SKU: H032  / 
    CAS Number: 102042-09-1

    21-Hydroxyoligomycin A

    $277.35 - $970.71

    21-Hydroxyoligomycin A is a rare member of the Oligomycin class, isolated as a co-metabolite of nemadectin, hence it was originally named Nemadectin omega. Only limited literature references are available. In-house testing suggests that 21-Hydroxyoligomycin has a more selective action against mammalian tumor cell lines than Oligomycin A, exhibiting only weak antifungal and nematocidal activity.  21-Hydroxyoligomycin A can Inhibit K-Ras plasma membrane localization and is therefore a putative anti-cancer agent.

    21-Hydroxyoligomycin A is soluble in ethanol, methanol, DMF and DMSO but practically insoluble in water. 

    Additional Oligomycin products can be found here.

    Mechanism of Action

    21-Hydroxyoligomycin A can inhibit K-Ras plasma membrane localization are therefore putative cancer chemotherapeutic agents.  The study of its inhibitory mechanism of action are expected to reveal pathways and molecular targets to control K-Ras (Salim et al, 2016).

    Single-crystal X-ray analysis established the structure and absolute configuration of 21-Hydroxyoligomycin A (Wagenaar et al, 2017).

    Cancer Applications It is reported to be cytotoxic to human colon cancer SW620 cells (IC50 = 14.4 μM), andvcolorectal carcinoma cells (IC50 > 3 uM), to inhibit the ABC transporter efflux pump P-glycoprotein (P-gp).

    Ras proteins are membrane-bound GTPases that regulate cell growth, proliferation and differentiation. Mutant forms of Ras are prominent in many human cancers. Oncogenic mutant K-Ras must be localized to the plasma membrane to be functional. 21-Hydroxyoligomycin A prevented K-Ras plasma membrane localization (IC50 = 4.82 nM). Oligomycins A-E were also able to inhibit K-Ras plasma membrane localization with (IC50 range of ~ 1.5-14 nM (Wagenaar et al, 2007). 

    Inhibitors of K-Ras plasma membrane localization are therefore putative cancer chemotherapeutic agents. The study of K-Ras inhibitory mechanism of action are expected to reveal pathways and molecular targets to control K-Ras. This could inform the development of new probes to better interrogate K-Ras-dependent cancers.
    Solubility Soluble in ethanol, methanol, DMF and DMSO but practically insoluble in water.
    Source Streptomyces cyaneogriseus ssp. noncyanogenus (LL-F28249)
    References

    Salim AA et al (2016)  Oligomycins as inhibitors of K-Ras plasma membrane localisation. Org. Biomol. Chem. 14(2):711-715  PMID 26565618

    Thomas DI, Cove JH, Baumberg S, Jones CA and Rudd BA (1991)  Plasmid effects on secondary metabolite production by a streptomycete synthesizing an anthelmintic macrolide. J Gen Microbiol. 137:2331-2337  PMID 1770350

    Wagenaar MM, Williamson RT, Ho DM, and Carter GT (2007)  Structure and absolute stereochemistry of 21-Hydroxyoligomycin A.. J Nat Prod. 70(3):367-371  PMID 17249728