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K67

Cat. No. M8733
K67 Structure
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Biological Activity

K67 is a specific inhibitor against the interaction between KEAP1 (Kelch-like ECH-associated protein 1) DC (double glycine repeat and C-terminal region) domain and S349-phosphorylated (human Ser349, mouse Ser351) KIR (Keap1-interacting region) of p62/SQSTM1, thereby preventing phospho-p62 from blocking KEAP1-DC and NRF2 (nuclear factor erythroid 2-related factor 2) DLGex motif association. K67 effectively inhibits the proliferation of HCC (hepatocellular carcinoma) cultures (by 59% of Huh7 cells post 72 h 50 μM K67 treatment) with high cellular p62 S351-phosphorylation by restoring KEAP1-driven NRF2 ubiquitination and degradation.

Chemical Information
Molecular Weight 582.69
Formula C29H30N2O7S2
CAS Number 2046250-48-8
Solubility (25°C) DMSO: 10 mg/mL
Storage Powder          -20°C   3 years ;  4°C   2 years
In solvent       -80°C   6 months ;  -20°C   1 month
Conversion of different model animals based on BSA (PMID: 27057123)
Species Mouse Rat Rabbit Guinea pig Hamster Dog
Weight (kg) 0.02 0.15 1.8 0.4 0.08 10
Body Surface Area (m2) 0.007 0.025 0.15 0.05 0.02 0.5
Km factor 3 6 12 8 5 20
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.

References

[1] Zhiyuan Zhang, et al. HERC3 regulates epithelial-mesenchymal transition by directly ubiquitination degradation EIF5A2 and inhibits metastasis of colorectal cancer

[2] Daisuke Yasuda, et al. Inhibitors of the protein-protein interaction between phosphorylated p62 and Keap1 attenuate chemoresistance in a human hepatocellular carcinoma cell line

[3] I Fried, et al. Merkel cell carcinoma

[4] Alison M Urvalek, et al. Regulation of the oncoprotein KLF8 by a switch between acetylation and sumoylation

[5] R Mushin. The occurrence of enteropathogenic Escherichia coli 0128: K67 (B12)

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