Cat. No.: HY-18174

Prexasertib

(Synonyms: LY2606368)

36 Cited Publications

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Based on 36 publication(s) in Google Scholar

Prexasertib (LY2606368) is a selective, ATP-competitive second-generation checkpoint kinase 1 (CHK1) inhibitor with a K_i of 0.9 nM and an IC₅₀ of <1 nM. Prexasertib inhibits CHK2 (IC₅₀=8 nM) and RSK1 (IC₅₀=9 nM). Prexasertib causes double-stranded DNA breakage and replication catastrophe resulting in apoptosis. Prexasertib shows potent anti-tumor activity.

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Pureté: 99.64%
CAS No.: 1234015-52-1
Formule: C₁₈H₁₉N₇O₂
Masse moléculaire:365.39

Stockage:

Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 2 years , -20°C, 1 year

Prexasertib Chemical Structure

CAS No.: 1234015-52-1

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Activité biologique
- Description
- IC₅₀ & Target
- Cellular Effect
- In Vitro
- In Vivo
Chemical Information
Publications (36)
Solvant et solubilité
- In Vitro
- In Vivo
Pureté et documentation
Références
Help & FAQs
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Activité biologique

Description

IC₅₀ & Target^[1]

Chk1

0.9 nM (Ki)

Chk1

<1 nM (IC₅₀)

Chk2

8 nM (IC₅₀)

Voir tous les produits spécifiques à Isoform Checkpoint Kinase (Chk) :

Cellular Effect

Cell Line	Type	Value	Description	References
A2780	IC₅₀	40 nM Compound: Chemical probe: LY2606368	Cytotoxicity against human A2780 cells assessed as reduction in cell viability after 3 days by XTT assay Cytotoxicity against human A2780 cells assessed as reduction in cell viability after 3 days by XTT assay	[PMID: 28881656]
CHO	IC₅₀	20 μM Compound: 4; LY2606368	Inhibition of human ERG expressed in CHO cells at -80 mV holding potential by automated patch clamp assay Inhibition of human ERG expressed in CHO cells at -80 mV holding potential by automated patch clamp assay	[PMID: 30986571]
HEK293	IC₅₀	385.98 nM Compound: 4; LY2606368	Inhibition of recombinant human C-terminal His-tagged FLT3 (M1 to N541 residues) expressed in HEK293 cells using biotin-labelled STK substrate-1 as substrate incubated for 60 mins by HTRF assay Inhibition of recombinant human C-terminal His-tagged FLT3 (M1 to N541 residues) expressed in HEK293 cells using biotin-labelled STK substrate-1 as substrate incubated for 60 mins by HTRF assay	[PMID: 30986571]
JeKo-1	IC₅₀	0.004 μM Compound: 4; LY2606368	Inhibition of human JeKo1 cells incubated for 72 hrs by cellTiter 96 aqueous one solution reagent based assay Inhibition of human JeKo1 cells incubated for 72 hrs by cellTiter 96 aqueous one solution reagent based assay	[PMID: 30986571]
MV4-11	IC₅₀	0.004 μM Compound: 4; LY2606368	Inhibition of human MV411 cells incubated for 72 hrs by cellTiter 96 aqueous one solution reagent based assay Inhibition of human MV411 cells incubated for 72 hrs by cellTiter 96 aqueous one solution reagent based assay	[PMID: 30986571]
OVCAR-3	IC₅₀	12 nM Compound: Chemical probe: LY2606368	Cytotoxicity against human OVCAR-3 cells assessed as reduction in cell viability after 3 days by XTT assay Cytotoxicity against human OVCAR-3 cells assessed as reduction in cell viability after 3 days by XTT assay	[PMID: 28881656]
OVCAR-5	IC₅₀	3 nM Compound: Chemical probe: LY2606368	Cytotoxicity against human OVCAR-5 cells assessed as reduction in cell viability after 3 days by XTT assay Cytotoxicity against human OVCAR-5 cells assessed as reduction in cell viability after 3 days by XTT assay	[PMID: 28881656]
OVCAR-8	IC₅₀	10 nM Compound: Chemical probe: LY2606368	Cytotoxicity against human OVCAR-8 cells assessed as reduction in cell viability after 3 days by XTT assay Cytotoxicity against human OVCAR-8 cells assessed as reduction in cell viability after 3 days by XTT assay	[PMID: 28881656]
Ramos	IC₅₀	0.004 μM Compound: 4; LY2606368	Inhibition of human Ramos cells incubated for 72 hrs by cellTiter 96 aqueous one solution reagent based assay Inhibition of human Ramos cells incubated for 72 hrs by cellTiter 96 aqueous one solution reagent based assay	[PMID: 30986571]
RPMI-8226	IC₅₀	0.048 μM Compound: 4; LY2606368	Inhibition of human RPMI8226 cells incubated for 72 hrs by cellTiter 96 aqueous one solution reagent based assay Inhibition of human RPMI8226 cells incubated for 72 hrs by cellTiter 96 aqueous one solution reagent based assay	[PMID: 30986571]
SK-OV-3	IC₅₀	10 nM Compound: Chemical probe: LY2606368	Cytotoxicity against human SK-OV-3 cells assessed as reduction in cell viability after 3 days by XTT assay Cytotoxicity against human SK-OV-3 cells assessed as reduction in cell viability after 3 days by XTT assay	[PMID: 28881656]
Z-138	IC₅₀	0.033 μM Compound: 4; LY2606368	Inhibition of human Z138 cells incubated for 72 hrs by cellTiter 96 aqueous one solution reagent based assay Inhibition of human Z138 cells incubated for 72 hrs by cellTiter 96 aqueous one solution reagent based assay	[PMID: 30986571]

In Vitro

Prexasertib (LY2606368) inhibits MELK (IC₅₀=38 nM), SIK (IC₅₀=42 nM), BRSK2 (IC₅₀=48 nM), ARK5 (IC₅₀=64 nM). LY2606368 requires CDC25A and CDK2 to cause DNA damage^[1].
Prexasertib (33, 100 nM; for 7 hours) results in DNA damage during S-phase in HeLa cells^[1].
Prexasertib (8-250 nM; pre-treated for 15 minutes) inhibits CHK1 autophosphorylation (S296) and CHK2 autophosphorylation (S516) in HT-29 cells^[1].
Prexasertib (4 nM; 24 hours) results in a large shift in cell-cycle populations from G1 and G2-M to S-phase with an accompanied induction of H2AX phosphorylation in U-2 OS cells^[1].
Prexasertib (33 nM; for 12 hours) causes chromosomal fragmentation in HeLa cells. Prexasertib (100 nM; 0.5 to 9 hours) induces replication stress and depletes the pool of available RPA2 for binding to DNA^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Cycle Analysis^[1]

Cell Line:

HeLa cells
Concentration:

33, 100 nM
Incubation Time:

For 7 hours
Result:

Had an IC₅₀ of 37 nM and resulted in the G2-M population received DNA damage during S-phase but continued to progress through the cell cycle into an early mitosis.

Western Blot Analysis^[1]

Cell Line:

HT-29 cells
Concentration:

8, 16, 31, 63, 125, 250 nM
Incubation Time:

Pre-treated for 15 minutes
Result:

Inhibited CHK1 autophosphorylation (S296) and CHK2 autophosphorylation (S516) (IC₅₀ of less than 31 nM) in HT-29 cells.

In Vivo

Prexasertib (LY2606368; 1-10 mg/kg; SC; twice daily for 3 days, rest 4 days; for three cycles) causes growth inhibition in tumor xenografts^[1].
Prexasertib (15 mg/kg; SC) causes CHK1 inhibition in the blood and the phosphorylation of both H2AX (S139) and RPA2 (S4/S8)^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:

Female CD-1 nu-/nu- mice (26-28 g) with Calu-6 cells^[1]
Dosage:

1, 3.3, or 10 mg/kg
Administration:

SC; twice daily for 3 days, rest 4 days; for three cycles
Result:

Caused statistically significant tumor growth inhibition (up to 72.3%).

Animal Model:

Female CD-1 nu-/nu- mice (26-28 g) with Calu-6 cells^[1]
Dosage:

15 mg/kg (Pharmacokinetic Analysis)
Administration:

SC (200 μL)
Result:

CHK1 was 7 ng/mL at 12 hours and 3 ng/mL by 24 hours in plasma exposures.
Phosphorylation of both H2AX (S139) and RPA2 (S4/S8) was detectable at 4 hours, showing the rapid occurrence of DNA damage.

Chemical Information

CAS No. 1234015-52-1
Appearance Solid
Masse moléculaire 365.39
Formule C₁₈H₁₉N₇O₂
Color Light yellow to yellow
SMILES

NCCCOC(C=CC=C1OC)=C1C2=CC(NC3=NC=C(C#N)N=C3)=NN2
Synonyms

LY2606368
Livraison

Room temperature in continental US; may vary elsewhere.

Stockage

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	2 years
	-20°C	1 year

Publications (36)

All Cell Proliferation/Viability AssayWBFlow CytometryIn Vivo Efficacy StudyApoptosis AnalysisRT-PCR

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Journal Impact Factor

Nat Commun

MYC paralog-dependent apoptotic priming orchestrates a spectrum of vulnerabilities in small cell lung cancer. [Abstract]

2019 Aug 2;10(1):3485. PMID: 31375684

Prexasertib purchased from MedChemExpress. Usage Cited in: Nat Commun. 2019 Aug 2;10(1):3485. [Abstract]

Viability of mock control and Myc-activated CRISPRa cells upon treatment with 40 nM prexasertib for 96 h (n = 3).
Sci Adv

Patient-derived organoids across cancers reveal conserved tumor heterogeneity and actionable therapeutic vulnerabilities. [Abstract]

2026 Jun 26;12(26):eadz3351. PMID: 42361179
Cancer Lett

2026 Feb 4;642:218300.
Cancer Lett

Targeting ATR signaling in sarcoma with homologous recombination deficiency. [Abstract]

2026 Apr 1:642:218300. PMID: 41651400
Cell Death Dis

CHK1 is an integral regulator of DNA replication in human cells. [Abstract]

2026 Mar 26;17(1):375. PMID: 41888112
Thorax

Potential for inhibition of checkpoint kinases 1/2 in pulmonary fibrosis and secondary pulmonary hypertension. [Abstract]

2022 Mar;77(3):247-258. PMID: 34226205
Oncogene

DNA replication stress and translational repression converge to drive CDK1- and caspase-dependent apoptosis in Ewing sarcoma. [Abstract]

2026 Jun 10. PMID: 42270776
Oncogene

Distinct roles of treatment schemes and BRCA2 on the restoration of homologous recombination DNA repair and PARP inhibitor resistance in ovarian cancer. [Abstract]

2022 Nov;41(46):5020-5031. PMID: 36224341
Cell Rep

The low-dose CHK1 inhibitor prexasertib triggers VDAC1 dephosphorylation to activate mtDNA-STING signaling and synergize immunotherapy. [Abstract]

2025 Apr 17;44(5):115605. PMID: 40249707
Br J Cancer

Interferon regulatory factor 1 (IRF-1) downregulates Checkpoint kinase 1 (CHK1) through miR-195 to upregulate apoptosis and PD-L1 expression in Hepatocellular carcinoma (HCC) cells. [Abstract]

2021 Jul;125(1):101-111. PMID: 33772151

Prexasertib purchased from MedChemExpress. Usage Cited in: Br J Cancer. 2021 Jul;125(1):101-111. [Abstract]

Full length and cleaved PARP protein expressions are determined by western blot in Hepa1-6 cells and Huh-7 cells induced by prexasertib with dose of 1 µM and 5 nM for 24 h, respectively.

Prexasertib purchased from MedChemExpress. Usage Cited in: Br J Cancer. 2021 Jul;125(1):101-111. [Abstract]

Representative image of FACS analysis of late apoptotic Hepa1-6 cell rate treated by DMSO or prexasertib with dose of 1 µM for 24 h are shown.

Prexasertib purchased from MedChemExpress. Usage Cited in: Br J Cancer. 2021 Jul;125(1):101-111. [Abstract]

Tumour growth curves (Mean ± SEM) of murine HCC model treated by vehicle (n = 8) or prexasertib (10mg/kg, subcutaneous injection, 2 of 7 days, n = 8) are shown.

Prexasertib purchased from MedChemExpress. Usage Cited in: Br J Cancer. 2021 Jul;125(1):101-111. [Abstract]

Prexasertib (10mg/kg, subcutaneous injection, 2 of 7 days). Representative images of TUNEL assay for cellular apoptosis (green staining) in tumours are shown.

Prexasertib purchased from MedChemExpress. Usage Cited in: Br J Cancer. 2021 Jul;125(1):101-111. [Abstract]

Prexasertib (10mg/kg, subcutaneous injection, 2 of 7 days, n = 8). PD-L1 mRNA expression is determined by qPCR in tumours treated by prexasertib or vehicle.
Oncogenesis

STAG2 expression imparts distinct therapeutic vulnerabilities in muscle-invasive bladder cancer cells. [Abstract]

2025 Mar 1;14(1):4. PMID: 40025053
Cell Biol Toxicol

Exploring the ATR-CHK1 pathway in the response of doxorubicin-induced DNA damages in acute lymphoblastic leukemia cells. [Abstract]

2023 Jun;39(3):795-811. PMID: 34519926
Mol Cancer Ther

Targeting Monounsaturated Fatty Acid Metabolism for Radiosensitization of KRAS Mutant 3D Lung Cancer Models. [Abstract]

2025 Jun 4;24(6):920-930. PMID: 39834305
Cells

Genomic Engineering of Oral Keratinocytes to Establish In Vitro Oral Potentially Malignant Disease Models as a Platform for Treatment Investigation. [Abstract]

2024 Apr 19;13(8):710. PMID: 38667326
Int Immunopharmacol

CHK1 inhibition by prexasertib sensitizes cisplatin-resistant malignant tumor cells via checkpoint abrogation and STAT1-driven PD-L1 upregulation. [Abstract]

2025 Dec 31:171:116126. PMID: 41477994
Eur J Pharmacol

VOPP1, a determinant of the sensitivity of non-small cell lung cancer cells to NAE inhibitors. [Abstract]

2025 Sep 15:1003:177942. PMID: 40651787
Int Immunopharmacol

Prexasertib exerts a synergistic effect on the antitumor activity of Lenvatinib through ALOX15-mediated ferroptosis in hepatocellular carcinoma. [Abstract]

2025 Mar 26:150:114278. PMID: 39954659
Mol Cancer Res

Pharmacologic Ascorbate Primes Pancreatic Cancer Cells for Death by Rewiring Cellular Energetics and Inducing DNA Damage. [Abstract]

2019 Oct;17(10):2102-2114. PMID: 31337671
Cancers (Basel)

Novel Insights into the Molecular Regulation of Ribonucleotide Reductase in Adrenocortical Carcinoma Treatment. [Abstract]

2021 Aug 20;13(16):4200. PMID: 34439352
Cancers

Systems Biology Approach Identifies Prognostic Signatures of Poor Overall Survival and Guides the Prioritization of Novel BET-CHK1 Combination Therapy for Osteosarcoma. [Abstract]

2020 Aug 26;12(9):2426. PMID: 32859084
Cancers

Cotargeting CHK1 and PI3K Synergistically Suppresses Tumor Growth of Oral Cavity Squamous Cell Carcinoma in Patient-Derived Xenografts. [Abstract]

2020 Jun 29;12(7):1726. PMID: 32610557
Neurooncol Adv

Ion channel modulator DPI-201-106 significantly enhances antitumor activity of DNA damage response inhibitors in glioblastoma. [Abstract]

2024 Nov 19;6(1):vdae187. PMID: 39659830
Sci Rep

Synergistic inhibition of CHK1 and MUS81 to combat replication stress resistance in high-risk neuroblastoma. [Abstract]

2025 Nov 27. PMID: 41310217
Sci Rep

The mitotic checkpoint is a targetable vulnerability of carboplatin-resistant triple negative breast cancers. [Abstract]

2021 Feb 4;11(1):3176. PMID: 33542435
Cell Signal

MYC amplification sensitizes TNBC to CHK1 inhibitors. [Abstract]

2025 Jul:131:111709. PMID: 40037423
bioRxiv

2025 Dec 25.
bioRxiv

2025 April 17.
bioRxiv

PAIRWISE: Deep Learning-based Prediction of Effective Personalized Drug Combinations in Cancer. [Abstract]

2024 Nov 6:2024.11.04.621884. PMID: 39574568
Research Square Preprint

2024 Nov 06.
Universität Hamburg

2022 Aug.
Utrecht University

2023 Feb.
bioRxiv

January 04, 2022.
Patent

US20210353605A1.
bioRxiv

September 10, 2021.
Research Square Preprint

2021 May.
Methods Mol Biol

Methods for High-throughput Drug Combination Screening and Synergy Scoring. [Abstract]

2018:1711:351-398. PMID: 29344898

Solvant et solubilité

In Vitro:

DMSO : 16.67 mg/mL (45.62 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

View the Complete Stock Solution Preparation Table

Preparing Stock Solutions

View the Complete Stock Solution Preparation Table

Concentration Solvent Mass

1 mg

5 mg

10 mg

Concentration

Solvent

Mass

1 mM

2.7368 mL

13.6840 mL

27.3680 mL

5 mM

0.5474 mL

2.7368 mL

5.4736 mL

10 mM

0.2737 mL

1.3684 mL

2.7368 mL

Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.

Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

Calculateur de molarité

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass Mass

Concentration Concentration

Volume Volume

Molecular Weight Molecular Weight

Calculateur de dilution

Concentration _(start) × Volume _(start) = Concentration _(final) × Volume _(final)

Concentration _(start) Concentration _(start)

Volume _(start) Volume _(start)

Concentration _(final) Concentration _(final)

Volume _(final) Volume _(final)

In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

Stock Solution Working Solution

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

Protocol 1

Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline

Solubility: ≥ 1.67 mg/mL (4.57 mM); Clear solution

This protocol yields a clear solution of ≥ 1.67 mg/mL (saturation unknown).

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (16.7 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage Dosage
mg/kg
Animal Weight (Per Animal) Animal Weight (Per Animal)
g
Dosing Volume (Per Animal) Dosing Volume (Per Animal)
μL
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Please enter your animal formula composition:

%
DMSO +

Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
%
+
+
%
Tween-80 + +
%
Saline +

The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).

Working solution concentration: 0.22 mg/mL

Pureté et documentation

Select Batch:

Pureté: 99.98%

Assay: 99.98%

ee.: 99.98%

Fiche technique (285 KB)
SDS (393 KB)
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COA (2659 KB)
Elemental Analysis Report (2659 KB)
HNMR (2659 KB)
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Références

[1]. King C, et al. LY2606368 Causes Replication Catastrophe and Antitumor Effects through CHK1-Dependent Mechanisms. Mol Cancer Ther. 2015 Sep;14(9):2004-1 [Content Brief]

[2]. Yin Y, et al. Chk1 inhibition potentiates the therapeutic efficacy of PARP inhibitor BMN673 in gastric cancer. Am J Cancer Res. 2017 Mar 1;7(3):473-483. [Content Brief]

Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

Complete Stock Solution Preparation Table

Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

Optional Solvent	Concentration Solvent Mass	1 mg	5 mg	10 mg	25 mg
DMSO	1 mM	2.7368 mL	13.6840 mL	27.3680 mL	68.4200 mL
	5 mM	0.5474 mL	2.7368 mL	5.4736 mL	13.6840 mL
	10 mM	0.2737 mL	1.3684 mL	2.7368 mL	6.8420 mL
	15 mM	0.1825 mL	0.9123 mL	1.8245 mL	4.5613 mL
	20 mM	0.1368 mL	0.6842 mL	1.3684 mL	3.4210 mL
	25 mM	0.1095 mL	0.5474 mL	1.0947 mL	2.7368 mL
	30 mM	0.0912 mL	0.4561 mL	0.9123 mL	2.2807 mL
	40 mM	0.0684 mL	0.3421 mL	0.6842 mL	1.7105 mL

Prexasertib

36 Cited Publications

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Prexasertib

Apoptosis Compound Library

Cell Cycle/DNA Damage Compound Library

Kinase Inhibitor Library

Anti-Cancer Compound Library

Anti-Aging Compound Library

Anti-Prostate Cancer Compound Library

Cancer Stem Cells Compound Library

Heterocyclic Compound Library

Highly Selective Inhibitors Library

Highly Selective Activators Library

Cell Death Library

Serine/Threonine Kinase Inhibitor Library

Multi-Target Compound Library

Bioactive Compound Library Max

Anti-Aging Compound Library Mini

Kinase Inhibitor Library Mini

MCE Bioactive Compound Library

Bioactive Compound Library

Non-Alcoholic Fatty Liver Disease (NAFLD) Compound Library

High-Throughput Bioactive Compound Library

Posttranslational Modification Library

Publications Citing Use of MedChemExpress (MCE) Prexasertib

Voir tous les produits spécifiques à Isoform Checkpoint Kinase (Chk)

Activité biologique

Chemical Information

Publications (36)

Solvant et solubilité

Pureté et documentation

Références

Help & FAQs

Complete Stock Solution Preparation Table

Prexasertib

Apoptosis Compound Library

Cell Cycle/DNA Damage Compound Library

Kinase Inhibitor Library

Anti-Cancer Compound Library

Anti-Aging Compound Library

Anti-Prostate Cancer Compound Library

Cancer Stem Cells Compound Library

Heterocyclic Compound Library

Highly Selective Inhibitors Library

Highly Selective Activators Library

Cell Death Library

Serine/Threonine Kinase Inhibitor Library

Multi-Target Compound Library

Bioactive Compound Library Max

Anti-Aging Compound Library Mini

Kinase Inhibitor Library Mini

MCE Bioactive Compound Library

Bioactive Compound Library

Non-Alcoholic Fatty Liver Disease (NAFLD) Compound Library

High-Throughput Bioactive Compound Library

Posttranslational Modification Library

Publications Citing Use of MedChemExpress (MCE) Prexasertib

Voir tous les produits spécifiques à Isoform Checkpoint Kinase (Chk)

Activité biologique

Chemical Information

Publications (36)

Solvant et solubilité

Pureté et documentation

Références

Help & FAQs

Complete Stock Solution Preparation Table

Prexasertib Related Classifications

Cat. No.: HY-18174