Manumycin A

Manumycin A is an antibiotic that act as a potent and selective farnesyltransferase inhibitor [1]．

Farnesyltransferase posttranslationally-modifies proteins by adding a farnesyl group to the -SH of the cysteine near the end of target proteins to form a thioether linkage. Farnesylation makes become membrane-associated.

Manumycin A is a potent and selective ras farnesyltransferase inhibitor. In cultured MB cells, Manumycin A (≥10 ?M) blocked p21 ras farnesylation and induced apoptosis [1]. In rat VSMCs, Manumycin A signi?cantly consistently inhibited [3H]-thymidine incorporation in a dose-dependent way and inhibited cell growth. In a trans-well assay, manumycin A (50 ng/ml) inhibited VSMC migration in the presence of 10 ng/ml of PDGF [2].

In myotonic dystrophy type 1 (DM1) mice with 250 CUG repeats, Manumycin A significantly reduced Clcn1 exon 7A inclusion and corrected aberrant splicing of Clcn1 [3].

References:
Wang W, Macaulay RJ.  Apoptosis of medulloblastoma cells in vitro follows inhibition of farnesylation using manumycin A. Int J Cancer. 1999 Jul 30;82(3):430-4.
Kouchi H, Nakamura K, Fushimi K, et al.  Manumycin A, inhibitor of ras farnesyltransferase, inhibits proliferation and migration of rat vascular smooth muscle cells. Biochem Biophys Res Commun. 1999 Nov 2;264(3):915-20.
Oana K, Oma Y, Suo S, et al.  Manumycin A corrects aberrant splicing of Clcn1 in myotonic dystrophy type 1 (DM1) mice. Sci Rep. 2013;3:2142.