TrkA 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.

TIY-7 is a selective and orally active tropomyosin receptor kinase (TRK) inhibitor. TIY-7 shows enzyme inhibitory activity with IC₅₀s of 2.9, 1.1, 0.7, 0.8, 0.8, 0.2 nM for TRKA, TRKA^G595R, TRKA^G667C, TRKA^F589L, TRKC^G623R, TRKC^G696A, respectively. TIY-7 shows anti-tumor potency in mouse xenograft model.

Protein kinase inhibitor 5 sulfate hydrate is a potent TRK-A inhibitor with an IC₅₀ value of 1.8 nM. Protein kinase inhibitor 5 sulfate hydrate inhibits cell viability.

Multi-kinase-IN-7 is a multikinase inhibitor with IC₅₀s of 2.19, 2.95, 3.59 and 9.31 μM against EGFR, VEGFR2, TrKA and CDK2, respectively. Multi-kinase-IN-7 shows moderate and weaker activity against FAK, AKT1, GSK3β and CDK5 with IC₅₀ values of 6.3, 9.2, 11.7 and 23.4 μM, respectively. Multi-kinase-IN-7 displays broad spectrum anti­proliferative potential against NCI cancer cell lines. Multi-kinase-IN-7 induces cell cycle arrest, apoptosis and necrosis. Multi-kinase-IN-7 Inhibitor can be used for the study of breast cancer.

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.

Protein kinase inhibitor 5 is a potent TRK-A inhibitor with an IC₅₀ value of 1.8 nM. Protein kinase inhibitor 5 inhibits cell viability.

Trk-IN-11 (Compound 14h) is a potent inhibitor of TRK (IC₅₀ = 1.4, 1.8 nM, against TrkA, TrkA^G595R, respectively). As a receptor tyrosine kinase (RTK), tropomyosin receptor kinase (Trk) is a key agent target in solid tumors. Trk-IN-11 has the potential for the research of cancer disease.

(R)-Larotrectinib is a potent TRK inhibitor with an IC₅₀ value of 28.5 nM for TrkA. (R)-Larotrectinib can be used for researching cancer, inflammatory and certain infectious diseases

Trk-IN-10 (Compound 14j) is a potent inhibitor of TRK (IC₅₀ = 0.86, 6.92 nM, against TrkA, TrkA^G595R, respectively). As a receptor tyrosine kinase (RTK), tropomyosin receptor kinase (Trk) is a key agent target in solid tumors. Trk-IN-10 (IC₅₀ = 350 nM against ALK) has a higher selectivity of Trk inhibition, which may be of great significance for reducing toxicity.

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.

Multi-kinase-IN-6 (compound 10e) is a multikinase inhibitor that shows good enzyme inhibitory activity against TrkA, ALK2, c-KIT, EGFR, PIM1, CK2α, CHK1, and CDK2. Multi-kinase-IN-6 reveals antiproliferative activity against MCF7, HCT116 and EKVX with IC₅₀ values of 3.36 μM, 1.40 μM and 3.49 μM, respectively. Multi-kinase-IN-6 shows cell cycle arrest at the G1/S phase and G1 phase in MCF7 and HCT116 cells with good apoptotic effect.

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.

TRK-IN-34 is an orally active TRKand TRKC mutant kinase inhibitor, with IC₅₀ values of 0.75 nM and 0.96 nM against TRKA^G595R and TRKA^G667C, respectively. TRK-IN-34 inhibits the kinase activities of TRKA^G595R and TRKA^G667C at the functional level. TRK-IN-34 inhibits the proliferation of TRKA-transfected cells, exerts tumor growth-inhibitory effects and achieves partial tumor regression in xenograft models. TRK-IN-34 can be used to study TRK inhibitor-resistant cancers driven by the TRKA^G667C mutation.

NPA101.3 is an orally active RET receptor tyrosine kinase and VEGFR2 inhibitor (RET IC₅₀ = 0.001 μM, RET^V804M IC₅₀ = 0.008 μM, VEGFR2 IC₅₀ = 0.003 μM). NPA101.3 inhibits purified TRKA (IC₅₀ = 32 nM) and CSF1R (IC₅₀ = 46 nM). NPA101.3 completely suppresses tumor formation in RET^/C634Y-transformed cells and also attenuates tumor formation in HRAS^/G12V-transformed cells. NPA101.3 can be used in the research of RET-driven cancers.

Type II TRK inhibitor 1 is a potent TRK inhibitor, which inhibits various TRK fusion protein variants and wild type. Type II TRK inhibitor 1 exhibits antiproliferative activity against Ba/F3 cells harboring CD74-TRKA^G667C and ETV6-TRKC^G696C fusion proteins with IC₅₀s of 6 nM and 1.7 nM, respectively. Type II TRK inhibitor 1 is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.

D5261 is a potent, type III allosteric tropomyosin-related kinase A (TrkA) inhibitor.

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.

TRK-IN-33 is a TRK inhibitor. TRK-IN-33 exhibits excellent TRKA^G667C degradation (DC₅₀ = 24.69 nM; D_max > 90%), while sparing the wild-type protein in virto. TRK-IN-33 shows antiproliferative activities against Ba/F3-LMNA-NTRK1^G667C cells with an IC₅₀ value of 2.48 nM. TRK-IN-33 effectively inhibits tumor growth and enhances apoptosis in tumor tissues with no apparent toxicity in vivio. TRK-IN-33 can be used for NTRK fusion−positive cancers research.

Anizatrectinib (hTrkA-IN-1) is an orally active and blood-brain barrier-penetrant TrkA kinase/hERG channel inhibitor. Anizatrectinib can be used for research on TrkA-mediated related diseases, such as pain, cancer, inflammation, and inflammatory diseases.