MK-1775 (Synonyms: MK1775,MK 1775) |
| Catalog No.GC16030 |
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 5.2 nM. MK-1775 is 2- to 3-fold less potent against Yes with an IC50 of 14 nM.[1].
In vitro efficacy test it shown that MK-1775 inhibited phosphorylation of CDC2 at Tyr15 with an EC50 value of 85 nM in cells pretreated with gemcitabine. MK-1775 treatment induced pHH3 in a dose-dependent manner with an EC50 value of 81 nM.[1] In vitro efficacy test it indicated that treatment with 10 nM panobinostat in combination with 250 nM or 500 nM MK-1775 in U937 cells, the combination index (CI) values were 0.95 and 0.73, while U937 cells treated with 20 nM panobinostat in combination with 250 nM or 500 nM MK-1775 were 0.39 and 0.40, respectively.[3] In vitro, treatment with 0.1, 0.3, 1 μM of MK-1775 for 48 h 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[5].
In vivo, treatment with 60 mg/kg MK-1775 orally enhances H1299 xenograft tumor response to fractionated radiotherapy in nude mice.[2] In vivo experiment it indicated that treatment with either MK-1775 (20 mg/kg) or panobinostat (10 mg/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). However, combination the MK-1775 (20 mg/kg) with panobinostat (10 mg/kg) can marked delay the tumor growth with 58.7% tumor growth inhibition on day 20.[4] In vivo, Nude Mice were treated with 50 mg/kg orally MK-1775, MK-1775 inhibited the growth of KB-3-1 xenografts with the inhibition ratio of 30.04% by reducing the tumor volumes and weights. And MK-1775 also can cause toxicity in mice at the indicated dose.[6].
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]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.
[3]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.
[4]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.
[5]Yuan ML, et al Inhibition of WEE1 Suppresses the Tumor Growth in Laryngeal Squamous Cell Carcinoma. Front Pharmacol. 2018 Sep 28;9:1041.
[6]Yuan ML, et al. Inhibition of WEE1 Suppresses the Tumor Growth in Laryngeal Squamous Cell Carcinoma. Front Pharmacol. 2018 Sep 28;9:1041.
| Cell experiment [1]: | |
Cell lines | H1299 cells |
Preparation Method | H1299 cells were treated for 1 h with 200 nM MK-1775, irradiated with 7.5 Gy, incubated for an additional 18 h in MK-1775, and harvested for assessment of apoptosis at 24, 48, and 72 h post-irradiation. |
Reaction Conditions | 200 nM, 1 h |
Applications | The dose of 7.5 Gy 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]: | |
Animal models | 6-week-old female nu/nu athymic mice |
Preparation Method | When tumors reached a volume of ~200 mm3, 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 (30 mg/kg. p.o., once daily for 4 weeks; 3) GEM (100 mg/kg, i.p., twice weekly on days 1 and 4) for 4 weeks; 4) GEM followed 24 h later by MK-1775 in the above mentioned dose. |
Dosage form | 30 mg/kg. p.o., |
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 |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| 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 | 0.3995 mL | 1.9976 mL | 3.9952 mL |
| 10 mM | 0.1998 mL | 0.9988 mL | 1.9976 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
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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 ddH2O, 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.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
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- Purity: >99.50%
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Average Rating: 5 (Based on Reviews and 10 reference(s) in Google Scholar.)
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