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Products
Pharmacology
Type
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- Technical support
- Resources
Tat-braftide
Cat. No. KS-220
Structure:
H-Gly-Arg-Lys-Lys-Arg-Arg-Gln-Arg-Arg-Arg-Pro-Gln-PEG-Thr-Arg-His-Val-Asn-Ile-Leu-Leu-Phe-Met-OH
Other Names:
GRKKRRQRRRPQ-PEG-TRHVNILLFM
Activity:
Allosteric BRAF inhibitor
Tat-braftide is a BRAF kinase inhibitor consisting of the10-mer peptide inhibitor, braftide, TRHVNILLFM, linked by PEG to the cell penetrating sequence TAT. Tat-braftide was designed to bind to the dimer interface of the BRAF kinase domain, and accordingly it inhibits BRAF kinase activity by disrupting BRAF dimers, with an IC50 of 43 nM in kinase assays. Additionally, targeting the dimer interface of BRAF kinase leads to protein degradation of both RAF and MEK, uncovering a novel scaffolding function of RAF in protecting large MAPK complexes from protein degradation. Tat-braftide shows efficient inhibition and degradation of WT BRAF and BRAFG469A in a variety of cells exhibiting either RAS dependence or independence. Tat−braftide treatment causes dose dependent inhibition of growth of HCT116 and HCT-15 cells, with EC50 values of 7.1 and 6.6 μM, demonstrating potent inhibiton of cell viability in KRAS-mutated colon cancer cells.
Gunderwala et al (2019) Development of Allosteric BRAF Peptide Inhibitors Targeting the Dimer Interface of BRAF. ACS Chem Biol. 14(7) 1471 PMID: 31243962
Cope et al (2020) Analyses of the oncogenic BRAFD594G variant reveal a kinase-independent function of BRAF in activating MAPK signaling. J Biol Chem. 295(8) 2407 PMID: 31929109
Related areas
All cell penetrating peptides >
All kinase modulators >
All cancer research categories >
Technical Data
| Structure | H-Gly-Arg-Lys-Lys-Arg-Arg-Gln-Arg-Arg-Arg-Pro-Gln-PEG-Thr-Arg-His-Val-Asn-Ile-Leu-Leu-Phe-Met-OH |
| Molecular Weight | 2990.47 |
| Formula | C128H227N51O30S |
| Sequence | GRKKRRQRRRPQXTRHVNILLFM |
| Modifications | X = PEG = -NH-CH2-CH2-O-CH2-CH2-O-CH2-C=O- |
Solubility and Storage
| Solubility | Soluble in water |
| Appearance | Freeze dried solid |
| Storage | Store dry, frozen and in the dark |
Batch Specific Data
| Purity | >95% by hplc |
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Recent citations
A new publication from the University of Ljubljana uses MCA-AVLQSGFR-Lys(Dnp)-Lys-NH2, the FRET substrate for the severe acute respiratory syndrome coronavirus main protease (SARS-CoV Mpro), to determine the inhibitory potential of plant polyphenols
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