Prexasertib HCl (LY2606368)

Catalog No.S7178

For research use only.

Prexasertib (LY2606368) is an ATP-competitive CHK1 inhibitor with a Ki value of 0.9 nmol/L. For CHK2 and RSK, its IC50 values are 8 nM and 9 nM respectively in cell-free assay.

Prexasertib HCl (LY2606368) Chemical Structure

CAS No. 1234015-54-3

Selleck's Prexasertib HCl (LY2606368) has been cited by 28 publications

Purity & Quality Control

Choose Selective Chk Inhibitors

Other Chk Products

Biological Activity

Description Prexasertib (LY2606368) is an ATP-competitive CHK1 inhibitor with a Ki value of 0.9 nmol/L. For CHK2 and RSK, its IC50 values are 8 nM and 9 nM respectively in cell-free assay.
Targets
Chk1 [1]
(Cell-free assay)
Chk2 [1]
(Cell-free assay)
RSK [1]
(Cell-free assay)
0.9 nM(Ki) 8 nM 9 nM
In vitro

In nonclinical studies, LY2606368 induced DNA damage as measured by replication catastrophe and increases in pH2A.X, a marker of double-stranded DNA breaks[1]. Treatment of cells with LY2606368 results in the rapid appearance of TUNEL and pH2AX-positive double-stranded DNA breaks in the S-phase cell population. In a functional assay, LY2606368 potently abrogated the G2–M checkpoint activated by doxorubicin in p53-deficient HeLa cells with an EC50 of 9 nmol/L. LY2606368 was broadly antiproliferative with IC50 values typically <50 nmol/L in the most sensitive cell lines with a minority of cell lines showing considerable resistance with IC50's >1,000 nmol/L. LY2606368 requires CDC25A and CDK2 to cause DNA damage[2].

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
HeLa cells MYLGeY5kfGmxbjDhd5NigQ>? M2TyelM{KG:{IEGwNEBvdW:uL1y= MXm3JIhwfXK| MXjifUA4KGixdYLzMEBiKHO3YoDvdJVt[XSrb36gc4Yh[2WubIOgd5RicW6nZDDzeJJwdmeueTDmc5IhTFOEIHL5JIJwfGhiVGXOSWwh[W6mIIDINmFZ NHnaW2M9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NkG0NVk1QCd-Mk[xOFE6PDh:L3G+
U-2 OS cells NXrTW2R7TnWwY4Tpc44h[XO|YYm= NVHLZXlYPCCwbX;sM2w> MXSyOEBp M{\NTYEhdGG{Z3Wgd4hq\nRiaX6gZ4VtdC2leXPs[UBxd3C3bHH0bY9veyCocn;tJGcyKGGwZDDHNwKBm01idH:gV{1xcGG|ZTD3bZRpKGGwIHHjZ49ueGGwaXXkJIlv\HWldHnvckBw\iCKMlHYJJBpd3OyaH;yfYxifGmxbj6= NXfWbHQ2RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[xOFE6PDhpPkK2NVQyQTR6PD;hQi=>
CCRF-CEM parental cells Mn7OSpVv[3Srb36gZZN{[Xl? NGK4blUyOCCwTR?= NGLNcGw1KGh? NULWSZpPcW6mdXPl[EBUVE[QMUGgZolv\GmwZzD0c{BkcHKxbXH0bY4h[W6mIHnuZ5Jm[XOnZDD0bIUh[2i{b33heIlvKGKrbnTpcochd2ZiQ1TDOFU> M{H4blxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7M{m1NFYyLz5{OUO5OVA3OTxxYU6=
SLFN11-del cells MY\GeY5kfGmxbjDhd5NigQ>? MlfFNVAhdk1? NUDJWZJXPCCq Ml\QbY5lfWOnZDDTUGZPOTFiYnnu[Ilv\yC2bzDjbJJwdWG2aX6gZY5lKGmwY4LlZZNm\CC2aHWgZ4hzd22jdHnuJIJqdmSrbnegc4YhS0SFNEW= NXiwZ41oRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkmzPVUxPjFpPkK5N|k2ODZzPD;hQi=>
K562-WT M1\XPGZ2dmO2aX;uJIF{e2G7 MX6xNFAhdk1? MYiyJIg> NUG1WYNPW0yITkGxMEBETEN2NTDhcoQhWEOQQTD3[ZJmKGWwcnnjbIVlKG:wIH7hd4NmdnRiRF7B M2rWVFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7M{m1NFYyLz5{OUO5OVA3OTxxYU6=
K562-E669Q NGHDSolHfW6ldHnvckBie3OjeR?= MlXxNVAxKG6P NFnLfZozKGh? M3nhU3NNTk5zMTygR2REPDViYX7kJHBEVkFid3Xy[UBmdnKrY3jl[EBwdiCwYYPj[Y51KESQQR?= MVS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTN7NUC2NUc,Ojl|OUWwOlE9N2F-
CCRF-CEM parental cells M3v1ZWZ2dmO2aX;uJIF{e2G7 M2O3fFExOCCwTR?= NHzUSW8zKGh? MlW5V2xHVjFzLDDDSGM1PSCjbnSgVGNPSSC5ZYLlJIVvemmlaHXkJI9vKG6jc3PlcpQhTE6D M1zZRVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7M{m1NFYyLz5{OUO5OVA3OTxxYU6=
HCT-116 cells NGWz[ZZHfW6ldHnvckBie3OjeR?= MXexNQKBt2SjeYO= NGLsU5lqdmirYnn0[YQh[m:2aDDGRW5ETDJidXLpdZVqfGmwYYTpc44h[W6mIHnuZ5Jm[XOnZDDSZYQ2OSCuZY\lcJMtKHOrZ37p[olk[W62bImgbY5kemWjc3XkJJNmdnOrdHn2bZR6KG:oIFjDWE0yOTZiY3XscJMhfG9iRkGw MoDXQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOzB2M{m1OlcoRjNyNEO5OVY4RC:jPh?=
U937 cells M4PuZ2Z2dmO2aX;uJIF{e2G7 MkO5N-KBkW6P MmPL[Y5p[W6lZXSgeIhmKGO7dH;0c5hq[2m2eTDv[kBEWFhvM{WxJIF1KGyxdzDuZY5wdW:uYYKgZ49v[2WwdILheIlwdnN? NXT0bos1RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxM{C4N|c3PDNpPkOwPFM4PjR|PD;hQi=>
KB-3-1 MkjqSpVv[3Srb36gZZN{[Xl? MmfqVE1odHmlb4Dyc5RmcW5ic4Xid5Rz[XSnczDp[IVvfGmoaXXkJIlvKEuELUOtNUBi\GWwb3PhdoNqdm:vYTDj[YxtKGyrbnWsJJFJXFNidHjldoFx\XW2aXOgcIljemG{eTDzZ5Jm\W5? NGXFRoo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9|MUWxOVI5PCd-M{G1NVUzQDR:L3G+
KB-8-5-11 NYW0Z2VpTnWwY4Tpc44h[XO|YYm= NEH1OYtRNWeueXPvdJJwfGWrbjDzeYJ{fHKjdHXzJIll\W62aX\p[YQhcW5iS1KtPE02NTFzIHHk[Y5w[2G{Y3nuc41iKGOnbHygcIlv\SxicVjUV{B1cGW{YYDleZRq[yCuaXLyZZJ6KHOlcnXlckwhWG:2ZX7jfUA:KDFwMkm5OUDPxE1w M1X0XVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzNzNUG1Nlg1Lz5|MUWxOVI5PDxxYU6=
Assay
Methods Test Index PMID
Western blot CHK1 / p-CHK1(Ser345) / γH2AX / Cleaved caspase3 ; pS6 (S235/236) / pS6 (S240/244) 28401005 28490518
Immunofluorescence SLFN11 / CDC45 / EdU 29395061
Growth inhibition assay Cell viability ; IC50 28401005 28490518
In vivo LY2606368 inhibited tumor growth in cancer xenografts as monotherapy and in combination with other agents[1]. In an orthotopic SKOV3 ovarian cancer model, LY2606368 was shown to inhibit the growth of primary tumors and significantly reduce the incidence of metastases and ascites accumulation. LY2606368 also demonstrated efficacy in an SW1990 orthotopic pancreatic cancer model resulting in a 92% inhibition of primary tumor growth and the elimination of metastases to the lymphnode, spleen, and intestine[3].

Protocol (from reference)

Cell Research:

[2]

  • Cell lines: HeLa cells
  • Concentrations: 33 or 100 nmol/L
  • Incubation Time: 12 h
  • Method:

    HeLa cells were plated onto T25 flasks and allowed to recover for 24 hours. LY2606368 was then added to give final concentrations of 33 or 100 nmol/L. In some experiments, 20μmol/L Z-VAD-FMK was included during the drug treatment. Cells were treated for 12 hours, and during the last 2 hours, colchicine was added to 1 μg/mL. Fixation of nuclei for metaphase spreads was done following the method of Bayani and Squire. Chromosome spreads were done. A 12-μL volume of cell suspension in 3:1 methanol/acetic acid fixative was dropped from a height of 3 cm onto dry glass slides or coverslips. The slides were then heated for 45 seconds on a 43°C metal block, before being removed to allow drying to complete at room temperature. Coverslips were mounted on slides with Vectashield Hard Set mounting medium with DAPI. Slides were examined with a Leica DMR fluorescence microscope and images were captured using a SPOT RT3 Slider camera.

Animal Research:

[2]

  • Animal Models: Female CD-1 nu-/nu- mice
  • Dosages: 15 mg/kg
  • Administration: s.c.

Solubility (25°C)

In vitro

Chemical Information

Molecular Weight 438.31
Formula

C18H19N7O2.2HCl

CAS No. 1234015-54-3
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles COC1=C(C(=CC=C1)OCCCN)C2=CC(=NN2)NC3=NC=C(N=C3)C#N.Cl.Cl

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

mg/kg g μL

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Molarity Calculator

Mass Concentration Volume Molecular Weight

Clinical Trial Information

NCT Number Recruitment Interventions Conditions Sponsor/Collaborators Start Date Phases
NCT04095221 Active not recruiting Drug: Prexasertib|Drug: Irinotecan Desmoplastic Small Round Cell Tumor|Rhabdomyosarcoma Memorial Sloan Kettering Cancer Center September 17 2019 Phase 1|Phase 2
NCT03495323 Completed Drug: LY3300054|Drug: Prexasertib Cancer Dana-Farber Cancer Institute|Eli Lilly and Company May 16 2018 Phase 1
NCT03414047 Completed Drug: Prexasertib Ovarian Cancer Eli Lilly and Company April 10 2018 Phase 2
NCT03057145 Completed Drug: Prexasertib|Drug: Olaparib Solid Tumor Geoffrey Shapiro MD PhD|Eli Lilly and Company|AstraZeneca|Dana-Farber Cancer Institute March 10 2017 Phase 1

(data from https://clinicaltrials.gov, updated on 2022-08-01)

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

Tel: +1-832-582-8158 Ext:3
If you have any other enquiries, please leave a message.

* Indicates a Required Field

Please enter your name.
Please enter your email. Please enter a valid email address.
Please write something to us.

Frequently Asked Questions

Question 1:
Would you please suggest a suitable vehicle to dissolve Prexasertib HCl (LY2606368) for in vivo use?

Answer:
You can dissolve S7178 in a vehicle: 5% DMSO+40%PEG 300+5%Tween80+ddH2O for in vivo use in mice (i.p.). This stock concentration reahces 10mg/ml, and can be prepared for work solution as 0.5mg/ml, stable for no longer than 30min.

Question 2:
What is the solubility of LY2606368 in 20% Captisol?

Answer:
S7178 in 20% Captisol is a suspension, which is fine for oral gavage. You can dissolve it in this vehicle to the concentration you need as long as the suspension is homogeneous.

Tags: buy Prexasertib HCl (LY2606368) | Prexasertib HCl (LY2606368) supplier | purchase Prexasertib HCl (LY2606368) | Prexasertib HCl (LY2606368) cost | Prexasertib HCl (LY2606368) manufacturer | order Prexasertib HCl (LY2606368) | Prexasertib HCl (LY2606368) distributor