MK-1775

Description

Biological Activity

Protocol(Only for Reference)

Clinical Trial Information( data from http://clinicaltrials.gov)

Chemical Information

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Customer Reviews (2)

Kinase Assay:

^[1]

Cell Assay:

^[1]

Animal Study:

^[1]

References

貨號 Cat. No.: S1525
規格 Size: 5~200mg
品牌 Brand: Selleckchem

MK-1775

Catalog No.S1525

2 Reviews 4 Product Citations

MK-1775 is a potent and selective Wee1 inhibitor with IC50 of 5.2 nM; hinders G2 DNA damage checkpoint. Phase 2.

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10mM/1mLIn DMSO	USD 299	In stock	0 1 2 3 4 5 6 7 8 9 10
5mg	USD 214	In stock	0 1 2 3 4 5 6 7 8 9 10
10mg	USD 340	In stock	0 1 2 3 4 5 6 7 8 9 10
25mg	USD 592	In stock	0 1 2 3 4 5 6 7 8 9 10
50mg	USD 970	In stock	0 1 2 3 4 5 6 7 8 9 10

Distributor Tel: +886-2-2827-1197jimmy@new.abscience.com.tw

In vitro kinase assays	Recombinant human Wee1 is used. Kinase reaction is conducted with 10 μM ATP, 1.0 μCi of [γ-³³P]ATP, and 2.5 μg of poly(Lys, Tyr) as a substrate in the presence of increasing concentrations of MK-1775 at 30°C for 30 minutes. Radioactivity incorporated into the substrate is trapped on MultiScreen-PH plates and is counted on a liquid scintillation counter.

Cell lines	WiDr, NCI-H1299, TOV21G, and HeLa
Concentrations	Dissolved in DMSO, final concentrations ~10 μM
Incubation Time	24 hours
Method	Cells are treated with or without gemcitabine for 24 hours, then with MK-1775 for an additional 24 hours. Cell viability is determined with a WST-8 kit using SpectraMax. Cellular caspase-3/7 activities are determined with a Caspase-3/7 Glo kit.

Animal Models	Immunodeficient nude rats (F344/NJcl-rnu) bearing WiDr, HeLa-luc, or TOV21G-shp53 tumors
Dosages	~20 mg/kg/day
Administration	Orally
Solubility	0.5% methylcellulose, 30 mg/mL

NCT Number	Recruitment	Conditions	Sponsor /Collaborators	Start Date	Phases
NCT01164995	Recruiting	Epithelial Ovarian Cancer	The Netherlands Cancer Institute\|Merck	2010-07	Phase 2
NCT01357161	Recruiting	Ovarian Cancer	Merck	2011-07	Phase 2
NCT01748825	Recruiting	Neoplasms\|Lymphoma	National Institutes of Health Clinical Center (CC)\|National Cancer Institute (NCI)	2012-11	Phase 1
NCT01827384	Not yet recruiting	Neoplasms	National Institutes of Health Clinical Center (CC)\|National Cancer Institute (NCI)	2013-03	Phase 2
NCT01849146	Not yet recruiting	Adult Giant Cell Glioblastoma\|Adult Glioblastoma\|Adult Gliosarcoma\|Recurrent Adult Brain Tumor	National Cancer Institute (NCI)	2013-04	Phase 1

Download MK-1775 SDF

Molecular Weight (MW)	500.6
Formula	C₂₇H₃₂N₈O₂
CAS No.	955365-80-7

Storage	3 years -20â„ƒPowder
Storage	6 months-80â„ƒin DMSO
Syonnyms	N/A

Solubility (25°C) *	In vitro	DMSO	80 mg/mL (159 mM)
		Water	0.0001 mg/mL (<1 mM)
		Ethanol	<1 mg/mL (<1 mM)
	In vivo	0.5% methylcellulose,	30 mg/mL
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Name	2-allyl-1-(6-(2-hydroxypropan-2-yl)pyridin-2-yl)-6-(4-(4-methylpiperazin-1-yl)phenylamino)-1,2-dihydropyrazolo[3,4-d]pyrimidin-3-one

Stock Solution (1ml DMSO)	1mM	10mM	20mM	30mM
Mass(mg)	0.5006	5.006	10.012	15.018

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Description

MK-1775 is a potent and selective Wee1 inhibitor with IC50 of 5.2 nM; hinders G2 DNA damage checkpoint. Phase 2.

5.2 nM ^[1]

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. ^[1]

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. ^[1]

The first reported Wee1 inhibitor.

Click to enlarge	Rating
	Source	MK-1775 purchased from Selleck
	Method	Fow cytometry/Western blotting
	Cell Lines	U2OS cells
	Concentrations	300/1000 nM
	Incubation Time	1 h
	Results	Inhibition of WEE1 kinase by MK-1775 led to increased uptake of the nucleoside analog EdU during the 30 to 90 min after MK-1775 addition (Fig. A). MK-1775 also led to decreased tyrosine 15 inhibitory phosphorylation on CDK1 and increased phosphorylation of CDK substrates. We found that inhibition of WEE1 markedly reduced the replication fork rates (Fig. C). depletion of CDT1 could normalize fork speed in response to WEE1 inhibition by MK-1775.