Barasertib (AZD1152-HQPA|AZD2811)

Catalog No.S1147 Synonyms: INH 34

Barasertib (AZD1152-HQPA|AZD2811) Chemical Structure

Molecular Weight(MW): 507.56

Barasertib (AZD1152-HQPA) is a highly selective Aurora B inhibitor with IC50 of 0.37 nM in a cell-free assay, ~3700 fold more selective for Aurora B over Aurora A. Phase 1.

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Cited by 29 Publications

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Biological Activity

Description Barasertib (AZD1152-HQPA) is a highly selective Aurora B inhibitor with IC50 of 0.37 nM in a cell-free assay, ~3700 fold more selective for Aurora B over Aurora A. Phase 1.
Targets
Aurora B [1]
(Cell-free assay)
0.37 nM
In vitro

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 Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
LNCaP M{nnUmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2ftNVAuPTByIH7N NVO0SGh1PDkEoHi= M3vBVWlEPTB;MkWgcm0> NIHWblIzPTJ5N{[1PS=>
LNCaP MVXBdI9xfG:|aYOgRZN{[Xl? MWCwMVUxOCCwTR?= MnzFOFjDqGh? Ml74bY5lfWOnczDhdI9xfG:2aXOgZ4VtdCCmZXH0bEB1cHKxdXfoJINie3Cjc3WtN{B2eHKnZ4XsZZRqd25? NUW1bVV[OjV{N{e2OVk>
LNCaP MoHDSpVv[3Srb36gRZN{[Xl? NI\QOWk2OCCwTR?= MYm0PEBp M13Ge4lv\HWlZYOgcYlkem:wdXPs[Ykhf2m2aDDhcoV2\2WwaXOgcYVkcGGwaYPt NHPnR2IzPTJ5N{[1PS=>
Ramos MV\GeY5kfGmxbjDBd5NigQ>? MnLiOVAxKG6P MYGwMVczKGh? NXHRe2pZcW6qaXLpeJMhSXW{b4LhJGIhc2mwYYPl MoTQNlE{PzF2NE[=
Daudi  MYHGeY5kfGmxbjDBd5NigQ>? NF\YeIw2ODBibl2= M2TY[|AuPzJiaB?= MkCwbY5pcWKrdIOgRZVzd3KjIFKgb4lv[XOn MXqyNVM4OTR2Nh?=
L540 M2XCcmZ2dmO2aX;uJGF{e2G7 MV61NFAhdk1? MnS2NE04OiCq M3r5colvcGmkaYTzJGF2em:{YTDCJItqdmG|ZR?= NITFZpMzOTN5MUS0Oi=>
BJAJ M{CwbGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mn7DOVAxKG6P NUn5e5NVOC15MjDo MWrpcohq[mm2czDj[YxtKGe{b4f0bEB{cWewaX\pZ4FvfGy7 M2Xxe|IyOzdzNES2
Ramos NGfjWHJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NV[3dWtvPTByIH7N NEf2SnoxNTd{IHi= NIPaTY5qdmirYnn0d{Bk\WyuIHfyc5d1cCC|aXfubYZq[2GwdHz5 MnzJNlE{PzF2NE[=
Raji M3fQfWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXm2eI9DPTByIH7N M2DEfVAuPzJiaB?= MWPpcohq[mm2czDj[YxtKGe{b4f0bEB{cWewaX\pZ4FvfGy7 NV3TeGtsOjF|N{G0OFY>
Daudi  NH3OblZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NYL3dod{PTByIH7N MorONE04OiCq NGnQcG5qdmirYnn0d{Bk\WyuIHfyc5d1cCC|aXfubYZq[2GwdHz5 NGjwWZEzOTN5MUS0Oi=>
L428 NYfMNJp5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NV;NVZk3PTByIH7N MYOwMVczKGh? MUDpcohq[mm2czDj[YxtKGe{b4f0bC=> MVyyNVM4OTR2Nh?=
KM-H2 NXvCSFFuT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NY\abIh3PTByIH7N NV[0cGZOOC15MjDo MlTnbY5pcWKrdIOgZ4VtdCCpcn;3eIg> NFzrTmEzOTN5MUS0Oi=>
HDLM-2 MWfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M4D5[VUxOCCwTR?= NIPGbGIxNTd{IHi= NG\z[JJqdmirYnn0d{Bk\WyuIHfyc5d1cA>? MWGyNVM4OTR2Nh?=
L450 NW\ZfIdyT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NH7Beok2ODBibl2= MYGwMVczKGh? NYW1SYVOcW6qaXLpeJMh[2WubDDndo94fGh? NH3xZVkzOTN5MUS0Oi=>
BJAJ NYTTWmtFSXCxcITvd4l{KEG|c3H5 MWC1NFAhdk1? MlHVNE04OiCq NFn1fHNqdmS3Y3XzJIFxd3C2b4Ppd{BqdiCjIITpcYUu\GWyZX7k[Y51KG2jbn7ldi=> MnnwNlE{PzF2NE[=
Ramos MnHPRZBweHSxc3nzJGF{e2G7 MojDOVAxKG6P NVnmPW5sOC15MjDo NGO5PY9qdmS3Y3XzJIFxd3C2b4Ppd{BqdiCjIITpcYUu\GWyZX7k[Y51KG2jbn7ldi=> M2mw[|IyOzdzNES2
Raji MlrTRZBweHSxc3nzJGF{e2G7 NEf2S282ODBibl2= M2X0VVAuPzJiaB?= MYTpcoR2[2W|IHHwc5B1d3OrczDpckBiKHSrbXWt[IVx\W6mZX70JI1idm6nch?= MnfQNlE{PzF2NE[=
Daudi  MkfLRZBweHSxc3nzJGF{e2G7 NHTUXoo2ODBibl2= M3;VW|AuPzJiaB?= M2LwSYlv\HWlZYOgZZBweHSxc3nzJIlvKGFidHnt[U1l\XCnbnTlcpQhdWGwbnXy NGK1RYEzOTN5MUS0Oi=>
L428 Mm\lRZBweHSxc3nzJGF{e2G7 NInncIg2ODBibl2= NFvk[oIxNTd{IHi= NV3uTnNJcW6mdXPld{BieG:ydH;zbZMhcW5iYTD0bY1mNWSncHXu[IVvfCCvYX7u[ZI> NIHXRm4zOTN5MUS0Oi=>
KM-H2 MUjBdI9xfG:|aYOgRZN{[Xl? MXO1NFAhdk1? NYXYTVExOC15MjDo M3rwOIlv\HWlZYOgZZBweHSxc3nzJIlvKGFidHnt[U1l\XCnbnTlcpQhdWGwbnXy NUTQSmR6OjF|N{G0OFY>
HDLM-2 MVLBdI9xfG:|aYOgRZN{[Xl? NUfycGxRPTByIH7N NHzQOIcxNTd{IHi= M4nIc4lv\HWlZYOgZZBweHSxc3nzJIlvKGFidHnt[U1l\XCnbnTlcpQhdWGwbnXy MUKyNVM4OTR2Nh?=
L450 MkDmRZBweHSxc3nzJGF{e2G7 M3PWRlUxOCCwTR?= NWO3eHhSOC15MjDo M37FZolv\HWlZYOgZZBweHSxc3nzJIlvKGFidHnt[U1l\XCnbnTlcpQhdWGwbnXy NFfL[|kzOTN5MUS0Oi=>
SW620 M1zSNmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVPFR|UxRTFywsGyMlEhdk1? MXKyNVI1PTB7MB?=
HCT116 NX2wN3lWT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYjFR|UxRTFzwsGzMlMhdk1? MYOyNVI1PTB7MB?=
MDA-MB-435 MWHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXzrNWR{OC1zMECwNEBvVQ>? MXWyMVUh\A>? MXvEUXNQ M3fhOGlEPTB;MUK1JI5O NHjhOnEzODF5NUmyOi=>
MDA-MB-468 NVnRe5JvT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVmwMVExODByIH7N NVXqe3ZrOi13IHS= MkjaSG1UVw>? M1zyNmlEPTB;MUSgcm0> NYOyT5NmOjBzN{W5NlY>
MDA-MB-231 MUDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1m3U|AuOTByMECgcm0> NYDZNlB[Oi13IHS= MUPEUXNQ MlvHTWM2OD1zMEWgcm0> NHPWOZgzODF5NUmyOi=>
BT474 NYPGeoZrT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MUiwMVExODByIH7N NF:xSJgzNTViZB?= M3zlT2ROW09? NG\hXHJKSzVyPUigcm0> Mn;KNlAyPzV7Mk[=
MDA-MB-361 NV\Zcpg1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MkPkNE0yODByMDDuUS=> NHXpXZEzNTViZB?= MmT5SG1UVw>? M1nwbmlEPTB;N{Cgcm0> M4PLeFIxOTd3OUK2
HER18 NFLuNYxIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MkLjNE0yODByMDDuUS=> M3zHTFIuPSCm MYPEUXNQ NX;ze3E{UUN3ME2yNEBvVQ>? NHT1[HIzODF5NUmyOi=>
HER18 Mn\kRZBweHSxc3nzJGF{e2G7 MoP5NVAxKG6P NUjXdWR{OC9{ND:0PEBp M3fBSGROW09? MU\pcoR2[2W|IHHwc5B1d3OrczDhcoQhemWmdXPld{BkdG:wb3flcolkKHCxdHXueIlidA>? NIXFWGEzODF5NUmyOi=>
MDA-MB-231 NH7XNpNCeG:ydH;zbZMhSXO|YYm= NGHOcnkyODVibl2= M3vk[lAwOjRxNEigbC=> M2qzeWROW09? M1i1fIlv\HWlZYOgZZBweHSxc3nzJIFv\CC{ZXT1Z4V{KGOub37v[4VvcWNicH;0[Y51cWGu M122RlIxOTd3OUK2
JHH-1 MWrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGnSfY0xNjQkgKOxNFAxyqCwTR?= MkH0O|IhcA>? MmLTSWM2OD1zNz60xtEyNjBibl2= M2\3NlE6QTF|OUO1
JHH-2 M1;RcWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NYnDdlhUOC5|4pETNVAxOMLibl2= M1:xVFczKGh? M{S1OWVEPTB;MkG4MlDDuTFyLkigcm0> MknFNVk6OTN7M{W=
JHH-4 MXLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2G2bFAvO+LCk{GwNFDDqG6P NFTiW|c4OiCq NG\DflJGSzVyPUG1OU43yrFzNj64JI5O NInFWnIyQTlzM{mzOS=>
HuH-1 MlzMS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHrNb2YxNjQkgKOxNFAxyqCwTR?= MX63NkBp NXH6fpd1TUN3ME2yO{4{yrF3LkCgcm0> M{[4N|E6QTF|OUO1
HuH-6 MlP1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{TST|AvO+LCk{GwNFDDqG6P M3XKS|czKGh? NXHBN4h4TUN3ME2zMlfDuTBwNjDuUS=> M131TVE6QTF|OUO1
HuH-7 NIrwdY5Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MUiwMlPjiJNzMECwxsBvVQ>? NHHkSZE4OiCq Mm\lSWM2OD14LklCtVAvOyCwTR?= NXi0[nlZOTl7MUO5N|U>
HLE MUHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M4DReFAvO+LCk{GwNFDDqG6P NWq5bI94PzJiaB?= MYrFR|UxRTR3LkpCtVYvPCCwTR?= M2LJSVE6QTF|OUO1
HLF NX\GOIMxT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MoH4NE4{6oDVMUCwNOKhdk1? M3S0[|czKGh? MYfFR|UxRTF{Nj6xxtEyOi5{IH7N NH7yNWEyQTlzM{mzOS=>
PLC/PRF/5 MY\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlXYNE4{6oDVMUCwNOKhdk1? MluyO|IhcA>? NEizUW1GSzVyPUe2MlnDuTlwOTDuUS=> MnHMNVk6OTN7M{W=
SK-Hep1 MY\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NVfrbmg3OC5|4pETNVAxOMLibl2= MYO3NkBp MlzBSWM2OD1{MT65xtEyNjJibl2= M{j6b|E6QTF|OUO1
Hep3B NH7Db5JIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGK4bIYxNjQkgKOxNFAxyqCwTR?= M1rJT|czKGh? NFXmdGxGSzVyPUeuOuKyOS5{IH7N MUCxPVkyOzl|NR?=
HepG2 MULHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3niR|AvO+LCk{GwNFDDqG6P MVe3NkBp NVHVT4x5TUN3ME2xOE44yrFzLkegcm0> NH7WWZkyQTlzM{mzOS=>
Ramos MWnBdI9xfG:|aYOgRZN{[Xl? NVj4[5dXOjVxNUCvNVAxKG6P Mo\MOFghcA>? M3uybYlv[3KnYYPld{B1cGVibHX2[Yx{KG:oIITo[UBkdGWjdnXkJIZwem2|IH;mJHBCWlBiYX7kJINie3Cjc3WgNy=> MWqxPVgzOzF4OB?=
Daudi  M{\2[mFxd3C2b4Ppd{BCe3OjeR?= NVHHZpNsOjVxNUCvNVAxKG6P MoTCOFghcA>? MlzqbY5kemWjc3XzJJRp\SCuZY\lcJMhd2ZidHjlJINt\WG4ZXSg[o9zdXNib3[gVGFTWCCjbnSgZ4F{eGG|ZTCz MUWxPVgzOzF4OB?=
BALM-14 NWXpNphTSXCxcITvd4l{KEG|c3H5 NYjtNVhoOTJwNT:yOU82OCCwTR?= MnS4OFghcA>? NFjrfpNqdmO{ZXHz[ZMhfGinIHzleoVteyCxZjD0bIUh[2ynYY\l[EBnd3KvczDv[kBRSVKSIHHu[EBk[XOyYYPlJFM> MWSxPVgzOzF4OB?=
BALM-27 NYX1cYN4SXCxcITvd4l{KEG|c3H5 NX[yU5hmOTJwNT:yOU82OCCwTR?= NIm3[Yg1QCCq NWPDW2tFcW6lcnXhd4V{KHSqZTDs[ZZmdHNib3[geIhmKGOuZXH2[YQh\m:{bYOgc4YhWEGUUDDhcoQh[2G|cHHz[UA{ NES1dJYyQTh{M{G2PC=>
NB4 M3Pp[Gdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MYKwMlAyNzBwMT:xJO69VQ>? MkGxOFghcA>? M2fTN4lvcGmkaYTzJINmdGxiZ4Lve5RpKHOrZ37p[olk[W62bIm= MVyxPFM3PzR6NB?=

... Click to View More Cell Line Experimental Data

Assay
Methods Test Index PMID
Western blot
AURKB / pSer10 Histone H3 / TP53 / CDKN1A / MYCN; 

PubMed: 26497213     


Downstream effects of barasertib-induced AURKB inhibition on histone H3 phosphorylation and TP53 protein levels in IMR5 and SK-N-BE (2c) as indicated after 24h (left) and 48h (right). TP53 and its downstream effector CDKN1A were up-regulated by barasertib䲧疝Ỵ疞㧀疜膉痘 瘿⟸෕ᾰƌ෕Ð 㺣痖帉痖Ѐ瑖堘𢡄빢᎒

p53 / p21 / p-p38 / p38 ; 

PubMed: 24782314     


U2OS cells were treated with 50 nm or 100 nm AZD1152 for 24 h. p21, p38, p-p38, and p53 levels were determined by immunoblotting β-actin served as a loading control.

26497213 24782314
Immunofluorescence
p21 ; 

PubMed: 24782314     


U2OS cells were treated as in H. Levels of p21 were analyzed by immunostaining. DNA was counterstained with Hoechst 33258.

24782314
Growth inhibition assay
Cell viability ; 

PubMed: 26497213     


Dose response curves to barasertib at 72h of incubation normalized to the DMSO control sample (mean ± SD, n = 5). The inset depicts the normalized AUCs of each response curve. 

26497213
In vivo 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]

Protocol

Cell Research:[1]
+ Expand
  • Cell lines: HL-60, NB4, MOLM13, PALL-2, MV4-11, EOL-1, and K562 cells
  • Concentrations: Dissolved in DMSO, final concentrations ~100 nM
  • Incubation Time: 24 or 48 hours
  • Method: 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.
    (Only for Reference)
Animal Research:[1]
+ Expand
  • Animal Models: Female immune-deficient BALB/c nude mice subcutaneously injected with MOLM13 cells
  • Formulation: Dissolved in 3M Tris, pH 9.0, at a concentration of 2.5 mg/mL
  • Dosages: 5 or 25 mg/kg
  • Administration: Intraperitoneal injection 4 times a week or every another day
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 102 mg/mL (200.96 mM)
Ethanol 3 mg/mL (5.91 mM)
Water Insoluble
In vivo Add solvents to the product individually and in order(Data is from Selleck tests instead of citations):
2% DMSO+40% PEG 300+2% Tween 80+ddH2O
For best results, use promptly after mixing.
7mg/mL

* 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.

Chemical Information

Molecular Weight 507.56
Formula

C26H30FN7O3

CAS No. 722544-51-6
Storage powder
in solvent
Synonyms INH 34

Bio Calculators

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Clinical Trial Information

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT03366675 Terminated Small Cell Lung Cancer Samsung Medical Center|AstraZeneca December 1 2017 Phase 2
NCT03366675 Terminated Small Cell Lung Cancer Samsung Medical Center|AstraZeneca December 1 2017 Phase 2
NCT03217838 Recruiting Acute Myeloid Leukaemia AstraZeneca July 31 2017 Phase 1|Phase 2
NCT03217838 Recruiting Acute Myeloid Leukaemia AstraZeneca July 31 2017 Phase 1|Phase 2
NCT02579226 Recruiting Advanced Solid Tumours AstraZeneca October 28 2015 Phase 1
NCT02579226 Recruiting Advanced Solid Tumours AstraZeneca October 28 2015 Phase 1

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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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.

Aurora Kinase Signaling Pathway Map

Aurora Kinase Inhibitors with Unique Features

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID