RGNCY-0102 (SLLN-15 Autophagy inducer)

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SLLN-15 is a potent autophagy enhancer that selectively activated cytostatic macroautophagy/autophagy in TNBC preclinical models.  SLLN-15 induced a dose-dependent anti-proliferative activity in TNBC cell lines MDA-MB-231 and BT-20 by inducing autophagy and autophagic flux.  This was associated with a selective inhibition of AKT-MTOR signalling.  In contrast, a known autophagy inducer and MTOR inhibitor, rapamycin, did not replicate SLLN-15's effect on TNBC cells.  SSLN-15-induced inhibition of cancer cell proliferation was also shown to be autophagy-dependent as siRNA-mediated targeting of autophagy regulators (BECNI, ATG and ATG7) significantly protected against SLLN-15-induced inhibition of cancer cell proliferation.  In SLLN-15-induced autophagy in TNBC cells was associated with decreased AUKRA expression, decreased AKT phosphorylation and subsequent blockage of AKT-MTOR pathway.  Oral SLLN-15 was also shown to have potent anticancer and anti-metastatic activity in vivo in mice bearing TNBC.

Systematic Name:  (S)-N2-(4-selenomorpholinophenyl)-N6-(tetrahydroselenophen-3-yl)-9H-purine-2,6-diamine

SMILES:  [C@H]1(C[Se]CC1)NC2=NC(NC3=CC=C(N4CC[Se]CC4)C=C3)=NC5=C2N=CN5

Formula:  C19H23N7Se2

Mol Wt:  507.36

PMID:  30773992