TrkB Inhibitor

Larotrectinib (LOXO-101) is an ATP-competitive oral, selective inhibitor of the tropomyosin-related kinase (TRK) family receptors, with low nanomolar 50% inhibitory concentrations against all three isoforms (TRKA, B, and C).

DZX19 (Compound C02) is an orally active, selective TRK inhibitor with a TRKA IC₅₀ value of 1.32 nM, a TRKB IC₅₀ of 2.28 nM, and a TRKC IC₅₀ of 4.05 nM. DZX19 inhibits the kinase activities of wild-type TRKA, TRKA mutants (G595R, F589L, G667C), wild-type TRKB, and wild-type TRKC, and suppresses the phosphorylation of TRKA as well as its downstream AKT and ERK signaling pathways. DZX19 induces apoptosis. DZX19 inhibits tumor growth in a colorectal cancer xenograft mouse model. DZX19 is applicable for the research of colorectal 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.

Sitravatinib (MGCD516) is an orally bioavailable receptor tyrosine kinase (RTK) inhibitor with IC₅₀s of 1.5 nM, 2 nM, 2 nM, 5 nM, 6 nM, 6 nM, 8 nM, 0.5 nM, 29 nM, 5 nM, and 9 nM for Axl, MER, VEGFR3, VEGFR2, VEGFR1, KIT, FLT3, DDR2, DDR1, TRKA, TRKB, respectively. Sitravatinib shows potent single-agent antitumor efficacy and enhances the activity of PD-1 blockade through promoting an antitumor immune microenvironment.

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

GNF-5837 is a potent, selective, and orally bioavailable pan-tropomyosin receptor kinase (TRK) inhibitor which display antiproliferative effects in cellular Ba/F3 assays ( IC₅₀ values of 7 nM, 9 nM and 11 nM for cells containing the fusion proteins Tel-TrkC, Tel-TrkB and Tel-TrkA, respectively) .

Altiratinib (DCC-2701) is a multi-targeted kinase inhibitor with IC₅₀s of 2.7, 8, 9.2, 9.3, 0.85, 4.6, 0.83 nM for MET, TIE2, VEGFR2, FLT3, Trk1, Trk2, and Trk3 respectively.

Larotrectinib sulfate (LOXO-101 sulfate; ARRY-470 sulfate) is an ATP-competitive oral, selective inhibitor of the tropomyosin-related kinase (TRK) family receptors, with low nanomolar 50% inhibitory concentrations against all three isoforms (TRKA, B, and C).

AZ-23 is an ATP-competitive and orally bioavailable Trk kinase A/B/C inhibitor with IC₅₀s of 2 nM (TrkA), 8 nM (TrkB), 24 nM (FGFR1), 52 nM (Flt3), 55 nM (Ret), 84 nM (MuSk), 99 nM (Lck), respectively.

Belizatinib (TSR-011) is an orally active, potent inhibitor of ALK and TRKA, TRKB, and TRKC, with IC₅₀ of 0.7 nM for wild-type recombinant ALK kinase.

PF-6683324 (Trk-IN-4) is a potent pan-Trk inhibitor in cell-based assays with IC₅₀s of 1.9 nM, 2.6 nM and 1.1 nM for TrkA, TrkB and TrkC, respectively. Anti-hyperalgesic effect.

PF-06273340 is a peripherally restricted pan-Trk inhibitor with IC₅₀ values of 6, 4, 3 nM for TrkA, TrkB, and TrkC receptors. PF-06273340 binds in a DFG-out conformation, targeting less conserved kinase ligand binding domain regions outside the ATP binding pocket. PF-06273340 exhibits anti-hyperalgesic and analgesic effects. PF-06273340 can be used for the research of pain.

Cannflavin B is a flavonoid compound that can be isolated from Cannabis sativa L. Cannflavin B is inhibitors of PGE₂ release (IC₅₀: 0.7 μM), mPGES-1 (IC₅₀: 3.7 μM), and 5-lipoxygenase. Cannflavin B has multiple activities such as anti-inflammatory, antioxidant, anti-glycation, anti-ferroptosis, anti-tumor, and anti-Leishmania (IC₅₀: 14 μM). Cannflavin B can also inhibit the TrkB-BDNF signaling pathway.

Zurletrectinib is a brain-penetrant, orally active TRK inhibitor (TRKA IC₅₀ = 0.81 nM; TRKB IC₅₀ = 0.145 nM; TRKC IC₅₀ = 0.184 nM). Zurletrectinib exhibits stronger activity as a consequence of its augmented binding affinity for TRK kinases. Zurletrectinib exhibits higher activity against most TRK inhibitor resistance mutations (13 out of 18 mutations). Zurletrectinib can be used for the study of glioma.

PF-06737007 is a potent pan-Trk inhibitor in cell-based assays with IC₅₀s of 7.7 nM, 15 nM and 3.9 nM for TrkA, TrkB and TrkC, respectively. Anti-hyperalgesic effect.

TrkA-IN-1 is a potent and selective Tropomyosin-related kinase A (TrkA) inhibitor with an IC₅₀ of 99 nM in a cell-based assay. TrkA-IN-1 has analgesic activity.

Sitravatinib malate (MGCD516 malate) is an orally bioavailable receptor tyrosine kinase (RTK) inhibitor with IC₅₀s of 1.5 nM, 2 nM, 2 nM, 5 nM, 6 nM, 6 nM, 8 nM, 0.5 nM, 29 nM, 5 nM, and 9 nM for Axl, MER, VEGFR3, VEGFR2, VEGFR1, KIT, FLT3, DDR2, DDR1, TRKA, TRKB, respectively. Sitravatinib malate shows potent single-agent antitumor efficacy and enhances the activity of PD-1 blockade through promoting an antitumor immune microenvironment.

JYP0322 (ROS1-IN-3) is a potent orally active, selective, and CNS-penetrant ROS1 inhibitor. JYP0322 selectively inhibits human wild-type ROS1 and human ROS1^G2032R with IC₅₀s of 0.37 and 0.3 nM, respectively, showing 6-130-fold selectivity over TRKA, TRKB, and TRKC. JYP0322 inhibits proliferation of ROS1 fusion-expressing cells, and inhibits tumor growth in mouse xenograft models. JYP0322 can be used for the research of non-small cell lung cancer (NSCLC).

PF-06733804 is a potent pan-Trk inhibitor in cell-based assays with IC₅₀s of 8.4 nM, 6.2 nM and 2.2 nM for TrkA, TrkB and TrkC, respectively. Anti-hyperalgesic effect.

Trk-IN-7 (compound I-6) is a potent TRK inhibitor with IC₅₀s of ranging from 0.25-10 nM for TRKA, TRKB and TRKC, respectively. Trk-IN-7 shows inhibition against EML4-ALK (IC₅₀<15 nM) ALK G1202R, ALK C1156Y, ALK R1275Q, ALK F1174L, ALK L1197M, and ALK G1269A (IC₅₀=5-50 nM).