SSK1

• CAT Number: I044697
• CAS Number: 2629250-69-5
• Molecular Formula: C31H34F2N4O18
• Molecular Weight: 788.61
• Purity: ≥95%
• Synonyms: [(2R,3S,4S,5R,6S)-3,4,5-triacetyloxy-6-[4-[[1-[(2R,4R,5R)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-2-oxopyrimidin-4-yl]carbamoyloxymethyl]-2-nitrophenoxy]oxan-2-yl]methyl acetate
• InChI: InChI=1S/C31H34F2N4O18/c1-13(39)48-12-21-23(50-14(2)40)24(51-15(3)41)25(52-16(4)42)27(54-21)53-19-6-5-17(9-18(19)37(46)47)11-49-30(45)35-22-7-8-36(29(44)34-22)28-31(32,33)26(43)20(10-38)55-28/h5-9,20-21,23-28,38,43H,10-12H2,1-4H3,(H,34,35,44,45)/t20-,21-,23+,24+,25-,26-,27-,28-/m1/s1
• InChIKey: DLQYTWCQXUJEML-XERWOCHESA-N
• SMILES: CC(=O)OCC1C(C(C(C(O1)OC2=C(C=C(C=C2)COC(=O)NC3=NC(=O)N(C=C3)C4C(C(C(O4)CO)O)(F)F)[N+](=O)[O-])OC(=O)C)OC(=O)C)OC(=O)C

SSK1, a senescence-specific killing compound, is a β-galactosidase-targeted proagent attenuates inflammation. SSK1 is activated by lysosomal β-galactosidase and selectively killed senescent cells through the activation of p38 MAPK and induction of apoptosis[1].
SSK1 (0.5 µM; 12-72 hours) activates the phosphorylation levels of both p38 MAPK and MKK3/MKK6 in senescent cells. SSK1 kills senescent cells through the activation of the p38 MAPK signaling pathway. SSK1 is able to induce mitochondrial DNA damage in senescent cells[1].
SSK1 (0.01-1 µM; 3 days) selectively and potently eliminates β-galactosidase-positive senescent cells within a wide therapeutic window[1].
SSK1 (0.5 mg/kg; i.p.; two days every week; for four weeks) could eliminate senescent cells and decrease senescence-associated markers in lung-injured mice[1].
In aged mice (20-month-old), SSK1 (0.5 mg/kg; 3 days every 2 weeks for 8 weeks) effectively clears senescent cells in different tissues, decreases the senescence- and age-associated gene signatures, attenuates low-grade local and systemic inflammation, and restores physical function[1].

Reference

[1]. Yusheng Cai, et al. Elimination of senescent cells by β-galactosidase-targeted prodrug attenuates inflammation and restores physical function in aged mice. Cell Res. 2020 Jul;30(7):574-589.
 [Content Brief]