MK-1775 Chemical Properties

Melting point:

179-181°C

Boiling point:

723.8±70.0 °C(Predicted)

Density 

1.292

storage temp. 

-20°C

solubility 

Soluble in DMSO (70 mg/ml)

pka

13.27±0.29(Predicted)

form 

solid

color 

Yellow

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.

MK-1775 Usage And Synthesis

Description

MK-1775 is a small molecule inhibitor of the tyrosine kinase WEE1 with potential antineoplastic sensitizing activity. MK-1775 selectively targets and inhibits WEE1, a tyrosine kinase that phosphorylates cyclin-dependent kinase 1 (CDK1, CDC2) to inactivate the CDC2/cyclin B complex. Inhibition of WEE1 activity prevents the phosphorylation of CDC2 and impairs the G2 DNA damage checkpoint. This may lead to apoptosis upon treatment with DNA damaging chemotherapeutic agents. MK-1775 is a type of biological therapy. It is a cancer growth blocker. It stops signals that cancer cells use to divide and grow. MK-1775 has been used in trials studying the treatment of LYMPHOMA, Neoplasms, Ovarian Cancer, Tongue Carcinoma, and Adult Glioblastoma, among others.

Uses

MK 1775 is used in biological studies for the abrogation of G2/M checkpoint through WEE1 inhibition in combination with chemotherapy as a promising therapeutic approach for mesothelioma.

Definition

ChEBI: 1-[6-(2-hydroxypropan-2-yl)-2-pyridinyl]-6-[4-(4-methyl-1-piperazinyl)anilino]-2-prop-2-enyl-3-pyrazolo[3,4-d]pyrimidinone is a member of piperazines.

in vitro

mk-1775 dose-dependently inhibited phosphorylation of cdc2 at tyr15 and abrogated the g2dna damage checkpoint. mk-1775 inhibited wee1 kinase in an atp-competitive manner with an ic50 value of 5.2 nmol/l in the in vitro kinase assays. compared to wee1, mk-1775 displayed 2- to 3-fold less potency against yes with the ic50value 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 inhibited 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 inhibited the basal phosphorylation of cdc2 at tyr15 (cdc2y15) with an ec50 of 49 nm, and dose-dependently suppressed gemcitabine-, carboplatin- or cisplatin-induced phosphorylation of cdc2 and cell cycle arrest, with the ec50 of 82 nm and 81 nm, 180 nm and 163 nm, as well as 159 nm and 160 nm, respectively. in widr and h1299 cells, mk-1775 treatment (30-100 nm)showed no significant antiproliferative effects, whereas mk-1775 at 300 nm was sufficient to inhibit wee1 by >80%, displayed moderate but significant antiproliferative effects by 34.1% in widr cells and 28.4% in h1299 cells [1].

target

Wee1

storage

Store at -20°C

References

Hirai et al. (2009) Small-molecule inhibition of Wee1 kinase by MK-1775 selectively sensitizes p53-deficient tumor cells to DNA-damaging agents; Cancer Ther.?8 2992 Pan et al. (2021) A novel WEE1 pathway for replication stress responses; Plants 7 209 Guo et al. (2022) WEE1 inhibition induces anti-tumor immunity by activating ERV and the dsRNA pathway; Exp. Med. 219 e20210789 Seo et al. (2021) Inhibition of WEE1 Potentiates Sensitivity to PARP Inhibitor in Biliary Tract Cancer; Cancer Res. Treat. Epub ahead of print

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