SD-436 is a highly selective and efficient STAT3 PROTAC degrader, with a DC50 of 0.5 μM. It exhibits IC50 values of 19 nM for STAT3, 270 nM for STAT1, 360 nM for STAT4, and >10 μM for both STAT5 and STAT6. SD-436 promotes the ubiquitination and degradation of STAT3, and it induces tumor regression. This compound is applicable for tumor research, including studies on leukemia and lymphoma.

STAT6:>10 μM, STAT3:19 nM, STAT5:>10 μM, STAT1:270 nM

SD-436 inhibits the growth of the MOLM-16 leukemia cell line and the SU-DHL-1 and SUP-M2 lymphoma cell lines, with IC50 values of 0.038 μM, 0.43 μM, and 0.39 μM, respectively. At concentrations ranging from 0.1 nM to 40 μM over 20 hours, SD-436 reduces the levels of STAT3 protein in human PBMCs, SU-DHL-1, and MOLM-16 cell lines. It also significantly decreases levels of mutant STAT3 (STAT3 K658R) protein in the Pfeiffer cell line in a dose-dependent manner, with a DC50 of 2.5 nM. SD-436 exhibits excellent stability in the plasma of mice, rats, dogs, monkeys, and humans, with a T1/2 greater than 120 minutes. Additionally, SD-436 shows minimal inhibitory effects on the human ether-a-go-go-related gene potassium channel, with hERG inhibition rates of 1.3% at 3 μM and 1.1% at 30 μM.

Administering SD-436 (5 mg/kg, intravenous injection, single dose) effectively induces rapid, complete, and lasting suppression of STAT3 in mouse normal tissues (liver and spleen) and in MOLM-16 xenograft tumor tissues. In leukemic and lymphomatous mouse xenograft models, SD-436 (5-25 mg/kg, intravenous) demonstrates antitumor activity.