SD-36

Research use only, not for human use.

SD-36 is a selective and efficient STAT3 protein degrader (Kd=~50 nM) with antitumor activity that promotes growth inhibition and induces apoptosis by inhibiting Mcl-1 in gliomas.SD-36 inhibits the transcriptional activity of STAT3.

SD-36 is a potent and efficacious STAT3 PROTAC degrader (Kd=~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 (IC50=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. SD-36 is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.

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 (IC50＜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.Cell Viability Assay Cell 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 (IC50＜2 μM) in those cell lines.Western Blot Analysis Cell Line:MOLM-16 cells Concentration:1 μM Incubation Time:5 hours Result:Completely depletes both monomeric and dimeric STAT3 protein.

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. 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.

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Apoptosis

Apoptosis

Apoptosis | STAT

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2429877-44-9

1158.15

C59H62F2N9O12P

>98% (HPLC)

In Vitro:?DMSO : 50 mg/mL (43.17 mM; Ultrasonic )

C(N[C@H](C(NC(C1=CC=CC=C1)C2=CC=CC=C2)=O)CCC(N)=O)(=O)[C@H]3N4[C@](CC3)(CCN(C(CCCCCC#CC5=C6C(C(=O)N(C6)C7C(=O)NC(=O)CC7)=CC=C5)=O)C[C@H](NC(=O)C8=CC=9C(N8)=CC=C(C(P(=O)(O)O)(F)F)C9)C4=O)[H]

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(-20℃)

With Ice Pack

≥ 2 years