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Products are for research use only. Not for human use. We do not sell to patients.
(AZD-1775; AZD1775; AZD 1775)
MK-1775 Chemical Structure
|Product name: MK-1775|
|Cat. No.: HY-10993|
MK-1775 is a potent and selective Wee1 inhibitor with IC50 of 5.2 nM; hinders G2 DNA damage checkpoint.
IC50 Value: 5.2 nM
in vitro: MK-1775 inhibits Wee1 kinase in an ATP-competitive manner. Compared to Wee1, MK-1775 displays 2- to 3-fold less potency against Yes with IC50 of 14 nM, 10-fold less potency against seven other kinases with >80% inhibition at 1 μM, and >100-fold selectivity over human Myt 1, another kinase that inhibits cyclin-dependent kinase 1 (CDC2) by phosphorylation at an alternative site (Thr14). By abrogating the DNA damage checkpoint via blockade of Wee1 activity in WiDr cells bearing mutated p53, MK-1775 treatment inhibits the basal phosphorylation of CDC2 at Tyr15 (CDC2Y15) with EC50 of 49 nM, and suppresses gemcitabine-, carboplatin- or cisplatin-induced phosphorylation of CDC2 and cell cycle arrest in a dose-dependent manner, with EC50 of 82 nM and 81 nM, 180 nM and 163 nM, as well as 159 nM and 160 nM, respectively. MK-1775 treatment alone at 30-100 nM has no significant antiproliferative effect in WiDr and H1299 cells, whereas MK-1775 at 300 nM, sufficient to inhibit Wee1 by >80%, displays moderate but significant antiproliferative effects by 34.1% in WiDr cells and 28.4% in H1299 cells.
in vivo: MK-1775 treatment alone at ~20 mg/kg displays minimal antitumor effects against WiDr xenografts in rats with T/C of 69% at day 3. Antitumor efficacy by MK-1775 alone in the nude rat HeLa-luc and TOV21G-shp53 xenograft models models is also moderate.
|M.Wt||500.6||Storage||Please store the product under the recommended conditions in the Certificate of Analysis.|
|Solvent & Solubility||
10 mM in DMSO
|1 mg||5 mg||10 mg|
|1 mM||1.9976 mL||9.9880 mL||19.9760 mL|
|5 mM||0.3995 mL||1.9976 mL||3.9952 mL|
|10 mM||0.1998 mL||0.9988 mL||1.9976 mL|
|Product Name||Sponsor Only||Condition||Start Date||End Date||Phase||Last Change Date|
|MK-1775||The University Health Network||Metastatic head and neck cancer||30-SEP-13||31-MAR-16||Phase 2||12-SEP-13|
|Merck & Co Inc||Ovary tumor||31-JUL-11||28-FEB-15||Phase 2||17-OCT-13|
|Merck & Co Inc||Uterine cervix tumor||31-MAY-10||30-JUN-11||Phase 2||27-JUN-11|
|The University Health Network||Squamous cell carcinoma||30-SEP-13||31-MAR-16||Phase 2||12-SEP-13|
|National Cancer Institute||Advanced solid tumor||31-MAR-13||31-MAR-17||Phase 2||29-OCT-13|
|Netherlands Cancer Institute||Ovary tumor||31-JUL-10||30-SEP-13||Phase 2||13-SEP-12|
. Bridges KA, Hirai H, Buser CA, Brooks C, Liu H, Buchholz TA, Molkentine JM, Mason KA, Meyn RE.MK-1775, a novel Wee1 kinase inhibitor, radiosensitizes p53-defective human tumor cells.Clin Cancer Res. 2011 Sep 1;17(17):5638-48. Epub 2011 Jul 28.
. Rajeshkumar NV, De Oliveira E, Ottenhof N, Watters J, Brooks D, Demuth T, Shumway SD, Mizuarai S, Hirai H, Maitra A, Hidalgo M.MK-1775, a potent Wee1 inhibitor, synergizes with gemcitabine to achieve tumor regressions, selectively in p53-deficient pancreatic cancer xenografts.Clin Cancer Res. 2011 May 1;17(9):2799-806. Epub 2011 Mar 9.
. Sarcar B, Kahali S, Prabhu AH, Shumway SD, Xu Y, Demuth T, Chinnaiyan P.Targeting radiation-induced G(2) checkpoint activation with the Wee-1 inhibitor MK-1775 in glioblastoma cell lines.Mol Cancer Ther. 2011 Dec;10(12):2405-14. Epub 2011 Oct 12.
. Kreahling JM, Gemmer JY, Reed D, Letson D, Bui M, Altiok S.MK1775, a selective Wee1 inhibitor, shows single-agent antitumor activity against sarcoma cells.Mol Cancer Ther. 2012 Jan;11(1):174-82. Epub 2011 Nov 14.
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