Home >> Chk1 and MK2 Inhibitors set
Related Products
Chk1 and MK2 Inhibitors set Chk1- and MK2 inhibitors

Catalog No.A9908
Size Price Stock Qty
In stock

Tel: +1-832-696-8203

Email: [email protected]

Worldwide Distributors


Sample solution is provided at 25 µL, 10mM.


Long Term Storage: -20°C
Kit/Set Contains: Contains the following inhibitors:
Cat.No.Product NameSizePuritySolubility
B1437PF-47773610mg98.00%Soluble in DMSO > 10 mM
B5549PF-364402210mg98.00%Soluble in DMSO > 10 mM


PF477736 and PF3644022 are potent and selective Chk1- and MK2 inhibitors, respectively.The simultaneous Chk1- and MK2 inhibition with PF477736 and PF3644022 is proposed as a therapeutic strategy for the treatment of KRAS-or BRAF-driven cancers. [1]

Chk1 and MK2 are both critical components of the G2/M checkpoint, which are essential for avoiding mitotic entry of cells suffering from genotoxic damage [2].Chk1 and Chk2 are important effector kinases in the canonical DNA damage response (DDR) network through the upstreamkinases ATR and ATM[3] (Jackson and Bartek, 2009).The p38/MK2 pathway is a widespread stress-kinase pathway that operates in parallel to Chk1. Chk1 and MK2 control checkpoint initiation and maintenance, respectively [4]. The activity of both kinases converges on mediating inhibitory phosphorylations onCDC25 familymembers to induce a subsequent cell-cycle arrest by blocking CDC25B-dependent CDK activation [2].

KRAS is one of the most frequently mutated onco-genes in human cancer. Acute expression of oncogenic KRAS induces genotoxic damage. Oncogenic KRAS mutations are associated with addiction to Chk1-/MK2-mediated checkpoints. [1]

Strong synergistic effects in cell-cycle checkpoint had been shown between PF477736 and PF3644022 in 33 out of the 96 cell lines, specifically in KRAS- and BRAF-driven cells. KRAS-mutant cancer displays intrinsic genotoxic stress, leading to tonic Chk1- and MK2 activity. Co-treatment of PF477736 and PF3644022leads to mitotic catastrophe in KRAS-mutant cells. [1]

In xenograft mice models, including distinct Kras-or Braf-driven autochthonous murine cancer models, this actionable synergistic interaction is validated. In KRAS-or BRAF-mutant tumorcells directly isolated from patients, the combined checkpoint inhibition induces apoptotic cell death. [1]

1.Dietlein F, Kalb B2, Jokic M et al.A Synergistic Interaction between Chk1- and MK2 Inhibitors in KRAS-Mutant Cancer.Cell. 2015 Jul 2;162(1):146-59.
2.Reinhardt, H.C., and Yaffe, M.B. (2013). Phospho-Ser/Thr-binding domains: navigating the cell cycle and DNA damage response. Nat. Rev. Mol. Cell Biol. 14, 563–580.
3.Jackson, S.P., and Bartek, J. The DNA-damage response in humanbiology and disease. Nature. 2009. 461, 1071–1078.
4.Reinhardt, H.C., Hasskamp, P., Schmedding, I., et al. DNA damage activates a spatially distinct late cytoplasmic cell-cycle checkpoint network controlled by MK2-mediated RNA stabilization. 2010. Mol. Cell 40, 34–49.