product name BDA-366
Description: BDA-366 is a potent and selective small-molecule Bcl2-BH4 domain antagonist and binds BH4 with high affinity and selectivity. 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.
References: Oncotarget. 2016 May 10;7(19):27753-63; Cancer Cell. 2015 Jun 8;27(6):852-63.
423.5
Formula
C24H29N3O4
CAS No.
1909226-00-1
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 84 mg/mL (198.3 mM)
Water: <1 mg/mL
Ethanol: 5 mg/mL (11.8 mM)
Solubility (In vivo)
Synonyms
other peoduct :
| In Vitro |
In vitro activity: BDA-366 induces robust apoptosis in MM(Multiple myeloma) cell lines and primary MM cells by inducing BCL2 conformational change. BDA-366 induces a conformational change in the BCL2 molecule that converts it to a death protein, and inhibits lung cancer growth in vitro and in vivo. BDA-366 did not bind to other Bcl2 family members, including Bcl-XL, Mcl-1, or Bfl-1/A1, indicating the specificity of its Bcl2 binding. BDA-366 induces apoptotic cell death in a Bax-dependent manner and induces calcium (Ca2+) release via inhibition of Bcl2/IP3R interaction. Kinase Assay: Cell Assay: Human MM cell lines RPMI8226 and U266 were treated with BDA366 at increasing concentrations (0, 0.1, 0.25, 0.5μM) for 48hr. Cells were harvested, stained with Annexin V and propidium iodide (PI), and subjected to FACS analysis. Apoptotic cells were gated on the Annexin V positive population. Annexin V+PI− cells were early apoptotic cells, Annexin+PI+ cells were late apoptotic cells, and Annexin−PI+ cells were necrotic cells. |
|---|---|
| In Vivo | Delivery of BDA-366 substantially suppressed the growth of human MM xenografts in NOD-scid/IL2Rγ null mice, without significant cytotoxic effects on normal hematopoietic cells or body weight. Also, BDA-366 suppresses lung cancer growth via induction of apoptosis in animal models. The BH4 antagonist BDA-366 exhibits potent efficacy against human lung cancer in vivo without platelet reduction. |
| Animal model | NSG mice |
| Formulation & Dosage | Dissolved in DMSO, diluted in PBS; 10 mg/kg; i.p. |
| References | Oncotarget. 2016 May 10;7(19):27753-63; Cancer Cell. 2015 Jun 8;27(6):852-63. |
