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Products are for research use only. Not for human use. We do not sell to patients.
(PHA-739358; PHA739358; PHA 739358)
Danusertib Chemical Structure
|Product name: Danusertib|
|Cat. No.: HY-10179|
Danusertib (PHA-739358) is a pyrrolo-pyrazole and small molecule Aurora kinases inhibitor with IC50 of 13, 79, and 61 nM for Aurora A, B, and C, respectively.
IC50 Value: 13 nM(Aurora A); 79 nM(Aurora B); 61 nM(Aurora C)
Target: Aurora Kinase
in vitro: Danusertib inhibits the activities of other kinases such as FGFR1, Abl, Ret and Trka, with IC50 of 47 nM, 25 nM, 31 nM and 31 nM, respectively. In a cell assay, after treatment of wild-type and p53-deficient MEFs with Danusertib, the wild-type cells undergo an arrest in mitosis (4N) that is maintained for up to 48 h. The p53-deficient cells on the other hand do not arrest at the 4N DNA stage, but continues with additional rounds of DNA synthesis to become >8N. Treatment with Danusertib results in an increase in p53 protein levels and an associated increase in p21 protein, which is known to be transcriptionally regulated by p53.
in vivo: Danusertib significantly inhibits proliferation of K562 cells and virtually suppressed tumor growth during the 10-day treatment period. Administration of 25 mg/kg Danusertib (b.d. i.v.) to HL-60 xenograft rats results in 75% inhibition of tumor growth with complete regression in one animal. Danusertib results in biomarker modulation accompanied by inhibition of tumor growth. This is compatible with an expected mechanism of action of aurora kinase inhibition.
|M.Wt||474.55||Storage||Please store the product under the recommended conditions in the Certificate of Analysis.|
|Solvent & Solubility||
DMSO ≥90mg/mL Water <1.2mg/mL Ethanol ≥30mg/mL
|1 mg||5 mg||10 mg|
|1 mM||2.1073 mL||10.5363 mL||21.0726 mL|
|5 mM||0.4215 mL||2.1073 mL||4.2145 mL|
|10 mM||0.2107 mL||1.0536 mL||2.1073 mL|
|Product Name||Sponsor Only||Condition||Start Date||End Date||Phase||Last Change Date|
|Danusertib||Jonsson Comprehensive Cancer Center||Chronic myelocytic leukemia||31-MAR-07||Phase 2||03-NOV-10|
|Nerviano Medical Sciences Srl||Hormone refractory prostate cancer||30-SEP-07||30-APR-11||Phase 2||10-MAY-13|
|Nerviano Medical Sciences Srl||Multiple myeloma||31-OCT-08||30-SEP-10||Phase 2||08-OCT-09|
. Fancelli D, Moll J, Varasi M, et al. 1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazoles: identification of a potent Aurora kinase inhibitor with a favourable antitumor kinase inhibition profile. J Med Chem 2006; 49:7247-51.
. Gontarewicz A et al Simultaneous targeting of Aurora kinases and Bcr-Abl kinase by the small molecule inhibitor PHA-739358 is effective against imatinib-resistant BCR-ABL mutations including T315I Blood. 2008 Apr 15;111(8):4355-64.
. 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.Randomized phase II study of danusertib in patients with metastatic castration-resistant prostate cancer after docetaxel failure.BJU Int. 2012 Aug 29.
. Fraedrich K, Schrader J, Ittrich H, Keller G, Gontarewicz A, Matzat V, Kromminga A, Pace A, Moll J, Bl?ker M, Lohse AW, H?rsch D, Brümmendorf TH, Benten D.Targeting Aurora Kinases with Danusertib (PHA-739358) Inhibits Growth of Liver Metastases from Gastroenteropancreatic Neuroendocrine Tumors in an Orthotopic Xenograft Model.Clin Cancer Res. 2012 Sep 1;18(17):4621-32. Epub 2012 Jul 2.
. Fei F, Lim M, Schmidhuber S, Moll J, Groffen J, Heisterkamp N.Treatment of human pre-B acute lymphoblastic leukemia with the Aurora kinase inhibitor PHA-739358 (Danusertib).Mol Cancer. 2012 Jun 21;11(1):42.
Alisertib (MLN8237) is a selective Aurora A inhibitor with IC50 of 1.2 nM; has >200-fold higher selectivity for Aurora A than Aurora B.
AMG 900 is a potent and highly selective pan-Aurora kinases inhibitor for Aurora A/B/C with IC50 of 5 nM/4 nM /1 nM; >10-fold selective for Aurora kinases than p38(alpha), Tyk2, JNK2, Met and Tie2.
AT9283 is a small molecule a multi-targeted inhibitor with IC50s of 4, 1.2, 1.1 and approximate 3 nM for Bcr-Abl(T3151), JAK2 and JAK3, Aurora A and Aurora B, respectively.
Aurora A inhibitor I is a selective Aurora A inhibitor (Aurora A: IC50=0.0034 (mu)M; Aurora B IC50=3.4 (mu)M), (B/A ratio=1000).
AZD1152 (barasertib), pro-drug of barasertib-hQPA(HY-10126), is a selective Aurora B kinase inhibitor, AZD1152 inhibited the proliferation various types of human leukemia cells with an IC50 ranging from 3 nM to 40 nM.
AZD1152-HQPA is the active metabolite of AZD-1152, AZD1152-HQPA (Barasertib) is a highly selective Aurora B inhibitor with IC50 of 0.37 nM, ~100 fold more selective for Aurora B over Aurora A.
CCT 137690 is a potent inhibitor of Aurora kinases (IC50 values are 0.015, 0.019 and 0.025 (mu)M at Aurora A, Aurora C and Aurora B respectively).
CCT129202 is a Aurora kinase inhibitor with IC50 of 0.042 (plusmn) 0.022, 0.198 (plusmn) 0.05, and 0.227 (plusmn) 0.064 uM for Aurora A, Aurora B, and Aurora C, respectively.
CYC116 is a potent inhibitor of Aurora A/B with Ki of 8.0 nM/9.2 nM.
GSK1070916 is a reversible and ATP-competitive inhibitor of Aurora B/C with IC50 of 3.5 nM/6.5 nM; displays >100-fold selectivity against the closely related Aurora A-TPX2 complex(IC50=490 nM).