MK-1775

MK-1775 - Names and Identifiers

Name	MK-1775
Synonyms	MK-1775 2-allyl-1-(6-(2-hydroxypropan-2-yl)pyridin-2-yl)-6-(4-(4-methylpiperazin-1-yl)phenylamino)-1H-pyrazolo[3,4-d]pyrimidin-3(2H)-one 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
CAS	955365-80-7

MK-1775 - Physico-chemical Properties

Molecular Formula	C27H32N8O2
Molar Mass	500.61
Density	1.292
Melting Point	179-181°C
Boling Point	723.8±70.0 °C(Predicted)
Appearance	Form solid, color Yellow
pKa	13.27±0.29(Predicted)
Storage Condition	-20°C
Stability	Stable for 2 years from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 3 months.
Use	Scientific research reagents are widely used in molecular biology, pharmacology and other scientific research, and are strictly prohibited from being used in human body. Adavosertib (AZD-1775; MK-1775) is an effective Wee1 inhibitor. This product can be used for scientific research experiments in related fields.

MK-1775 - Upstream Downstream Industry

Raw Materials

6-BROMOPYRIDINE-2-CARBOXYLIC ACID METHYL ESTER
2-allyl-1-(6-(2-hydroxypropan-2-yl)pyridin-2-yl)-6-(Methylthio)-1H-pyrazolo[3,4-d]pyriMidin-3(2H)-one
4-(4-Methylpiperazino)aniline
2-allyl-6-(Methylthio)-1H-pyrazolo[3,4-d]pyriMidin-3(2H)-one
2-(6-broMopyridin-2-yl)propan-2-ol

MK-1775 - Preparation solution concentration reference

	1mg	5mg	10mg
1 mM	1.998 ml	9.988 ml	19.976 ml
5 mM	0.4 ml	1.998 ml	3.995 ml
10 mM	0.2 ml	0.999 ml	1.998 ml
5 mM	0.04 ml	0.2 ml	0.4 ml

Last Update：2024-01-02 23:10:35

MK-1775 - Nature

Solubility

Soluble in DMSO (70 mg/ml)

Last Update：2024-04-10 22:29:15

MK-1775 - Uses and synthesis methods

product description

MK-1775 is an effective, highly selective Wee1 inhibitor. IC50 is 5.2 nM in cell-free test. Blocking G2 phase DNA damage checkpoint.

action

MK-1775 aims to cause some tumor cells to divide without normal DNA repair process, which eventually leads to cell death. Preclinical evidence shows that MK-1775 combined with DNA damage-inducing chemotherapy drugs can enhance anti-tumor properties compared with chemotherapy alone.

in vitro studies

MK-1775 inhibits Wee1 kinase in a ATP competitive manner. Compared with Wee1, MK-1775 has a 2-to 3-fold lower efficacy for Yes, an IC50 of 14 nM, a 10-fold lower efficacy for 7 other kinases, an inhibition rate of> 80% at a concentration of 1 μM, a more than 100-fold higher selectivity than human Myt 1, and an inhibition of cyclin-dependent kinase 1 (CDC2) phosphorylation at the selectable site (Thr14). By blocking Wee1 activity in WiDr cells loaded with mutant p53, DNA damage detection sites were abolished, MK-1775 treatment inhibited CDC2 basal phosphorylation at Tyr15 (CDC2Y15) site with EC50 of 49 nM and dose-dependent inhibition of gemcitabine-,carboplatin-or cisplatin-induced CDC2 phosphorylation and cell cycle arrest with EC50 of 82 nM and 81 nM,180 nM and 163 nM, and 159 nM and 160 nM, respectively. MK-1775 treatment with 30-100 nM alone had no significant antiproliferative effect in WiDr and H1299 cells, while the MK-1775 of 300 nM was sufficient to inhibit Wee1> 80%, showing mild but significant antiproliferative effect, with inhibition rates of 34.1% and 28.4% in WiDr and H1299 cells, respectively.

In vivo studies

MK-1775(~ 20 mg/kg) treatment alone showed minimal anti-tumor effect on WiDr xenografts, with T/C of 69% on the 3rd day in rats. In nude mouse HeLa-luc and TOV21G-shp53 xenograft models, MK-1775 antitumor efficacy alone is mild.

Last Update：2024-04-09 21:01:54