TrkB Inhibitor

GZ-389988 is a potent pan-TRK inhibitor with IC₅₀ values ​​of 0.3, 0.1, and 0.5 nM for TRKA, TRKB, and TRKC, respectively. GZ-389988 can be used to study NTRK fusion-positive tumors.

Licorisoflavan A (7-O-Methyllicorisoflavan B) is a isoflavan-quinone, that can be isolated from Glycyrrhiza uralensis. Licorisoflavan A exhibits anti-inflammatory and antimicrobial properties. It can inhibit the secretion of IL-6 and chemokines by LPS-stimulated macrophages in a concentration-dependent manner, and also suppress the secretion of MMP-7, MMP-8, and MMP-9 in macrophages. Licorisoflavan A exertes potent antidepressant-like effects involving BDNF-TrkB pathway and AMPA receptors.

Cyclotraxin B TFA is a BBB-penetrable and selective TrkB inhibitor. Cyclotraxin B TFA inhibits BDNF-induced TrkB activity in a non-competitive manner, with an IC₅₀ of 0.30 nM. Cyclotraxin B TFA has analgesic and anxiolytic effects.

PF-07245303 is a ITK/TRK inhibitor. PF-07245303 reduces the production of inflammatory cytokines such as IL-4 and IFNγ, and inhibits the phosphorylation of PLCγ1. PF-07245303 inhibits nerve growth factor-induced basophil activation and the phosphorylation of TRKA. PF-07245303 reduces oxazolone-induced ear swelling in mouse ear tissues. PF-07245303 is applicable to research related to atopic dermatitis.

YTB53 is a MNK1 and MNK2 inhibitor with IC₅₀s of 37 nM and 9 nM, respectively. YTB53 inhibits PDGFRα, TRKB and FLT3 in leukemia cells. YTB53 induces cell cycle arrest, apoptosis, pyroptosis, and mitochondrial dysfunction. YTB53 exhibits antiangiogenic effects. YTB53 can be used for the study of acute myeloid leukemia (AML).

TRK II-IN-1 is a potent type II TRK inhibitor, with IC₅₀s of 3.3, 6.4, 4.3 and 9.4 nM, for TRKA/B/C and TRKA^G667C, respectively. TRK II-IN-1 also inhibits FLT3, RET, and VEGFR2 with IC₅₀s of 1.3, 9.9, and 71.1 nM, respectively. TRK II-IN-1 can be used for the research of TRK driven cancers.

JND4135 is a Type II TRK inhibitor with IC₅₀ values of 2.79, 3.19, and 3.01 nM against TRKA, TRKB, TRKC, respectively. JND4135 can overcome resistance from TRK xDFG and other mutant forms in the BaF3 stable model, inhibiting phosphorylation of both WT and xDFG mutant TRKs, along with their downstream signaling molecules. JND4135 can induce G0/G1 phase arrest and apoptosis in BaF3–CD74-TRKA-G667C cells. JND4135 shows tumor growth inhibition activity in the BaF3-CD74-TRKA-G667C mouse xenograft model.

Pan-Trk-IN-3 (Compound 11g) is a potent inhibitor of pan-Trk and their drug-resistant mutants with IC₅₀ values of 2, 3, 2, 21, 26, 5, 7 and 6 nM against TrkA, TrkB, TrkC, TrkA^G595R, TrkA^G667C, TrkA^G667S, TrkA^F589L and TrkC^G623R, respectively. Pan-Trk-IN-3 displays excellent antitumor activity and induces apoptosis.

IHMT-TRK-284 (Compound 34) is a potent, orally active type II TRK kinase inhibitor with IC₅₀ values of 10.5, 0.7, and 2.6 nM to TRKA, B, and C respectively. IHMT-TRK-284 displays great selectivity profile in the kinome and good in vivo antitumor efficacies.

NMS-P626 is an inhibitor of TRKA, TRKB, and TRKC, with IC₅₀ values of 8 nM, 7 nM, and 3 nM, respectively. NMS-P626 inhibits the growth of KM12 cells by suppressing the phosphorylation of TPM3-TRKA and downstream signaling in KM12 cells, with an IC₅₀ of 19 nM for KM12 cells. NMS-P626 can be used in colorectal cancer research.