MK-1775 (Synonyms: MK1775,MK 1775) |
Catalog No.GC16030
One-Click Copy Product Info
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MK-1775 is a potent and selective small-molecule inhibitor of Wee1 kinase with an IC50 value of 5.2 nM.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 955365-80-7
Sample solution is provided at 25 µL, 10mM.
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MK-1775 is a potent and selective small-molecule inhibitor of Wee1 kinase with an IC50 value of 5.2nM. The IC50 of MK-1775 for inhibiting Yes is 14nM[1].
In vitro efficacy test it shown that MK-1775 inhibited phosphorylation of CDC2 at Tyr15 with an EC50 value of 85nM in cells pretreated with gemcitabine. MK-1775 treatment induced pHH3 in a dose-dependent manner with an EC50 value of 81nM[1]. In vitro efficacy test it indicated that treatment with 10nM panobinostat in combination with 250nM or 500nM MK-1775 in U937 cells, the combination index (CI) values were 0.95 and 0.73, while U937 cells treated with 20nM panobinostat in combination with 250nM or 500nM MK-1775 were 0.39 and 0.40, respectively[2]. In vitro, treatment with 0.1, 0.3, 1μM of MK-1775 for 48h in LSCC cells and TU212 and KB-3-1 cells dose-dependently induced early apoptosis (Annexin V+/PI-) and late apoptosis (Annexin V+/PI+) . Moreover, after MK-1775 treatment, the protein levels of apoptosis marker cleaved-PARP was increased in a dose-depend manner[4].
In vivo, daily oral administration of MK-1775 (60mg/kg) for 5 days enhanced the response of H1299 xenografts in nude mice to radiotherapy[3]. In vivo, Nude Mice were treated with 50mg/kg orally MK-1775 for 14 days, MK-1775 inhibited the growth of KB-3-1 xenografts with the inhibition ratio of 30.04% by reducing the tumor volumes and weights, but MK-1775 can cause toxicity in mice azt the indicated dose[4]. Treatment with either MK-1775 (20mg/kg) or panobinostat (10mg/kg) alone in mice bearing BxPC-3 xenograft tumors had modest delay of externally measurable tumor growth (30.9% and 37.8% on day 20, respectively). Combination the MK-1775 (20mg/kg) with panobinostat (10mg/kg) can marked delay the tumor growth with 58.7% tumor growth inhibition on day 20[5].
References:
[1]Hirai H, et al. MK-1775, a small molecule Wee1 inhibitor, enhances anti-tumor efficacy of various DNA-damaging agents, including 5-fluorouracil. Cancer Biol Ther. 2010 Apr 1;9(7):514-22.
[2]Qi W, et al. Synergistic anti-leukemic interactions between panobinostat and MK-1775 in acute myeloid leukemia ex vivo. Cancer Biol Ther. 2015;16(12):1784-93.
[3]Bridges KA, et al. MK-1775, a novel Wee1 kinase inhibitor, radiosensitizes p53-defective human tumor cells. Clin Cancer Res. 2011 Sep 1;17(17):5638-48.
[4]Yuan ML, et al. Inhibition of WEE1 Suppresses the Tumor Growth in Laryngeal Squamous Cell Carcinoma. Front Pharmacol. 2018 Sep 28;9:1041.
[5]Wang G, et al. Synergistic antitumor interactions between MK-1775 and panobinostat in preclinical models of pancreatic cancer. Cancer Lett. 2015 Jan 28;356(2 Pt B):656-68.
| Cell experiment [1]: | |
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Cell lines |
H1299 cells |
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Preparation Method |
H1299 cells were treated for 1h with 200nM MK-1775, irradiated with 7.5Gy, incubated for an additional 18h in MK-1775, and harvested for assessment of apoptosis at 24, 48, and 72h post-irradiation. |
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Reaction Conditions |
200nM; 24, 48, and 72h |
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Applications |
The dose of 7.5Gy induced levels of apoptosis of only about 5% above control at any time point and these levels of apoptosis were not significantly enhanced by MK-1775. |
| Animal experiment [2]: | |
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Animal models |
6-week-old female nu/nu athymic mice |
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Preparation Method |
When tumors reached a volume of ~200mm3, mice were individually identified and randomly assigned to treatment groups, with 5–6 mice (8–10 evaluable tumors) in each group: 1) control; 2) MK-1775 (30mg/kg. p.o., once daily for 4 weeks; 3) GEM (100mg/kg, i.p., twice weekly on days 1 and 4) for 4 weeks; 4) GEM followed 24h later by MK-1775 in the above mentioned dose. |
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Dosage form |
30mg/kg; p.o.; once daily for 4 weeks |
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Applications |
Single agent MK-1775 treatment produced greater than 50% inhibition of tumor growth in two xenografts (PANC286 and PANC198). |
References: | |
| Cas No. | 955365-80-7 | SDF | |
| Synonyms | MK1775,MK 1775 | ||
| Chemical Name | 1-[6-(2-hydroxypropan-2-yl)pyridin-2-yl]-6-[4-(4-methylpiperazin-1-yl)anilino]-2-prop-2-enylpyrazolo[3,4-d]pyrimidin-3-one | ||
| Canonical SMILES | CC(C)(C1=NC(=CC=C1)N2C3=NC(=NC=C3C(=O)N2CC=C)NC4=CC=C(C=C4)N5CCN(CC5)C)O | ||
| Formula | C27H32N8O2 | M.Wt | 500.6 |
| Solubility | ≥ 25.03mg/mL in DMSO | Storage | Store at -20°C |
| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.9976 mL | 9.988 mL | 19.976 mL |
| 5 mM | 399.5 μL | 1.9976 mL | 3.9952 mL |
| 10 mM | 199.8 μL | 998.8 μL | 1.9976 mL |
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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
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Quality Control & SDS
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- Purity: >99.50% Appearance: A solid
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Average Rating: 5 (Based on Reviews and 10 reference(s) in Google Scholar.)