Danusertib

• CAT Number: I004992
• CAS Number: 827318-97-8
• Molecular Formula: C₂₆H₃₀N₆O₃
• Molecular Weight: 474.55
• Purity: ≥95%
• Synonyms: N-[5-[(2R)-2-methoxy-2-phenylacetyl]-4,6-dihydro-1H-pyrrolo[3,4-c]pyrazol-3-yl]-4-(4-methylpiperazin-1-yl)benzamide
• Target: c-RET
• Solubility: DMSO: ≤ 7.5 mg/mL
• Storage: 3 years -20℃ powder
• IC50: 13 nM(Aurora A); 79 nM(Aurora B); 61 nM(Aurora C)
• InChI: InChI=1S/C26H30N6O3/c1-30-12-14-31(15-13-30)20-10-8-19(9-11-20)25(33)27-24-21-16-32(17-22(21)28-29-24)26(34)23(35-2)18-6-4-3-5-7-18/h3-11,23H,12-17H2,1-2H3,(H2,27,28,29,33)/t23-/m1/s1
• InChIKey: XKFTZKGMDDZMJI-HSZRJFAPSA-N
• SMILES: CN1CCN(CC1)C2=CC=C(C=C2)C(=O)NC3=NNC4=C3CN(C4)C(=O)C(C5=CC=CC=C5)OC

Danusertib（Cat No.:I004992）is a multi-targeted kinase inhibitor that primarily inhibits Aurora kinases A, B, and C, which are crucial regulators of mitosis. By blocking these kinases, Danusertib disrupts cell division, leading to mitotic arrest and apoptosis in rapidly dividing cancer cells. It also inhibits other kinases such as ABL and RET, broadening its therapeutic potential in oncology. Danusertib has been investigated in clinical trials for treating various cancers, including leukemia and solid tumors. Its ability to target multiple kinases makes it a promising agent in cancer treatment strategies.

Reference

1:Danusertib Induces Apoptosis, Cell Cycle Arrest, and Autophagy but Inhibits Epithelial to Mesenchymal Transition Involving PI3K/Akt/mTOR Signaling Pathway in Human Ovarian Cancer Cells. Zi D, Zhou ZW, Yang YJ, Huang L, Zhou ZL, He SM, He ZX, Zhou SF.Int J Mol Sci. 2015 Nov 13;16(11):27228-51. doi: 10.3390/ijms161126018. PMID: 26580601 Free PMC Article2:In situ electrochemical evaluation of dsDNA interaction with the anticancer drug danusertib nitrenium radical product using the DNA-electrochemical biosensor. Diculescu VC, Oliveira-Brett AM.Bioelectrochemistry. 2016 Feb;107:50-7. doi: 10.1016/j.bioelechem.2015.10.004. Epub 2015 Oct 24. PMID: 26523506 3:A phase I study of danusertib (PHA-739358) in adult patients with accelerated or blastic phase chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia resistant or intolerant to imatinib and/or other second generation c-ABL therapy. Borthakur G, Dombret H, Schafhausen P, Brummendorf TH, Boissel N, Jabbour E, Mariani M, Capolongo L, Carpinelli P, Davite C, Kantarjian H, Cortes JE.Haematologica. 2015 Jul;100(7):898-904. doi: 10.3324/haematol.2014.115279. Epub 2015 Apr 17. PMID: 25887498 Free PMC Article4:Danusertib, a potent pan-Aurora kinase and ABL kinase inhibitor, induces cell cycle arrest and programmed cell death and inhibits epithelial to mesenchymal transition involving the PI3K/Akt/mTOR-mediated signaling pathway in human gastric cancer AGS and NCI-N78 cells. Yuan CX, Zhou ZW, Yang YX, He ZX, Zhang X, Wang D, Yang T, Pan SY, Chen XW, Zhou SF.Drug Des Devel Ther. 2015 Mar 2;9:1293-318. doi: 10.2147/DDDT.S74964. eCollection 2015. PMID: 25767376 Free PMC Article5:The pan-inhibitor of Aurora kinases danusertib induces apoptosis and autophagy and suppresses epithelial-to-mesenchymal transition in human breast cancer cells. Li JP, Yang YX, Liu QL, Zhou ZW, Pan ST, He ZX, Zhang X, Yang T, Pan SY, Duan W, He SM, Chen XW, Qiu JX, Zhou SF.Drug Des Devel Ther. 2015 Feb 17;9:1027-62. doi: 10.2147/DDDT.S74412. eCollection 2015. PMID: 25733818 Free PMC Article6:Efficacy and safety of biweekly i.v. administrations of the Aurora kinase inhibitor danusertib hydrochloride in independent cohorts of patients with advanced or metastatic breast, ovarian, colorectal, pancreatic, small-cell and non-small-cell lung cancer: a multi-tumour, multi-institutional phase II study. Schöffski P, Besse B, Gauler T, de Jonge MJ, Scambia G, Santoro A, Davite C, Jannuzzo MG, Petroccione A, Delord JP.Ann Oncol. 2015 Mar;26(3):598-607. doi: 10.1093/annonc/mdu566. Epub 2014 Dec 8. PMID: 25488684 7:Electrochemical evaluation of Abelson tyrosine-protein kinase 1 activity and inhibition by imatinib mesylate and danusertib. Diculescu VC, Enache TA.Anal Chim Acta. 2014 Oct 3;845:23-9. doi: 10.1016/j.aca.2014.06.025. Epub 2014 Jun 17. PMID: 25201268 8:Randomized phase II study of danusertib in patients with metastatic castration-resistant prostate cancer after docetaxel failure. Meulenbeld HJ, Bleuse JP, Vinci EM, Raymond E, Vitali G, Santoro A, Dogliotti L, Berardi R, Cappuzzo F, Tagawa ST, Sternberg CN, Jannuzzo MG, Mariani M, Petroccione A, de Wit R.BJU Int. 2013 Jan;111(1):44-52. doi: 10.1111/j.1464-410X.2012.11404.x. Epub 2012 Aug 29. PMID: 22928785 Free Article9:The human Aurora kinase inhibitor danusertib is a lead compound for anti-trypanosomal drug discovery via target repurposing. Ochiana SO, Pandarinath V, Wang Z, Kapoor R, Ondrechen MJ, Ruben L, Pollastri MP.Eur J Med Chem. 2013 Apr;62:777-84. doi: 10.1016/j.ejmech.2012.07.038. Epub 2012 Jul 31. PMID: 22889561 Free PMC Article10:Targeting aurora kinases with danusertib (PHA-739358) inhibits growth of liver metastases from gastroenteropancreatic neuroendocrine tumors in an orthotopic xenograft model. Fraedrich K, Schrader J, Ittrich H, Keller G, Gontarewicz A, Matzat V, Kromminga A, Pace A, Moll J, Bläker M, Lohse AW, Hörsch D, Brümmendorf TH, Benten D.Clin Cancer Res. 2012 Sep 1;18(17):4621-32. doi: 10.1158/1078-0432.CCR-11-2968. Epub 2012 Jul 2. PMID: 22753592 Free Article