTVIyOzdzNES2
L540 M4TZZ2Z2dmO2aX;uJGF{e2G7 MmnWOVAxKG6P M{S1T|AuPzJiaB?= MXPpcohq[mm2czDBeZJwemFiQjDrbY5ie2V? M4Hkc|IyOzdzNES2
BJAJ Mn\mS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mlj0OVAxKG6P MUewMVczKGh? MnHEbY5pcWKrdIOgZ4VtdCCpcn;3eIghe2mpbnnmbYNidnSueR?= MUWyNVM4OTR2Nh?=
Ramos NYnXc3BbT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWDZXXR6PTByIH7N M2DvelAuPzJiaB?= MVvpcohq[mm2czDj[YxtKGe{b4f0bEB{cWewaX\pZ4FvfGy7 NInueXgzOTN5MUS0Oi=>
Raji M3jlTGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NID1bII2ODBibl2= MYWwMVczKGh? Mm\QbY5pcWKrdIOgZ4VtdCCpcn;3eIghe2mpbnnmbYNidnSueR?= Ml\CNlE{PzF2NE[=
Daudi  NUTHfm1MT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVy1NFAhdk1? NE\sUWExNTd{IHi= NX;XfpVOcW6qaXLpeJMh[2WubDDndo94fGhic3nncolncWOjboTsfS=> MlLDNlE{PzF2NE[=
L428 NHriUY5Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NUPlXo9GPTByIH7N Mn\JNE04OiCq MlLTbY5pcWKrdIOgZ4VtdCCpcn;3eIg> M4PST|IyOzdzNES2
KM-H2 M3HzcWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MWm1NFAhdk1? M{LTblAuPzJiaB?= Mmi3bY5pcWKrdIOgZ4VtdCCpcn;3eIg> MonSNlE{PzF2NE[=
HDLM-2 NUTiVJVoT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Ml7COVAxKG6P MVKwMVczKGh? NH[3dZBqdmirYnn0d{Bk\WyuIHfyc5d1cA>? M2PKVVIyOzdzNES2
L450 NH:1[ohIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MljJOVAxKG6P MmfWNE04OiCq M2nWeYlvcGmkaYTzJINmdGxiZ4Lve5Rp NYfO[FB6OjF|N{G0OFY>
BJAJ NUnIVFY3SXCxcITvd4l{KEG|c3H5 NG\lNII2ODBibl2= MYWwMVczKGh? M2\DVolv\HWlZYOgZZBweHSxc3nzJIlvKGFidHnt[U1l\XCnbnTlcpQhdWGwbnXy Mn\QNlE{PzF2NE[=
Ramos NE\mfpdCeG:ydH;zbZMhSXO|YYm= NEHNcnY2ODBibl2= M1HaW|AuPzJiaB?= NX:z[WFOcW6mdXPld{BieG:ydH;zbZMhcW5iYTD0bY1mNWSncHXu[IVvfCCvYX7u[ZI> MXGyNVM4OTR2Nh?=
Raji NV70fZNOSXCxcITvd4l{KEG|c3H5 MXO1NFAhdk1? MWKwMVczKGh? MoHlbY5lfWOnczDhdI9xfG:|aYOgbY4h[SC2aX3lMYRmeGWwZHXueEBu[W6wZYK= M1X5RlIyOzdzNES2
Daudi  NV[x[ohJSXCxcITvd4l{KEG|c3H5 M1vjTVUxOCCwTR?= NFTaUmwxNTd{IHi= Ml3vbY5lfWOnczDhdI9xfG:|aYOgbY4h[SC2aX3lMYRmeGWwZHXueEBu[W6wZYK= M3jjZ|IyOzdzNES2
L428 Ml7DRZBweHSxc3nzJGF{e2G7 NWixSGIxPTByIH7N MWiwMVczKGh? MlPGbY5lfWOnczDhdI9xfG:|aYOgbY4h[SC2aX3lMYRmeGWwZHXueEBu[W6wZYK= MXSyNVM4OTR2Nh?=
KM-H2 MVzBdI9xfG:|aYOgRZN{[Xl? MoruOVAxKG6P MljpNE04OiCq NWjHd|FocW6mdXPld{BieG:ydH;zbZMhcW5iYTD0bY1mNWSncHXu[IVvfCCvYX7u[ZI> M{Xs[|IyOzdzNES2
HDLM-2 MXHBdI9xfG:|aYOgRZN{[Xl? NV;GNpBJPTByIH7N MkH4NE04OiCq M{HWbYlv\HWlZYOgZZBweHSxc3nzJIlvKGFidHnt[U1l\XCnbnTlcpQhdWGwbnXy NFm0OXYzOTN5MUS0Oi=>
L450 NWO3do5SSXCxcITvd4l{KEG|c3H5 M2KxW|UxOCCwTR?= NYnxfml5OC15MjDo NGK1d45qdmS3Y3XzJIFxd3C2b4Ppd{BqdiCjIITpcYUu\GWyZX7k[Y51KG2jbn7ldi=> MV:yNVM4OTR2Nh?=
SW620 MmnoS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NIPmbW5GSzVyPUGwxtEzNjFibl2= MnqyNlEzPDVyOUC=
HCT116 NGXkTGdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NEO0UZJGSzVyPUGxxtE{NjNibl2= NX\lZ29TOjF{NEWwPVA>
MDA-MB-435 M3e1U2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MnG3NE0yODByMDDuUS=> MmftNk02KGR? MkXqSG1UVw>? NHvUV5ZKSzVyPUGyOUBvVQ>? NYD5[IJtOjBzN{W5NlY>
MDA-MB-468 NXGyd3NVT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYmwMVExODByIH7N MVWyMVUh\A>? M{\0dGROW09? NHPVfmJKSzVyPUG0JI5O NFLpVIwzODF5NUmyOi=>
MDA-MB-231 MnK4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYSwMVExODByIH7N NF;z[oUzNTViZB?= Mnz4SG1UVw>? NX\YR5NnUUN3ME2xNFUhdk1? NIi1OGszODF5NUmyOi=>
BT474 NGP3W5FIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWXiWG9lOC1zMECwNEBvVQ>? MknSNk02KGR? MkDzSG1UVw>? NFnrPFJKSzVyPUigcm0> M1vzNlIxOTd3OUK2
MDA-MB-361 MnrVS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGTyfHcxNTFyMECwJI5O NIf3b4UzNTViZB?= M2TERWROW09? M1fR[WlEPTB;N{Cgcm0> M{TDSlIxOTd3OUK2
HER18 MVnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MmDkNE0yODByMDDuUS=> NI\pSogzNTViZB?= M4rUdmROW09? MVzJR|UxRTJyIH7N MWmyNFE4PTl{Nh?=
HER18 NHnMOnBCeG:ydH;zbZMhSXO|YYm= NWjoemdROTByIH7N NX;zeVExOC9{ND:0PEBp M{XJO2ROW09? NV2zb21YcW6mdXPld{BieG:ydH;zbZMh[W6mIILl[JVk\XNiY3zvco9o\W6rYzDwc5RmdnSrYXy= MmP1NlAyPzV7Mk[=
MDA-MB-231 Mmn2RZBweHSxc3nzJGF{e2G7 NYXkTWhIOTB3IH7N MXSwM|I1NzR6IHi= NGjnc2RFVVOR NXvzTGVYcW6mdXPld{BieG:ydH;zbZMh[W6mIILl[JVk\XNiY3zvco9o\W6rYzDwc5RmdnSrYXy= NYPXW5lzOjBzN{W5NlY>
JHH-1 NGm3Z2tIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MXmwMlPjiJNzMECwxsBvVQ>? NYG2e|lHPzJiaB?= M371WmVEPTB;MUeuOOKyOS5yIH7N M3\yXlE6QTF|OUO1
JHH-2 M{Lsd2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVewMlPjiJNzMECwxsBvVQ>? MUG3NkBp NFrMZodGSzVyPUKxPE4xyrFzMD64JI5O NFjYOHYyQTlzM{mzOS=>
JHH-4 MmLFS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWri[Yt4OC5|4pETNVAxOMLibl2= MX23NkBp MlvRSWM2OD1zNUWuOuKyOTZwODDuUS=> NGfmdpEyQTlzM{mzOS=>
HuH-1 NFfqT|NIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVjaW29{OC5|4pETNVAxOMLibl2= NHjvWFQ4OiCq NWOxemllTUN3ME2yO{4{yrF3LkCgcm0> MnjQNVk6OTN7M{W=
HuH-6 NFzBcFZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYewMlPjiJNzMECwxsBvVQ>? M2nidFczKGh? NITvWGJGSzVyPUOuO:KyOC54IH7N NW[xUW5HOTl7MUO5N|U>
HuH-7 MX3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M4\TRVAvO+LCk{GwNFDDqG6P MnSwO|IhcA>? MkPJSWM2OD14LklCtVAvOyCwTR?= MkS2NVk6OTN7M{W=
HLE MYTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFjJeXkxNjQkgKOxNFAxyqCwTR?= NE\hXGE4OiCq Moi3SWM2OD12NT65xtE3NjRibl2= M2TiTVE6QTF|OUO1
HLF NGeyfnJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmiwNE4{6oDVMUCwNOKhdk1? NWPUUpJ2PzJiaB?= NHjZbnZGSzVyPUGyOk4yyrFzMj6yJI5O NWHISHkzOTl7MUO5N|U>
PLC/PRF/5 MmDoS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{PzelAvO+LCk{GwNFDDqG6P NF;JToQ4OiCq MnXkSWM2OD15Nj65xtE6Njlibl2= MYexPVkyOzl|NR?=
SK-Hep1 MUTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NWL6TXJyOC5|4pETNVAxOMLibl2= M4\R[FczKGh? NIWxVYpGSzVyPUKxMlnDuTFwMjDuUS=> MX6xPVkyOzl|NR?=
Hep3B NIXGOYhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MXGwMlPjiJNzMECwxsBvVQ>? M{DMO|czKGh? Mn7SSWM2OD15LkdCtVEvOiCwTR?= M1vKZ|E6QTF|OUO1
HepG2 NEXmcpNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFW5fJQxNjQkgKOxNFAxyqCwTR?= NHT4d|g4OiCq MkK5SWM2OD1zND63xtEyNjdibl2= NUHUPXVwOTl7MUO5N|U>
Ramos NUPveIR2SXCxcITvd4l{KEG|c3H5 NUnSc25WOjVxNUCvNVAxKG6P MWm0PEBp MY\pcoNz\WG|ZYOgeIhmKGyndnXsd{Bw\iC2aHWgZ4xm[X[nZDDmc5JueyCxZjDQRXJRKGGwZDDjZZNx[XOnIEO= NHPPNG0yQTh{M{G2PC=>
Daudi  M1nVfWFxd3C2b4Ppd{BCe3OjeR?= MnzhNlUwPTBxMUCwJI5O M{njflQ5KGh? MYPpcoNz\WG|ZYOgeIhmKGyndnXsd{Bw\iC2aHWgZ4xm[X[nZDDmc5JueyCxZjDQRXJRKGGwZDDjZZNx[XOnIEO= M2j6N|E6QDJ|MU[4
BALM-14 NUfNdpdYSXCxcITvd4l{KEG|c3H5 MnjYNVIvPS9{NT:1NEBvVQ>? MWS0PEBp NUXzXpI3cW6lcnXhd4V{KHSqZTDs[ZZmdHNib3[geIhmKGOuZXH2[YQh\m:{bYOgc4YhWEGUUDDhcoQh[2G|cHHz[UA{ MY[xPVgzOzF4OB?=
BALM-27 Mn7JRZBweHSxc3nzJGF{e2G7 NVrSe5JFOTJwNT:yOU82OCCwTR?= NHfyU5o1QCCq M3iyXolv[3KnYYPld{B1cGVibHX2[Yx{KG:oIITo[UBkdGWjdnXkJIZwem2|IH;mJHBCWlBiYX7kJINie3Cjc3WgNy=> NXfvVnRROTl6MkOxOlg>
NB4 M2jwVGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1\rcVAvODFxMD6xM|Eh|ryP MkPhOFghcA>? MofvbY5pcWKrdIOgZ4VtdCCpcn;3eIghe2mpbnnmbYNidnSueR?= NEPFZ2syQDN4N{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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