Prexasertib free base
Prexasertib, also know LY2606368, is a n inhibitor of checkpoint kinase 1 (chk1) with potential antineoplastic activity. Upon administration, LY2606368 selectively binds to chk1, thereby preventing activity of chk1 and abrogating the repair of damaged DNA. This may lead to an accumulation of damaged DNA and may promote genomic instability and apoptosis. LY2606368 may potentiate the cytotoxicity of DNA-damaging agents and reverse tumor cell resistance to chemotherapeutic agents.
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Chemical Information
| Name | Prexasertib free base |
|---|---|
| Iupac Chemical Name | 5-((5-(2-(3-aminopropoxy)-6-methoxyphenyl)-1H-pyrazol-3-yl)amino)pyrazine-2-carbonitrile |
| Synonyms | LY2606368; LY 2606368; LY-2606368; Prexasertib free base |
| Molecular Formula | C18H19N7O2 |
| Molecular Weight | 365.39 |
| Smile | N#CC1=NC=C(NC2=NNC(C3=C(OC)C=CC=C3OCCCN)=C2)N=C1 |
| InChiKey | DOTGPNHGTYJDEP-UHFFFAOYSA-N |
| InChi | InChI=1S/C18H19N7O2/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/h2,4-5,8,10-11H,3,6-7,19H2,1H3,(H2,22,23,24,25) |
| CAS Number | 1234015-52-1 |
| Related CAS |
Ordering Information
| Packaging | Price | Availability | Purity | Shipping Time |
|---|---|---|---|---|
| Bulk | Enquiry | Enquiry | Enquiry |
| Formulation | Solid powder |
|---|---|
| Purity | 98% Min. |
| Storage | 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 |
| Handling | |
| 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. |
| HS Code |
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| Mechanism | |
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| Clinical study |
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.
Chemical Structure
