Prexasertib mesylate
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MedKoo CAT#: 206787

CAS#: 1234015-55-4 (mesylate)

Description: Prexasertib, also known as LY2606368, is a potent and selective Chk1/Chk2 inhibitor. Prexasertib increases the effectiveness of conventional therapy in B-/T- cell progenitor acute lymphoblastic leukemia. LY2606368 Causes Replication Catastrophe and Antitumor Effects through CHK1-Dependent Mechanisms. 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.


Chemical Structure

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Prexasertib mesylate
CAS# 1234015-55-4 (mesylate)

Theoretical Analysis

MedKoo Cat#: 206787
Name: Prexasertib mesylate
CAS#: 1234015-55-4 (mesylate)
Chemical Formula: C19H23N7O5S
Exact Mass: 0.00
Molecular Weight: 461.500
Elemental Analysis: C, 49.45; H, 5.02; N, 21.25; O, 17.33; S, 6.95

Price and Availability

Size Price Availability Quantity
10mg USD 150 Ready to ship
25mg USD 250 Ready to ship
50mg USD 450 Ready to ship
100mg USD 750 Ready to ship
200mg USD 1350 Ready to Ship
500mg USD 2850 Ready to Ship
1g USD 4350 Ready to Ship
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Related CAS #: 1234015-54-3 (2HCl)   1234015-55-4 (mesylate)   1234015-52-1 (free base)   1234015-57-6 (mesylate hydrate)    

Synonym: Prexasertib mesylate; LY2606368; LY-2606368; LY 2606368.

IUPAC/Chemical Name: 2-Pyrazinecarbonitrile, 5-((5-(2-(3-aminopropoxy)-6-methoxyphenyl)-1H-pyrazol-3-yl)amino)-, methanesulfonate

InChi Key: WGCKOJKXQKKLQW-UHFFFAOYSA-N

InChi Code: InChI=1S/C18H19N7O2.CH4O3S/c1-26-14-4-2-5-15(27-7-3-6-19)18(14)13-8-16(25-24-13)23-17-11-21-12(9-20)10-22-17;1-5(2,3)4/h2,4-5,8,10-11H,3,6-7,19H2,1H3,(H2,22,23,24,25);1H3,(H,2,3,4)

SMILES Code: N#CC1=NC=C(NC2=NNC(C3=C(OC)C=CC=C3OCCCN)=C2)N=C1.CS(=O)(O)=O

Appearance: Yellow solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

More Info:

Biological target: Prexasertib inhibits CHK1, CHK2, and RSK1 with IC50s of <1 nM, 8 nM, and 9 nM, respectively.
In vitro activity: The efficacy of the Checkpoint kinase 1/2 (Chk 1/2) inhibitor prexasertib mesylate in B-/T- cell progenitor acute lymphoblastic leukemia (ALL) was evaluated. Prexasertib reduced the cell viability in a dose and time dependent manner in all treated cell lines. The cytotoxic activity was confirmed by the increment of apoptotic cells (Annexin V/Propidium Iodide staining), by the increase of γH2A.X protein expression and by the activation of different apoptotic markers (Parp-1 and pro-Caspase3 cleavage). Furthermore, the inhibition of Chk1 changed the cell cycle profile. Prexasertib reduced the amount of cells in G1 and G2/M phase while increasing the number of cells in S phase. Reference: Oncotarget. 2016 Aug 16;7(33):53377-53391. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5288194/
In vivo activity: The antitumor efficacy of LY2606368 was investigated in a syngeneic flank tumor model generated from subcutaneous injection of cells (TKO.mTmG) derived from a GEMM (genetically engineered mouse model) with conditional loss of Trp53, p130, and Rb1 in the neuroendocrine cells of the lung (23, 24). These mice developed tumors that closely resembled human SCLC (small cell lung cancer). Tumor-bearing mice (n = 9 per group) were treated with LY2606368 or vehicle. Within 1 week of the start of treatment with LY2606368, remarkable tumor regression was observed (Fig. 3A; Supplementary Fig. S3B). Of the 9 mice treated with LY2606368 (10 mg/kg, twice daily, days 1–3 of a 7-day cycle; i.e., 60 mg/kg per week), 6 had a complete response (100% reduction) and the other 3 had >75% reduction in tumor volume. The tumor–control ratio at day 12 was 0.02 (P < 0.001). Mice treated with a lower dose of LY2606368 (16 mg/kg, twice daily, day 1 of a 7-day cycle; i.e., 32 mg/kg per week) had stable disease for up to 30 days, with a tumor–control ratio of 0.16 (P < 0.001; Fig. 3A; Supplementary Fig. S3B). In contrast, all vehicle-treated mice (n = 9) experienced rapid tumor progression and were removed from the experiment because of excessive tumor volume within two weeks (Fig. 3A and B; Supplementary Fig. S3B). Reference: Cancer Res. 2017 Jul 15;77(14):3870-3884. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5563854/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 24.0 52.00

Preparing Stock Solutions

The following data is based on the product molecular weight 461.50 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Ghelli Luserna Di Rorà A, Iacobucci I, Imbrogno E, Papayannidis C, Derenzini E, Ferrari A, Guadagnuolo V, Robustelli V, Parisi S, Sartor C, Abbenante MC, Paolini S, Martinelli G. Prexasertib, a Chk1/Chk2 inhibitor, increases the effectiveness of conventional therapy in B-/T- cell progenitor acute lymphoblastic leukemia. Oncotarget. 2016 Aug 16;7(33):53377-53391. doi: 10.18632/oncotarget.10535. PMID: 27438145; PMCID: PMC5288194. 2. Brill E, Yokoyama T, Nair J, Yu M, Ahn YR, Lee JM. Prexasertib, a cell cycle checkpoint kinases 1 and 2 inhibitor, increases in vitro toxicity of PARP inhibition by preventing Rad51 foci formation in BRCA wild type high-grade serous ovarian cancer. Oncotarget. 2017 Oct 31;8(67):111026-111040. doi: 10.18632/oncotarget.22195. PMID: 29340034; PMCID: PMC5762302. 3. Zeng L, Nikolaev A, Xing C, Della Manna DL, Yang ES. CHK1/2 Inhibitor Prexasertib Suppresses NOTCH Signaling and Enhances Cytotoxicity of Cisplatin and Radiation in Head and Neck Squamous Cell Carcinoma. Mol Cancer Ther. 2020 Jun;19(6):1279-1288. doi: 10.1158/1535-7163.MCT-19-0946. Epub 2020 May 5. PMID: 32371584. 4. Sen T, Tong P, Stewart CA, Cristea S, Valliani A, Shames DS, Redwood AB, Fan YH, Li L, Glisson BS, Minna JD, Sage J, Gibbons DL, Piwnica-Worms H, Heymach JV, Wang J, Byers LA. CHK1 Inhibition in Small-Cell Lung Cancer Produces Single-Agent Activity in Biomarker-Defined Disease Subsets and Combination Activity with Cisplatin or Olaparib. Cancer Res. 2017 Jul 15;77(14):3870-3884. doi: 10.1158/0008-5472.CAN-16-3409. Epub 2017 May 10. PMID: 28490518; PMCID: PMC5563854.
In vitro protocol: 1. Ghelli Luserna Di Rorà A, Iacobucci I, Imbrogno E, Papayannidis C, Derenzini E, Ferrari A, Guadagnuolo V, Robustelli V, Parisi S, Sartor C, Abbenante MC, Paolini S, Martinelli G. Prexasertib, a Chk1/Chk2 inhibitor, increases the effectiveness of conventional therapy in B-/T- cell progenitor acute lymphoblastic leukemia. Oncotarget. 2016 Aug 16;7(33):53377-53391. doi: 10.18632/oncotarget.10535. PMID: 27438145; PMCID: PMC5288194. 2. Brill E, Yokoyama T, Nair J, Yu M, Ahn YR, Lee JM. Prexasertib, a cell cycle checkpoint kinases 1 and 2 inhibitor, increases in vitro toxicity of PARP inhibition by preventing Rad51 foci formation in BRCA wild type high-grade serous ovarian cancer. Oncotarget. 2017 Oct 31;8(67):111026-111040. doi: 10.18632/oncotarget.22195. PMID: 29340034; PMCID: PMC5762302.
In vivo protocol: 1. Zeng L, Nikolaev A, Xing C, Della Manna DL, Yang ES. CHK1/2 Inhibitor Prexasertib Suppresses NOTCH Signaling and Enhances Cytotoxicity of Cisplatin and Radiation in Head and Neck Squamous Cell Carcinoma. Mol Cancer Ther. 2020 Jun;19(6):1279-1288. doi: 10.1158/1535-7163.MCT-19-0946. Epub 2020 May 5. PMID: 32371584. 2. Sen T, Tong P, Stewart CA, Cristea S, Valliani A, Shames DS, Redwood AB, Fan YH, Li L, Glisson BS, Minna JD, Sage J, Gibbons DL, Piwnica-Worms H, Heymach JV, Wang J, Byers LA. CHK1 Inhibition in Small-Cell Lung Cancer Produces Single-Agent Activity in Biomarker-Defined Disease Subsets and Combination Activity with Cisplatin or Olaparib. Cancer Res. 2017 Jul 15;77(14):3870-3884. doi: 10.1158/0008-5472.CAN-16-3409. Epub 2017 May 10. PMID: 28490518; PMCID: PMC5563854.

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1: Koppenhafer SL, Goss KL, Terry WW, Gordon DJ. mTORC1/2 and protein translation regulate levels of CHK1 and the sensitivity to CHK1 inhibitors in Ewing sarcoma cells. Mol Cancer Ther. 2018 Oct 3. pii: molcanther.0260.2018. doi: 10.1158/1535-7163.MCT-18-0260. [Epub ahead of print] PubMed PMID: 30282812.

2: Iwasa S, Yamamoto N, Shitara K, Tamura K, Matsubara N, Tajimi M, Lin AB, Asou H, Cai Z, Inoue K, Shibasaki Y, Saito K, Takai H, Doi T. Dose-finding study of the checkpoint kinase 1 inhibitor, prexasertib, in Japanese patients with advanced solid tumors. Cancer Sci. 2018 Oct;109(10):3216-3223. doi: 10.1111/cas.13750. PubMed PMID: 30040168.

3: Zhong B, Maharaj A, Davis A, Roussel MF, Stewart CF. Development and validation of a sensitive LC MS/MS method for the measurement of the checkpoint kinase 1 inhibitor prexasertib and its application in a cerebral microdialysis study. J Pharm Biomed Anal. 2018 Jul 15;156:97-103. doi: 10.1016/j.jpba.2018.04.018. Epub 2018 Apr 17. PubMed PMID: 29698863; PubMed Central PMCID: PMC5984718.

4: Hong DS, Moore K, Patel M, Grant SC, Burris HA 3rd, William WN Jr, Jones S, Meric-Bernstam F, Infante J, Golden L, Zhang W, Martinez R, Wijayawardana S, Beckmann R, Lin AB, Eng C, Bendell J. Evaluation of Prexasertib, a Checkpoint Kinase 1 Inhibitor, in a Phase Ib Study of Patients with Squamous Cell Carcinoma. Clin Cancer Res. 2018 Jul 15;24(14):3263-3272. doi: 10.1158/1078-0432.CCR-17-3347. Epub 2018 Apr 11. PubMed PMID: 29643063; PubMed Central PMCID: PMC6050086.

5: Murai J, Tang SW, Leo E, Baechler SA, Redon CE, Zhang H, Al Abo M, Rajapakse VN, Nakamura E, Jenkins LMM, Aladjem MI, Pommier Y. SLFN11 Blocks Stressed Replication Forks Independently of ATR. Mol Cell. 2018 Feb 1;69(3):371-384.e6. doi: 10.1016/j.molcel.2018.01.012. PubMed PMID: 29395061; PubMed Central PMCID: PMC5802881.

6: Lee JM, Nair J, Zimmer A, Lipkowitz S, Annunziata CM, Merino MJ, Swisher EM, Harrell MI, Trepel JB, Lee MJ, Bagheri MH, Botesteanu DA, Steinberg SM, Minasian L, Ekwede I, Kohn EC. Prexasertib, a cell cycle checkpoint kinase 1 and 2 inhibitor, in BRCA wild-type recurrent high-grade serous ovarian cancer: a first-in-class proof-of-concept phase 2 study. Lancet Oncol. 2018 Feb;19(2):207-215. doi: 10.1016/S1470-2045(18)30009-3. Epub 2018 Jan 18. PubMed PMID: 29361470.

7: Brill E, Yokoyama T, Nair J, Yu M, Ahn YR, Lee JM. Prexasertib, a cell cycle checkpoint kinases 1 and 2 inhibitor, increases in vitro toxicity of PARP inhibition by preventing Rad51 foci formation in BRCA wild type high-grade serous ovarian cancer. Oncotarget. 2017 Oct 31;8(67):111026-111040. doi: 10.18632/oncotarget.22195. eCollection 2017 Dec 19. PubMed PMID: 29340034; PubMed Central PMCID: PMC5762302.

8: Cole KP, Groh JM, Johnson MD, Burcham CL, Campbell BM, Diseroad WD, Heller MR, Howell JR, Kallman NJ, Koenig TM, May SA, Miller RD, Mitchell D, Myers DP, Myers SS, Phillips JL, Polster CS, White TD, Cashman J, Hurley D, Moylan R, Sheehan P, Spencer RD, Desmond K, Desmond P, Gowran O. Kilogram-scale prexasertib monolactate monohydrate synthesis under continuous-flow CGMP conditions. Science. 2017 Jun 16;356(6343):1144-1150. doi: 10.1126/science.aan0745. PubMed PMID: 28619938.

9: Sen T, Tong P, Stewart CA, Cristea S, Valliani A, Shames DS, Redwood AB, Fan YH, Li L, Glisson BS, Minna JD, Sage J, Gibbons DL, Piwnica-Worms H, Heymach JV, Wang J, Byers LA. CHK1 Inhibition in Small-Cell Lung Cancer Produces Single-Agent Activity in Biomarker-Defined Disease Subsets and Combination Activity with Cisplatin or Olaparib. Cancer Res. 2017 Jul 15;77(14):3870-3884. doi: 10.1158/0008-5472.CAN-16-3409. Epub 2017 May 10. PubMed PMID: 28490518; PubMed Central PMCID: PMC5563854.

10: Manic G, Signore M, Sistigu A, Russo G, Corradi F, Siteni S, Musella M, Vitale S, De Angelis ML, Pallocca M, Amoreo CA, Sperati F, Di Franco S, Barresi S, Policicchio E, De Luca G, De Nicola F, Mottolese M, Zeuner A, Fanciulli M, Stassi G, Maugeri-Saccà M, Baiocchi M, Tartaglia M, Vitale I, De Maria R. CHK1-targeted therapy to deplete DNA replication-stressed, p53-deficient, hyperdiploid colorectal cancer stem cells. Gut. 2018 May;67(5):903-917. doi: 10.1136/gutjnl-2016-312623. Epub 2017 Apr 7. PubMed PMID: 28389531; PubMed Central PMCID: PMC5890648.

11: Lowery CD, VanWye AB, Dowless M, Blosser W, Falcon BL, Stewart J, Stephens J, Beckmann RP, Bence Lin A, Stancato LF. The Checkpoint Kinase 1 Inhibitor Prexasertib Induces Regression of Preclinical Models of Human Neuroblastoma. Clin Cancer Res. 2017 Aug 1;23(15):4354-4363. doi: 10.1158/1078-0432.CCR-16-2876. Epub 2017 Mar 7. PubMed PMID: 28270495.

12: Zeng L, Beggs RR, Cooper TS, Weaver AN, Yang ES. Combining Chk1/2 Inhibition with Cetuximab and Radiation Enhances In Vitro and In Vivo Cytotoxicity in Head and Neck Squamous Cell Carcinoma. Mol Cancer Ther. 2017 Apr;16(4):591-600. doi: 10.1158/1535-7163.MCT-16-0352. Epub 2017 Jan 30. PubMed PMID: 28138028; PubMed Central PMCID: PMC5560482.

13: Ghelli Luserna Di Rorà A, Iacobucci I, Imbrogno E, Papayannidis C, Derenzini E, Ferrari A, Guadagnuolo V, Robustelli V, Parisi S, Sartor C, Abbenante MC, Paolini S, Martinelli G. Prexasertib, a Chk1/Chk2 inhibitor, increases the effectiveness of conventional therapy in B-/T- cell progenitor acute lymphoblastic leukemia. Oncotarget. 2016 Aug 16;7(33):53377-53391. doi: 10.18632/oncotarget.10535. PubMed PMID: 27438145; PubMed Central PMCID: PMC5288194.

14: Hong D, Infante J, Janku F, Jones S, Nguyen LM, Burris H, Naing A, Bauer TM, Piha-Paul S, Johnson FM, Kurzrock R, Golden L, Hynes S, Lin J, Lin AB, Bendell J. Phase I Study of LY2606368, a Checkpoint Kinase 1 Inhibitor, in Patients With Advanced Cancer. J Clin Oncol. 2016 May 20;34(15):1764-71. doi: 10.1200/JCO.2015.64.5788. Epub 2016 Apr 4. PubMed PMID: 27044938; PubMed Central PMCID: PMC5321045.

15: King C, Diaz HB, McNeely S, Barnard D, Dempsey J, Blosser W, Beckmann R, Barda D, Marshall MS. LY2606368 Causes Replication Catastrophe and Antitumor Effects through CHK1-Dependent Mechanisms. Mol Cancer Ther. 2015 Sep;14(9):2004-13. doi: 10.1158/1535-7163.MCT-14-1037. Epub 2015 Jul 3. PubMed PMID: 26141948.

Wu WH, Bonnet S, Shimauchi T, Toro V, Grobs Y, Romanet C, Bourgeois A, Vitry G, Omura J, Tremblay E, Nadeau V, Orcholski M, Breuils-Bonnet S, Martineau S, Ferraro P, Potus F, Paulin R, Provencher S, Boucherat O. Potential for inhibition of checkpoint kinases 1/2 in pulmonary fibrosis and secondary pulmonary hypertension. Thorax. 2021 Jul 5:thoraxjnl-2021-217377. doi: 10.1136/thoraxjnl-2021-217377. Epub ahead of print. PMID: 34226205.