MK-1775 (AZD1775), WEE1 Inhibitor

MK-1775 (AZD1775) is a highly potent, selective and orally bioavailable Wee1 kinase inhibitor with IC50 of 5.2 nM. It abrogated DNA damaged checkpoints induced by gemcitabine, carboplatin, and cisplatin etc. and enhanced the anti-tumor efficacy of these agents selectively in p53-deficient tumor cells. At tolerated doses, MK-1775 treatment leads to xenograft tumor growth inhibition or regression. It inhibits Wee1 in H3K36me3-deficient cells results in RRM2 reduction, critical dNTP depletion, S-phase arrest, and apoptosis. MK-1775 can regresse H3K36me3-deficient tumor xenografts too. Right now MK-1775 is in phase I/II clinical trials for various cancers.

Product information

CAS Number: 955365-80-7

Molecular Weight: 500.60

Formula: C27H32N8O2

Synonym:

AZD1775

adavosertib

Chemical Name: 2-allyl-1-(6-(2-hydroxypropan-2-yl)pyridin-2-yl)-6-((4-(4-methylpiperazin-1-yl)phenyl)amino)-1,2-dihydro-3H-pyrazolo[3,4-d]pyrimidin-3-one

Smiles: CN1CCN(CC1)C1C=CC(=CC=1)NC1=NC2=C(C=N1)C(=O)N(CC=C)N2C1=CC=CC(=N1)C(C)(C)O

InChiKey: BKWJAKQVGHWELA-UHFFFAOYSA-N

InChi: InChI=1S/C27H32N8O2/c1-5-13-34-25(36)21-18-28-26(29-19-9-11-20(12-10-19)33-16-14-32(4)15-17-33)31-24(21)35(34)23-8-6-7-22(30-23)27(2,3)37/h5-12,18,37H,1,13-17H2,2-4H3,(H,28,29,31)

Technical Data

Appearance: Solid Power.

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO up to 100 mM

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥360 days if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

MK-1775 was used at 1 µM in vitro and cellular assays.

In Vivo:

MK-1775 was orally dosed to mice at 20 mg/Kg once per day.

References:

1. Hirai H, et al. Small-molecule inhibition of Wee1 kinase by MK-1775 selectively sensitizes p53-deficient tumor cells to DNA-damaging agents. (2009) Mol Cancer Ther. 8(11):2992-3000.
2. Rajeshkumar NV, et al. MK-1775, a potent Wee1 inhibitor, synergizes with gemcitabine to achieve tumor regressions, selectively in p53-deficient pancreatic cancer xenografts. (2011) Clin Cancer Res. 17(9):2799-806.
3. Guertin AD, et al. Preclinical evaluation of the WEE1 inhibitor MK-1775 as single-agent anticancer therapy. (2013) Mol Cancer Ther. 12(8):1442-52.
4. Pfister SX, et al. Inhibiting WEE1 Selectively Kills Histone H3K36me3-Deficient Cancers by dNTP Starvation. (2015) Cancer Cell. 28(5):557-68.

Products are for research use only. Not for human use.