GSK2807 TFA

InvivoChem Cat #:V4128CAS #:2245255-66-5Purity >=98%

Description: GSK2807 TFA, the trifluoroacetic acid salt form of GSK2807, is a novel, potent, selective and SAM-competitive inhibitor of SMYD3 with a Ki of 14 nM. SMYD3 is a lysine methyltransferase overexpressed in colorectal, breast, prostate, and hepatocellular tumors, and has been implicated as an oncogene in human malignancies. Methylation of MEKK2 by SMYD3 is important for regulation of the MEK/ERK pathway, suggesting the possibility of selectively targeting SMYD3 in RAS-driven cancers. Structural and kinetic characterization of SMYD3 was undertaken leading to a co-crystal structure of SMYD3 with a MEKK2-peptide substrate bound, and the observation that SMYD3 follows a partially processive mechanism. These insights allowed for the design of GSK2807, a potent and selective, SAM-competitive inhibitor of SMYD3 (Ki = 14 nM). A high-resolution crystal structure reveals that GSK2807 bridges the gap between the SAM-binding pocket and the substrate lysine tunnel of SMYD3. Taken together, the data demonstrate that small-molecule inhibitors of SMYD3 can be designed to prevent methylation of MEKK2 and these could have potential use as anticancer therapeutics.

Description:

References: Structure. 2016 May 3; 24(5):774-781.

References

Related CAS#: 2245255-65-4 (free base)

-20C for 3 years in powder form

Synonym: GSK2807 TFA; GSK2807 trifluoroacetic acid; GSK-2807 TFA; GSK-2807; GSK 2807
IUPAC/Chemical Name: (S)-2-amino-4-((((2R, 3S, 4R, 5R)-5-(6-amino-9H-purin-9-yl)-3, 4-dihydroxytetrahydrofuran-2-yl)methyl)(3-(dimethylamino)propyl)amino)butanoic acid compound with 2, 2, 2-trifluoroacetic acid (1:1)
InChi Key: FZPZIBBKUWOBTJ-CPQMNCBCSA-N
InChi Code: InChI=1S/C19H32N8O5.C2HF3O2/c1-25(2)5-3-6-26(7-4-11(20)19(30)31)8-12-14(28)15(29)18(32-12)27-10-24-13-16(21)22-9-23-17(13)27; 3-2(4, 5)1(6)7/h9-12, 14-15, 18, 28-29H, 3-8, 20H2, 1-2H3, (H, 30, 31)(H2, 21, 22, 23); (H, 6, 7)/t11-, 12+, 14+, 15+, 18+; /m0./s1
SMILES Code: O=C(O)[CH](N)CCN(C[CH]1O[CH](N2C=NC3=C(N)N=CN=C23)[CH](O)[CH]1O)CCCN(C)C.O=C(O)C(F)(F)F