STAT5-IN-1 (STAT5 Inhibitor) is a cell-permeable inhibitor which suppresses Stat5 via binding to the SH2 domain.

AK-2292 is a potent and selective STAT5 PROTAC degrader, with a DC 50 of 0.10 μM. AK-2292 induces degradation of STAT5A/B proteins in vitro and in vivo. AK-2292 can induce tumor regression in acute myeloid leukemia and chronic myeloid leukemia xenograft mouse models [1] [2] .

PF15 TFA, a PROTAC targeting FLT3 kinase and CRBN, exhibits selective degradation of FLT3-ITD with a DC50 of 76.7 nM. The compound potently suppresses proliferation in FLT3-ITD-positive cells, reduces phosphorylation levels of FLT3 and STAT5, and demonstrates inhibition of tumor growth in murine leukemia models [1].

CAY10763 is a dual inhibitor of indolamine 2,3-dioxygenase 1 (IDO1; IC50= 46 nM) and STAT3 activation.1It binds to STAT3 (Kd= 530 nM) and selectively reduces the levels of STAT3 phosphorylated at the tyrosine in position 705 (STAT3Y705) over phosphorylated STAT3S727, STAT1, and STAT5 in SKOV3 cells when used at a concentration of 500 nM. It also inhibits STAT3 nuclear translocation in SKOV3 cells. CAY10763 is cytotoxic to HCT116, SKOV3, A549, and HepG2 cancer cells (IC50s = 37, 28, 33, and 12 nM, respectively). It reduces tumor growth in B16/F10 mouse melanoma and HepG2 mouse xenograft models when administered at doses of 100 and 10 mg/kg, respectively. 1.Huang, R., Jing, X., Huang, X., et al.Bifunctional naphthoquinone aromatic amide-oxime derivatives exert combined immunotherapeutic and antitumor effects through simultaneous targeting of indoleamine-2,3-dioxygenase and signal transducer and activator of transcription 3J. Med. Chem.63(4)1544-1563(2020)

Compound A8, known as JAK2-IN-9, is a selective JAK2 inhibitor with an IC50 of 5 nM. It effectively inhibits the phosphorylation of JAK2, STAT3, and STAT5, possesses metabolic stabilities, and induces apoptosis. This compound is utilized in the study of myeloproliferative neoplasms (MPNs) [1].

AC-4-130, a powerful inhibitor of the SH2 domain of STAT5, effectively hinders STAT5 activation, dimerization, nuclear translocation, and transcription of genes reliant on STAT5. This compound directly binds to STAT5, ultimately leading to cell cycle arrest and apoptosis in FLT3-ITD-driven leukemic cells. AC-4-130 exhibits notable anti-cancer properties and effectively suppresses abnormal STAT5 activity in acute myeloid leukemia (AML), making it a promising therapeutic option [1].

PF15, a selective FLT3-ITD degrader, serves as a PROTAC (proteolysis targeting chimera) tethering ligands for FLT3 kinase and CRBN. It exhibits a degradation concentration 50 (DC50) of 76.7 nM and notably impedes the proliferation of FLT3-ITD-positive cells. PF15 also reduces phosphorylation levels of FLT3 and STAT5 and demonstrates efficacy in inhibiting tumor growth in mouse models, suggesting potential applications in leukemia research [1].

JAK-IN-24, a JAK inhibitor, exhibits IC50 values of 0.534 nM and 24 nM in the presence of 4 μM and 1 mM ATP, respectively. Additionally, it effectively inhibits STAT5 phosphorylation induced by PBMC IL-15 with an IC50 of 86.171 nM.

BPR1J-340 is a potent and selective FLT3 inhibitor with potential anticancer activity. BPR1J-340 was identified as a novel potent FLT3 inhibitor by biochemical kinase activity (IC50 approximately 25 nM) and cellular proliferation (GC50 approximately 5 nM) assays. BPR1J-340 inhibited the phosphorylation of FLT3 and STAT5 and triggered apoptosis in FLT3-ITD(+) AML cells. The pharmacokinetic parameters of BPR1J-340 in rats were determined. BPR1J-340 also demonstrated pronounced tumor growth inhibition and regression in FLT3-ITD(+) AML murine xenograft models. The combination treatment of the HDAC inhibitor vorinostat (SAHA) with BPR1J-340 synergistically induced apoptosis via Mcl-1 down-regulation in MOLM-13 AML cells, indicating that the combination of selective FLT3 kinase inhibitors and HDAC inhibitors could exhibit clinical benefit in AML therapy.