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 NILx[ZVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2[3[FAuPTByIH7N M3HmPFQ5yqCq NEPvUI5KSzVyPUK1JI5O MlrjNlUzPzd4NUm=
LNCaP MnnwRZBweHSxc3nzJGF{e2G7 Mom4NE02ODBibl2= NGG3WWU1QMLiaB?= NVj1XVAxcW6mdXPld{BieG:ydH;0bYMh[2WubDDk[YF1cCC2aILveYdpKGOjc4Dhd4UuOyC3cILl[5Vt[XSrb36= NY\F[G1yOjV{N{e2OVk>
LNCaP MknxSpVv[3Srb36gRZN{[Xl? NHXCN3U2OCCwTR?= MkK4OFghcA>? MkTWbY5lfWOnczDtbYNzd263Y3zlbUB4cXSqIHHu[ZVo\W6rYzDt[YNp[W6rc32= NWPpZnROOjV{N{e2OVk>
Ramos NGPBWXRHfW6ldHnvckBCe3OjeR?= MXy1NFAhdk1? MXWwMVczKGh? M3njWolvcGmkaYTzJGF2em:{YTDCJItqdmG|ZR?= MljBNlE{PzF2NE[=
Daudi  Mo[4SpVv[3Srb36gRZN{[Xl? NFz0R|Q2ODBibl2= M{\rXVAuPzJiaB?= MX;pcohq[mm2czDBeZJwemFiQjDrbY5ie2V? NFXoPWgzOTN5MUS0Oi=>
L540 NFz0RYJHfW6ldHnvckBCe3OjeR?= NFG5R3M2ODBibl2= NYPnZohFOC15MjDo NFXZNlZqdmirYnn0d{BCfXKxcnGgRkBscW6jc3W= NYD0cJB5OjF|N{G0OFY>
BJAJ NYTUUGtvT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NEHrbJc2ODBibl2= M4PwXlAuPzJiaB?= MmrLbY5pcWKrdIOgZ4VtdCCpcn;3eIghe2mpbnnmbYNidnSueR?= M3THcFIyOzdzNES2
Ramos MUnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NWXXTmJPPTByIH7N MXKwMVczKGh? NXLqRpNncW6qaXLpeJMh[2WubDDndo94fGhic3nncolncWOjboTsfS=> MnK5NlE{PzF2NE[=
Raji NXntXpVQT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NW\6Wms6PTByIH7N NUfUPVZvOC15MjDo MYLpcohq[mm2czDj[YxtKGe{b4f0bEB{cWewaX\pZ4FvfGy7 NVnyT3ZoOjF|N{G0OFY>
Daudi  NF7jNYFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M{Wz[FUxOCCwTR?= M{\kVVAuPzJiaB?= NW[5SXNEcW6qaXLpeJMh[2WubDDndo94fGhic3nncolncWOjboTsfS=> M1PIW|IyOzdzNES2
L428 MkfFS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1LpeFUxOCCwTR?= M2XDdVAuPzJiaB?= NIe0V4dqdmirYnn0d{Bk\WyuIHfyc5d1cA>? M1vNSVIyOzdzNES2
KM-H2 NFj2dm5Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmPJOVAxKG6P NUfobmo5OC15MjDo M{D2[YlvcGmkaYTzJINmdGxiZ4Lve5Rp NWXTTGNzOjF|N{G0OFY>
HDLM-2 MluyS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYjwXnV1PTByIH7N NILJ[3cxNTd{IHi= MVzpcohq[mm2czDj[YxtKGe{b4f0bC=> MWCyNVM4OTR2Nh?=
L450 MoPuS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYq1NFAhdk1? MoXINE04OiCq NVW3dmpUcW6qaXLpeJMh[2WubDDndo94fGh? MYOyNVM4OTR2Nh?=
BJAJ M2SyPGFxd3C2b4Ppd{BCe3OjeR?= NGT0SW42ODBibl2= NXz6eWJqOC15MjDo MVLpcoR2[2W|IHHwc5B1d3OrczDpckBiKHSrbXWt[IVx\W6mZX70JI1idm6nch?= M4[3TVIyOzdzNES2
Ramos M2rpdWFxd3C2b4Ppd{BCe3OjeR?= MXe1NFAhdk1? M{LS[lAuPzJiaB?= NIHIfIFqdmS3Y3XzJIFxd3C2b4Ppd{BqdiCjIITpcYUu\GWyZX7k[Y51KG2jbn7ldi=> MmGxNlE{PzF2NE[=
Raji M4nYNGFxd3C2b4Ppd{BCe3OjeR?= MXG1NFAhdk1? M1\ET|AuPzJiaB?= NH3ZfmpqdmS3Y3XzJIFxd3C2b4Ppd{BqdiCjIITpcYUu\GWyZX7k[Y51KG2jbn7ldi=> NUjDfpdqOjF|N{G0OFY>
Daudi  NY\WXFVqSXCxcITvd4l{KEG|c3H5 M3raNVUxOCCwTR?= Mm\vNE04OiCq MmTmbY5lfWOnczDhdI9xfG:|aYOgbY4h[SC2aX3lMYRmeGWwZHXueEBu[W6wZYK= MVKyNVM4OTR2Nh?=
L428 MnLmRZBweHSxc3nzJGF{e2G7 MUW1NFAhdk1? M{[xd|AuPzJiaB?= NH\N[JhqdmS3Y3XzJIFxd3C2b4Ppd{BqdiCjIITpcYUu\GWyZX7k[Y51KG2jbn7ldi=> NIi1b|AzOTN5MUS0Oi=>
KM-H2 NF3neXhCeG:ydH;zbZMhSXO|YYm= MX21NFAhdk1? NIrtZYwxNTd{IHi= MWDpcoR2[2W|IHHwc5B1d3OrczDpckBiKHSrbXWt[IVx\W6mZX70JI1idm6nch?= NV76d3JbOjF|N{G0OFY>
HDLM-2 MXTBdI9xfG:|aYOgRZN{[Xl? MUO1NFAhdk1? MnXLNE04OiCq NUjvblkzcW6mdXPld{BieG:ydH;zbZMhcW5iYTD0bY1mNWSncHXu[IVvfCCvYX7u[ZI> NUfqTpVSOjF|N{G0OFY>
L450 MVTBdI9xfG:|aYOgRZN{[Xl? NGPRVZA2ODBibl2= NUnpTW1COC15MjDo NFHLZY5qdmS3Y3XzJIFxd3C2b4Ppd{BqdiCjIITpcYUu\GWyZX7k[Y51KG2jbn7ldi=> NIrUXWozOTN5MUS0Oi=>
SW620 MWjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXzFR|UxRTFywsGyMlEhdk1? MVuyNVI1PTB7MB?=
HCT116 NED4eIRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MkCxSWM2OD1zMdMxN{4{KG6P MYmyNVI1PTB7MB?=
MDA-MB-435 M2rZO2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWTmdFRPOC1zMECwNEBvVQ>? NUDTOmIzOi13IHS= Mlz4SG1UVw>? NVPIOJZvUUN3ME2xNlUhdk1? NU\0V3BwOjBzN{W5NlY>
MDA-MB-468 NYf0UGNNT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYf2XnM6OC1zMECwNEBvVQ>? NEPuU3czNTViZB?= M2XDcGROW09? NFzwWotKSzVyPUG0JI5O MUOyNFE4PTl{Nh?=
MDA-MB-231 MV3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MkjkNE0yODByMDDuUS=> NYPWeVBLOi13IHS= Mn7uSG1UVw>? Ml36TWM2OD1zMEWgcm0> MUGyNFE4PTl{Nh?=
BT474 M{XPVWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHPEZWwxNTFyMECwJI5O NGHieIYzNTViZB?= NVzwT2FYTE2VTx?= MXTJR|UxRThibl2= MX2yNFE4PTl{Nh?=
MDA-MB-361 M2ftPWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFi3W5oxNTFyMECwJI5O NIHJcW0zNTViZB?= M{TGd2ROW09? MlHRTWM2OD15MDDuUS=> NFPtdHQzODF5NUmyOi=>
HER18 NWPjSpY3T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NITrU4YxNTFyMECwJI5O MXyyMVUh\A>? NEXIOoxFVVOR MnHBTWM2OD1{MDDuUS=> NHrTToozODF5NUmyOi=>
HER18 NY\6e5FxSXCxcITvd4l{KEG|c3H5 MXyxNFAhdk1? M37JfFAwOjRxNEigbC=> MWfEUXNQ M4T0PYlv\HWlZYOgZZBweHSxc3nzJIFv\CC{ZXT1Z4V{KGOub37v[4VvcWNicH;0[Y51cWGu MWKyNFE4PTl{Nh?=
MDA-MB-231 NIDnRWNCeG:ydH;zbZMhSXO|YYm= MmL3NVA2KG6P MlLSNE8zPC92ODDo NXjkVldITE2VTx?= M3zEfolv\HWlZYOgZZBweHSxc3nzJIFv\CC{ZXT1Z4V{KGOub37v[4VvcWNicH;0[Y51cWGu NXGxbXZsOjBzN{W5NlY>
JHH-1 NWrXZmx5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MkPkNE4{6oDVMUCwNOKhdk1? NGmwXI44OiCq NIC0XFdGSzVyPUG3MlTDuTFwMDDuUS=> MYexPVkyOzl|NR?=
JHH-2 M1\SdWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MX:wMlPjiJNzMECwxsBvVQ>? M33hN|czKGh? NXr6RWt4TUN3ME2yNVgvOMLzMUCuPEBvVQ>? MYmxPVkyOzl|NR?=
JHH-4 NHPLZYZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXfWbGpTOC5|4pETNVAxOMLibl2= MkHjO|IhcA>? M1npTGVEPTB;MUW1MlbDuTF4Lkigcm0> NWOzO4xPOTl7MUO5N|U>
HuH-1 MVXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NWTWRYM{OC5|4pETNVAxOMLibl2= NFL5d5Q4OiCq NUXIUIxWTUN3ME2yO{4{yrF3LkCgcm0> Mo\aNVk6OTN7M{W=
HuH-6 M2[1dGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NI\qSFIxNjQkgKOxNFAxyqCwTR?= M33aOVczKGh? MWPFR|UxRTNwN9MxNE43KG6P NHHReWYyQTlzM{mzOS=>
HuH-7 M1LXSWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NUjkWoJ3OC5|4pETNVAxOMLibl2= Mk[3O|IhcA>? MnjrSWM2OD14LklCtVAvOyCwTR?= Mnm3NVk6OTN7M{W=
HLE MUDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NWi2e3RnOC5|4pETNVAxOMLibl2= M2rqb|czKGh? NV3ITm1LTUN3ME20OU46yrF4LkSgcm0> MYWxPVkyOzl|NR?=
HLF NUPlNVRXT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MkmxNE4{6oDVMUCwNOKhdk1? NGLLZW44OiCq Ml7mSWM2OD1zMk[uNeKyOTJwMjDuUS=> M1\4SVE6QTF|OUO1
PLC/PRF/5 NGrhd5NIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NYP1coduOC5|4pETNVAxOMLibl2= NVO0VJJ3PzJiaB?= NI\KPHdGSzVyPUe2MlnDuTlwOTDuUS=> MlrLNVk6OTN7M{W=
SK-Hep1 NXfrflJ3T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4\ONFAvO+LCk{GwNFDDqG6P MUS3NkBp M4DFV2VEPTB;MkGuPeKyOS5{IH7N NVnaZ3FPOTl7MUO5N|U>
Hep3B M1vmS2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mn;PNE4{6oDVMUCwNOKhdk1? Mo\rO|IhcA>? MVfFR|UxRTdwNtMxNU4zKG6P NIDmO2gyQTlzM{mzOS=>
HepG2 MoTaS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVv4Omd4OC5|4pETNVAxOMLibl2= MmCzO|IhcA>? NHu3T2dGSzVyPUG0MlfDuTFwNzDuUS=> MoPkNVk6OTN7M{W=
Ramos NVLRfGI1SXCxcITvd4l{KEG|c3H5 M130[|I2NzVyL{GwNEBvVQ>? MUm0PEBp NUHZSWhYcW6lcnXhd4V{KHSqZTDs[ZZmdHNib3[geIhmKGOuZXH2[YQh\m:{bYOgc4YhWEGUUDDhcoQh[2G|cHHz[UA{ NX2wfHBYOTl6MkOxOlg>
Daudi  NUjwN2ZJSXCxcITvd4l{KEG|c3H5 NGe1NHIzPS93MD:xNFAhdk1? NXHKb5VFPDhiaB?= MmTUbY5kemWjc3XzJJRp\SCuZY\lcJMhd2ZidHjlJINt\WG4ZXSg[o9zdXNib3[gVGFTWCCjbnSgZ4F{eGG|ZTCz MUCxPVgzOzF4OB?=
BALM-14 MlLvRZBweHSxc3nzJGF{e2G7 NWe4bodQOTJwNT:yOU82OCCwTR?= NFnRfJA1QCCq MknXbY5kemWjc3XzJJRp\SCuZY\lcJMhd2ZidHjlJINt\WG4ZXSg[o9zdXNib3[gVGFTWCCjbnSgZ4F{eGG|ZTCz M{\Ob|E6QDJ|MU[4
BALM-27 MV3BdI9xfG:|aYOgRZN{[Xl? NH\IXo8yOi53L{K1M|UxKG6P MXq0PEBp M1zpU4lv[3KnYYPld{B1cGVibHX2[Yx{KG:oIITo[UBkdGWjdnXkJIZwem2|IH;mJHBCWlBiYX7kJINie3Cjc3WgNy=> NITyR2UyQTh{M{G2PC=>
NB4 M2TWPWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NF3xXmIxNjBzL{CuNU8yKM7:TR?= NEDtdo81QCCq MUnpcohq[mm2czDj[YxtKGe{b4f0bEB{cWewaX\pZ4FvfGy7 MVWxPFM3PzR6NB?=

... 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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