Uses
BDA-366 is a potent Bcl2 antagonist (Ki = 3.3 nM), binding Bcl2-BH4 domain with high affinity and selectivity. BDA-366 induces conformational change in Bcl2 that abrogates its antiapoptotic function, converting it from a survival molecule to a cell death inducer. BDA-366 suppresses growth of lung cancer cells[1].
Definition
ChEBI: BDA-366 is a member of the class of anthraquinone that is 1,4-diamino-9,10-anthraquinone in which the two amino groups are carrying 3-(diethylamino)-2-hydroxypropyl and (oxiran-2-yl)methyl substituents. It exhibits anti-cancer properties. It has a role as an antineoplastic agent and an apoptosis inducer. It is an anthraquinone, an epoxide, a tertiary amino compound, a secondary amino compound and a secondary alcohol. It is functionally related to a 9,10-anthraquinone.
Biological Activity
bda-366 is a selective antagonist of bcl2 bh4 domain with ki value of 3.3 nm [1].bcl2 is an important anti-apoptotic protein. bcl2 homology 4 (bh4) domain is required for its antiapoptotic function, thus acts as a promising anticancer target [1].bda-366 is a selective bcl2 inhibitor. bda-366 induced conformational change of bcl2 that exposed the bh3 domain, resulting in abrogation of its prosurvival function and conversion of bcl2 to a prodeath protein. in non-small cell lung cancer (nsclc) and small cell lung cancer (sclc) cells, bda-366 selectively bound to bcl2 with high affinity. bda-366 induced apoptosis by bcl2-dependent bax activation and cytochrome c release. in h460 cells, bda-366 reduced bcl2/ip3r binding, which then increased ca2+ release [1].in mice bearing h460 lung cancer xenografts, treatment with bda-366 (0, 10, 20, and 30 mg/kg/day) via i.p. route for 14 days induced apoptosis and potently inhibited tumor growth in a dose-dependent way. there was no significant toxicity at the maximum therapeutic dose. in tumor tissue from patients with nsclc, bda-366 synergized with rad001 and resulted in significantly greater inhibition of lung cancer growth compared with either agent alone [1].
References
[1]. han b, park d, li r, et al. small-molecule bcl2 bh4 antagonist for lung cancer therapy. cancer cell, 2015, 27(6): 852-863.
