Danusertib, also known as PHA-739358, is a small-molecule 3-aminopyrazole derivative with potential antineoplastic activity. Aurora kinase inhibitor PHA-739358 binds to and inhibits the Aurora kinases, which may result in cell growth arrest and apoptosis in tumor cells in which Aurora kinases are overexpressed. This agent may preferentially bind to and inhibit Aurora B kinase. Aurora kinases, a family of serine-threonine kinases, are important regulators of cellular proliferation and division.

MedKoo Cat#: 200846 Name: Danusertib CAS#: 827318-97-8 Chemical Formula: C26H30N6O3 Exact Mass: 474.23794 Molecular Weight: 474.55 Elemental Analysis: C, 65.80; H, 6.37; N, 17.71; O, 10.11

Synonym: PHA739358; PHA-739358; PHA 739358; Danusertib.

IUPAC/Chemical Name: (R)-N-(5-(2-methoxy-2-phenylacetyl)-1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazol-3-yl)-4-(4-methylpiperazin-1-yl)benzamide

InChi Key: XKFTZKGMDDZMJI-HSZRJFAPSA-N

InChi Code: 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/h4-11,23H,12-17H2,1-2H3,(H2,27,28,29,33)/t23-/m1/s1

SMILES Code: O=C(NC1=NNC2=C1CN(C([C@H](OC)C3=CC=CC=C3)=O)C2)C4=CC=C(N5CCN(C)CC5)C=C4

Technical Data

Appearance: 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, not in water

Shelf Life: >5 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).

Harmonized System Code: 293490

Additional Information

PHA-739358 exhibits inhibitory activity against all known Aurora kinases as well as other cancer-relevant kinases such as the Bcr-Abl tyrosine kinase, including its multidrug-resistant T315I mutant. This mutation is responsible for up to 25% of all clinically observed resistances in CML patients undergoing Imatinib therapy. However, this particular mutation is predicted to play an even more important clinical role in the future, since in addition to Imatinib, it also confers resistance to second-generation Bcr-Abl inhibitors such as Nilotinib, Dasatinib, and Bosutinib. Therefore, combined Aurora and Bcr-Abl inhibition (the latter including high-grade resistance conferring mutations) with compounds such as Danusertib represents a promising new strategy for treatment of Bcr-Abl positive leukemias, especially those in second and third line of treatment. see http://www.ncbi.nlm.nih.gov/pubmed/20072840.      

References

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