Compound class:
Synthetic organic
Comment: S1g-2 is a small molecule that binds to heat shock protein 70 (Hsp70) and disrupts its regulatory interaction with the pro-apoptotic protein BCL2 like 11 (a.k.a. Bim; BCL2L11) [2]. S1g-2 is used as an experimental tool to demonstrate the potential antitumour effect of inhibiting the Hsp70/Bim interaction in therapy resistant cancers [2-4]. The ligand binds within Hsp70's nucleotide-binding domain (NBD) [2] at a site that is distinct from that of the allosteric anticancer compound MKT-077 (PubChem CID 6912334) [1].
|
|
References |
1. Rousaki A, Miyata Y, Jinwal UK, Dickey CA, Gestwicki JE, Zuiderweg ER. (2011)
Allosteric drugs: the interaction of antitumor compound MKT-077 with human Hsp70 chaperones. J Mol Biol, 411 (3): 614-32. [PMID:21708173] |
2. Song T, Guo Y, Xue Z, Guo Z, Wang Z, Lin D, Zhang H, Pan H, Zhang X, Yin F et al.. (2021)
Small-molecule inhibitor targeting the Hsp70-Bim protein-protein interaction in CML cells overcomes BCR-ABL-independent TKI resistance. Leukemia, 35 (10): 2862-2874. [PMID:34007045] |
3. Song T, Yin F, Wang Z, Zhang H, Liu P, Guo Y, Tang Y, Zhang Z. (2023)
Hsp70-Bim interaction facilitates mitophagy by recruiting parkin and TOMM20 into a complex. Cell Mol Biol Lett, 28 (1): 46. [PMID:37237369] |
4. Yin F, Song T, Wang Z, Liu J, Zhang H, Tang Y, Zhang Z. (2024)
Hsp70-Bim incoherent feedforward loop contributes to cell-fate heterogeneity and fractional killing. Br J Pharmacol, 181 (5): 659-669. [PMID:37706555] |