trka

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

SP600125 (JNK Inhibitor II) is a JNK inhibitor that inhibits JNK1, JNK2, and JNK3 (IC50=40/40/90 nM) with oral potency, reversibility, and ATP-competitive properties. SP600125 inhibits autophagy and induces apoptosis.

Trk-IN-4 (PF-6683324) is a potent pan-Trk inhibitor with IC50 = 1.1~2.6 nM for TrkA/TrkB/TrkC and antinociceptive effects. It is also a selective type II PTK6 inhibitor with IC50 = 76 nM and has antitumor effects.

CG 428 is a potent tropomyosin receptor Kinase (TRK) Degrader (uSMITETM) with a DC50 of 0.36 nM. CG 428 comprises an analog of the pan-TRK inhibitor GNF-8625 joined by a linker to the cereblon E3 ligase ligand pomalidomide. CG 428 shows selectivity for TRKA over TRKC and TRKB with Kds of 1nM, 4.2 nM, and 28 nM. CG 428 inhibits the growth of KM12 colon cancer cells with an IC50 of 2.9 nM.

ALE-0540 is a nonpeptidic heterocyclic molecule that inhibits the binding of NGF to p75 and TrkA, as well as signal transduction and biological responses mediated by TrkA receptors.

Entrectinib (RXDX-101) is a Trk, ROS1, and ALK inhibitor that inhibits TrkA, TrkB, TrkC, ROS1, and ALK (IC50=1/3/5/12/7 nM) with oral activity and blood-brain-barrier penetration. Entrectinib exhibits both antitumor and CNS activity.

Tepotinib (EMD-1214063) is a c-MET tyrosine kinase inhibitor (IC50=3 nM) that is selective, orally active, and ATP-competitive. Tepotinib has antitumor effect and is used in the treatment of non-small cell lung cancer.

DS-1205 is a potent and selective inhibitor of AXL kinase, with an IC50 of 1.3 nM. DS-1205 also inhibits MER, MET, and TRKA, with IC50s of 63, 104, and 407 nM, respectively. DS-1205 can inhibit cell migration in vitro and tumor growth in vivo[1].

JTE-952 is a oral, potent active and selective Type II inhibitor of colony stimulating factor-1 receptor (CSF-1R or cFMS, type III receptor tyrosine kinase), with IC50 values of 13 nM and 261 nM for CSF1R and TrkA , respectively. Effective against a mouse

RIPK1-IN-7 is a potent and selective inhibitor of RIPK1 (Kd of 4 nM and enzymatic IC50 of 11 nM), exhibiting excellent antimetastasis activity in the experimental B16 melanoma lung metastasis model.

Sitravatinib malate is an orally bioavailable receptor inhibitor of tyrosine kinase (RTK) (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.) , shows potent single-agent antitumor efficacy and enhances the activity of PD-1 blockade through promoting an antitumor immune microenvironment.

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

AZ-23 is an inhibitor of ATP-competitive and Trk kinase A/B/C. For TrkA, TrkB, FGFR1, Flt3, Ret, MuSk, Lck, the IC50s values are 2 nM, 8 nM, 24 nM, 52 nM, 55 nM, 84 nM, 99 nM, respectively.

CE-245677 is a potent, reversible inhibitor of Tie2 and TrkA/B kinases, with cellular IC50 values of 4.7 nM and 1 nM, respectively.

Lestaurtinib (CEP 701) is an orally available and selective inhibitor of FMS-like tyrosine kinase-3 (FLT3, IC50: 0.9 nM), which inhibits FLT3 autophosphorylation in vitro.Lestaurtinib promotes the expression of c-MYC, inhibits the phosphorylation of RPTKs, and has high affinity for TrkA and JAK2. Lestaurtinib promotes c-MYC expression, inhibits phosphorylation of RPTKs, has a high affinity for TrkA and JAK2, induces apoptosis and cell growth arrest, and can be used to study leukemia.

Ro 08-2750 is a non-peptide, reversible nerve growth factor (NGF) inhibitor that binds to NGF with an IC50 of approximately 1 µM. It is also a selective MSI RNA-binding activity inhibitor, exhibiting an IC50 of 2.7 μM. Additionally, Ro 08-2750 selectively inhibits NGF binding to p75NTR over TRKA.

Tavilermide (MIM-D3) is a selective TrkA agonist, a cyclic mimetic, which can be used to study dry keratoconjunctivitis and dry eye syndrome.

PF-06737007 is an effective inhibitor of pan-Trk in cell-based assays (IC50s: 7.7 nM, 15 nM, and 3.9 nM for TrkA, TrkB, and TrkC, respectively).

PF-06273340 is an effective, Selective, and Peripherally Restricted Pan-Trk inhibitor (IC50: Trk-A = 6 nM; Trk-B = 4 nM; Trk-C = 3 nM). PF-06273340 has low metabolic turnover in HLM and hHep is a good substrate for efflux transporters P-gp (ER = 35.7) and BCRP (ER = 4.0) and has moderate passive permeability (RRCK Papp = 5.4 × 10 6 cm s 1).

Altiratinib (DCC-2701)(DCC-2701) is a novel c-MET/TIE-2/VEGFR inhibitor; effectively reduce tumor burden in vivo and block c-MET pTyr(1349)-mediated signaling, cell growth and migration as compared with an HGF antagonist in vitro.

Danusertib (PHA-739358) is a small-molecule 3-aminopyrazole derivative with potential antineoplastic activity. Danusertib binds to and inhibits the Aurora kinases, which may result in cell growth arrest and apoptosis in tumor cells in which Aurora kinases are overexpressed.

Taletrectinib (AB-106) is a new-generation selective inhibitor of ROS1/NTRK including ROS1,NTRK1,NTRK2 and NTRK3 with IC50 of 0.207 nM,0.622 nM,2.28 nM and 0.980 nM, respectively.

Dual IGF-1R/InsR Inhibitor BMS-754807 is an oral small molecule inhibitor of insulin-like growth factor 1 receptor (IGF-1R) and insulin receptor (InsR) tyrosine kinases with potential antineoplastic activity.

Sitravatinib (MGCD516) is an inhibitor targeting multiple RTKs involved in driving sarcoma cell growth, including c-Met, c-Kit, PDGFRα/β, PDGFR, and Axl.