Biological Activity
SW076956 is an early BCL-2/Beclin 1 interaction inhibitor used in autophagy-modulation research. SW076956 reduced Beclin-1/Bcl-2 co-immunoprecipitation while sparing Bax/Bcl-2 and Bim/Bcl-2 interactions in the reported assays.
In Vitro
| Endpoint | Model / conditions / source | Reported result |
|---|---|---|
| Cellular interaction | HeLa cells expressing Myc-Bcl-2; 12 h compound treatment. [2], Fig. 4 | SW076956 reduced Beclin-1/Bcl-2 co-immunoprecipitation while sparing Bax/Bcl-2 and Bim/Bcl-2 interactions in the reported assays. |
| Autophagic flux | HeLa GFP-LC3 cells; SW076956 20 µM for 24 h, with or without bafilomycin A1. [2], Fig. 5 | Increased GFP-LC3 puncta and LC3-II; further increases with bafilomycin supported increased flux rather than blocked maturation. |
| Pathway dependence | Beclin-1 knockdown experiments. [2] | Loss of Beclin-1 prevented the compound-associated increase in autophagosome number. |
In Vivo
No compound-specific animal efficacy result is established by the sources summarized here.
Compound and Evidence Context
| Endpoint | Model / conditions / source | Reported result |
|---|---|---|
| Parent versus optimized analogues | Subsequent Bcl-2/Beclin-1 inhibitor study. [1] | Nanomolar activity and NMR binding data reported for optimized compound 35 are not assigned to SW076956. |
Interpretation
Do not substitute optimized-analogue potency or selectivity values for the parent SW076956 compound.
Original studies
References
- Dong X, et al. Novel Bcl-2 Inhibitors Selectively Disrupt the Autophagy-Specific Bcl-2-Beclin 1 Protein-Protein Interaction. ACS medicinal chemistry letters (2022).
- Chiang WC, et al. High Throughput Screens to Identify Autophagy Inducers that Function by Disrupting Beclin 1/Bcl-2 Binding. ACS Chemical Biology (2018).