Merck, 5335140001, GADD45b/MKK7 Inhibitor, DTP3

General description
A cell permeable, bioavailable D-tripeptide that specifically binds to MKK7 in 1:1 stoichiometry and disrupts the GADD45b/MKK7 complex in an allosteric mechanism (Kd = 65 nM, IC₅₀ = 160 pM). Does not affect the activity of 142 other protein kinases. Exhibits potent and selective activity in both multiple myeloma (MM) and non-MM cell lines expressing high levels of GADD45b, however, it is completely inactive in tumor cells featuring low GADDb expression. Displays potency similar to bortezomib, but has about 100-fold greater selectivity for cancer cells, and unlike bortezomib, it does not display any toxic effects in normal cell lines. Shown to activate JNK, but does not affect p38, ERK, or IKK/NF-κB signaling in sensitive GADD45b dependent MM cell lines. Abolishes the growth of myeloma xenografts in mice (14.5 mg/kg/day) and retains anticancer activity in an orthotopic xenograft model of MM. Displays desirable pharmacokinetic profile (t1/2 = 1.26 h and AUC = 6.43 mg/h/ml; at ~10 mg/kg, i.v).

Please note that the molecular weight for this compound is batch-specific due to variable water content. Please refer to the vial label or the certificate of analysis for the batch-specific molecular weight. The molecular weight provided represents the baseline molecular weight without water.
Biochem/physiol Actions
Cell permeable: yes
Primary Target
GADD45b/MKK7
Reversible: yes
Packaging
Packaged under inert gas
Physical form
Supplied as a HCl salt.
Preparation Note
Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.
Other Notes
Ac-YRF-NH2
Tomatore, L., et al. 2014. Cancer Cell.26, 495.
Legal Information
CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany
Disclaimer
Toxicity: Standard Handling (A)