| Field | Specification |
|---|---|
| Target | |
| Alternative names | LY2606368 dihydrochloride |
| CAS no. | |
| Applications | |
| Molecular weight | |
| Molecular formula | C18H21Cl2N7O2 |
| Purity | |
| SMILES | |
| Form | Solid |
| Storage | |
| Shipping | |
| Catalog no. (Mfr.) | |
| Main SKU |
Compound Overview
Prexasertib dihydrochloride, also known as LY2606368 dihydrochloride, is a selective, ATP-competitive second-generation inhibitor of checkpoint kinase 1 (CHK1), with a Ki of 0.9 nM and an IC50 below 1 nM. It also inhibits CHK2 (IC50 = 8 nM) and RSK1 (IC50 = 9 nM), and it causes double-stranded DNA breakage and replication catastrophe that results in apoptosis. The compound shows potent antitumor activity[1][2]. It is supplied as a light yellow to yellow solid (C18H21Cl2N7O2, MW 438.31) at 99.42% purity.
Physical & Chemical Properties
| CAS Number | 1234015-54-3 |
|---|---|
| Molecular Formula | C18H21Cl2N7O2 |
| Molecular Weight | 438.31 g/mol |
| Purity | 99.42% |
| Appearance | Solid |
| Color | Light yellow to yellow |
| SMILES | NCCCOC(C=CC=C1OC)=C1C2=CC(NC3=NC=C(C#N)N=C3)=NN2.[H]Cl.[H]Cl |
| Target | Chk1, Chk2 |
| Signaling Pathway | Cell Cycle/DNA Damage; Apoptosis |
| Solubility | In Vitro: DMSO: 8 mg/mL (18.25 mM; Requires sonication; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO) H2O: < 0.1 mg/mL (insoluble) |
| Storage | 4°C, sealed storage, away from moisture. In solvent: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture). |
| Shipping | Room temperature in continental US; may vary elsewhere. |
Biological Activity
IC50 & Target[1]
|
Chk1 0.9 nM (Ki) |
Chk1 <1 nM (IC50) |
Chk2 8 nM (IC50) |
Literature Cited
Sources cited in this description and in the In Vitro & In Vivo Data tab. Peer-reviewed publications that used this product are listed under References.
Safety
For Research Use Only. Not for use in diagnostic or therapeutic procedures, and not for human or veterinary use. Handle in accordance with the Safety Data Sheet and your institution's chemical hygiene plan.
In Vitro
| Solvent | Solubility | Notes |
|---|---|---|
| DMSO | 8 mg/mL (18.25 mM) | requires sonication; use freshly opened DMSO (absorbed moisture lowers solubility) |
| H2O | < 0.1 mg/mL | insoluble |
Aliquot the stock solution and store it at -80°C (up to 6 months) or -20°C (up to 1 month); sealed storage, away from moisture; avoid repeated freeze-thaw cycles.
If water is used as the stock solvent, dilute to the working solution and sterilize it through a 0.22 μm filter before use.
In Vivo
Choose the formulation that suits the animal model and route of administration; percentages are volume ratios of the final working solution. Start from a clear DMSO stock (see In Vitro above), add the co-solvents one at a time in the order listed, mixing after each addition, and prepare the working solution fresh on the day of dosing. If precipitation or phase separation occurs, gentle warming or sonication can help.
Protocol 1
| Composition | 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% saline |
|---|---|
| Result | ≥ 0.8 mg/mL (1.83 mM); clear solution |
| How to prepare | Gives a clear solution at ≥ 0.8 mg/mL (saturation not determined). For 1 mL of working solution: add 100 μL DMSO stock (8.0 mg/mL) to 400 μL PEG300; then 50 μL Tween-80; then 450 μL saline to bring the volume to 1 mL. Saline: dissolve 0.9 g sodium chloride in ddH2O and make up to 100 mL. |
Protocol 2
| Composition | 10% DMSO + 90% (20% SBE-β-CD in saline) |
|---|---|
| Result | ≥ 0.8 mg/mL (1.83 mM); clear solution |
| How to prepare | Gives a clear solution at ≥ 0.8 mg/mL (saturation not determined). For 1 mL of working solution: add 100 μL DMSO stock (8.0 mg/mL) to 900 μL 20% SBE-β-CD in saline. 20% SBE-β-CD in saline: dissolve 2 g SBE-β-CD powder in 10 mL saline until clear (4°C, store up to one week). |
Data provided by the manufacturer.
In Vitro
Prexasertib dihydrochloride (LY2606368 dihydrochloride) inhibits MELK, SIK, BRSK2, and ARK5, with IC50 values of 38 nM, 42 nM, 48 nM, and 64 nM, respectively. LY2606368 needs CDC25A and CDK2 to cause DNA damage[1]. In HeLa cells, Prexasertib dihydrochloride (33, 100 nM; for 7 hours) produces DNA damage during S-phase[1]. In HT-29 cells, Prexasertib dihydrochloride (8-250 nM; pre-treated for 15 minutes) blocks CHK1 autophosphorylation (S296) and CHK2 autophosphorylation (S516)[1]. In U-2 OS cells, Prexasertib dihydrochloride (4 nM; 24 hours) shifts cell-cycle populations substantially from G1 and G2-M into S-phase, accompanied by induction of H2AX phosphorylation[1]. In HeLa cells, Prexasertib dihydrochloride (33 nM; for 12 hours) causes chromosomal fragmentation. Replication stress is induced by Prexasertib (100 nM; 0.5 to 9 hours), which depletes the pool of RPA2 available for DNA binding[1].
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
Given SC at 1-10 mg/kg twice daily for 3 days with 4 days of rest, for three cycles, Prexasertib dihydrochloride (LY2606368 dihydrochloride) causes growth inhibition in tumor xenografts[1]. Prexasertib dihydrochloride (15 mg/kg; SC) inhibits CHK1 in the blood and induces phosphorylation of both H2AX (S139) and RPA2 (S4/S8)[1].
| 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. |
Data provided by the manufacturer. Numbered citations refer to the Literature Cited list in the product description.
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MYC paralog-dependent apoptotic priming orchestrates a spectrum of vulnerabilities in small cell lung cancer. Nat Commun 2019 Aug 2;10(1):3485.
Patient-derived organoids across cancers reveal conserved tumor heterogeneity and actionable therapeutic vulnerabilities. Sci Adv 2026 Jun 26;12(26):eadz3351. PMID: 42361179
CHK1 is an integral regulator of DNA replication in human cells. Cell Death Dis 2026 Mar 26;17(1):375. PMID: 41888112
Cancer Lett. 2026 Feb 4;642:218300.
Targeting ATR signaling in sarcoma with homologous recombination deficiency. Cancer Lett 2026 Apr 1:642:218300. PMID: 41651400
DNA replication stress and translational repression converge to drive CDK1- and caspase-dependent apoptosis in Ewing sarcoma. Oncogene 2026 Jun 10. PMID: 42270776
Distinct roles of treatment schemes and BRCA2 on the restoration of homologous recombination DNA repair and PARP inhibitor resistance in ovarian cancer. Oncogene 2022 Nov;41(46):5020-5031. PMID: 36224341
Potential for inhibition of checkpoint kinases 1/2 in pulmonary fibrosis and secondary pulmonary hypertension. Thorax 2022 Mar;77(3):247-258. PMID: 34226205
The cytotoxic effect of prexasertib is a consequence of dual inhibition on both CHK1 and AMPK. Cell Chem Biol 2026 Jun 18;33(6):767-784.e7. PMID: 42061410
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. Br J Cancer 2021 Jul;125(1):101-111. PMID: 33772151
