Onalespib

Description

Onalespib is a selective inhibitor of Hsp90 (IC₅₀ = 18 nM). It induces the degradation of specific Hsp90 client proteins, including mutant EGFR, for up to seven days in tumor cell lines in vitro and up to three days in vivo. Onalespib is retained in tumor xenografts and is efficacious in a range of xenograft models.

What are the applications of Application

AT13387 is a selective, potent Hsp90 (heat shock protein 90) inhibitor

Definition

ChEBI: Onalespib is a member of the class of isoindoles that is isoindole in which the amino group has been acylated by a 2,4-dihydroxy-5-isopropylbenzoyl group and in which position 5 of the isoidole moiety has been substituted by a (4-methylpiperazin-1-yl)methyl group. A second-generation Hsp90 inhibitor. It has a role as a Hsp90 inhibitor and an antineoplastic agent. It is a member of resorcinols, a member of benzamides, a tertiary carboxamide, a member of isoindoles and a N-alkylpiperazine.

Mode of action

Onalespib selectively binds to Hsp90, thereby inhibiting its chaperone function and promoting the degradation of oncogenic signaling proteins involved in tumor cell proliferation and survival. Hsp90, a chaperone protein upregulated in a variety of tumor cells, regulates the folding, stability and degradation of many oncogenic signaling proteins and has been used as a biomarker of HSP90 inhibition.

References

Efficacy of Onalespib, a Long-Acting Second-Generation HSP90 Inhibitor, as a Single Agent and in Combination with Temozolomide against Malignant Gliomas
https://pubchem.ncbi.nlm.nih.gov/compound/Onalespib