SD-36

SD-36 is a potent and efficacious STAT3 PROTAC degrader ( K d =~50 nM), and demonstrates high selectivity over other STAT members. SD-36 also effectively degrades mutated STAT3 proteins in cells and suppresses the transcriptional activity of STAT3 ( IC 50 =10 nM). SD-36 exerts robust anti-tumor activity, and achieves complete and long-lasting tumor regression in mouse tumor models. SD-36 is composed of the STAT3 inhibitor SI-109, a linker, and an analog of Cereblon ligand Lenalidomide for E3 ubiquitin ligase In Vitro SD-36 inhibits the growth of a subset of acute myeloid leukemia and anaplastic large-cell lymphoma cell lines by inducing cell-cycle arrest and/or apoptosis. SD-36 (0.005-5 μM; 4 days) demonstrates potent activity (IC 50 ＜2 μM) in MOLM-16, DEL, Karpas-299, KI-JK, SU-DHL-I, SUP-M2 cell lines. SD-36 (1 μM; 5 hours) completely depletes both monomeric and dimeric STAT3 protein in MOLM-16 cells. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Cell Viability AssayCell Line: MOLM-16, DEL, Karpas-299, KI-JK, SU-DHL-I, SUP-M2 cell lines Concentration: 0.005, 0.05, 0.5, 5 μM Incubation Time: 4 days Result: Demonstrated potent activity (IC 50 ＜2 μM) in those cell lines. Western Blot AnalysisCell Line: MOLM-16 cells Concentration: 1 μM Incubation Time: 5 hours Result: Completely depletes both monomeric and dimeric STAT3 protein. In Vivo SD-36 (25-100 mg/kg; i.v.; weekly dosing for 4 weeks) achieves complete and long-lasting tumor regression in mice . SD-36 effectively inhibits tumor growth at 25 and 50 mg/kg administered on day 1, 3, and 5 per week and achieved complete tumor regression at 100 mg/kg with the same schedule in the SU-DHL-1 xenograft model . SD-36 at 50 mg/kg 3 times per week completely inhibits tumor growth in the SUP-M2 tumor model . MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: SCID female mice (MOLM-16 xenograft model) Dosage: 25, 50, 100 mg/kg Administration: i.v.; weekly dosing for 4 weeks Result: At 25 and 50 mg/kg weekly dosing for 4 weeks effectively inhibited tumor growth. At either 100 mg/kg weekly or 50 mg/kg twice weekly for 4 weeks induced complete tumor regression. Form:Solid IC50& Target:STAT3 50 nM (Kd) Cereblon

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