RET Inhibitor

RET-IN-10 is a potent inhibitor of RET. RET loss of function mutations leads to Hirschsprung's disease, while its gain of function mutations is associated with a variety of human tumors. RET-IN-10 has the potential for the research of cancer diseases (extracted from patent WO2021135938A1, compound 18).

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.

RET-IN-11 is a potent and selective RET inhibitor with IC₅₀s of 6.20 nM, 18.68 nM for RET and RET^V804M, respectively. RET-IN-11 shows anti-proliferation and migration activity in CCDC6-RET-driven LC-2/ad cells. RET-IN-11 induces cell apoptosis.

Enbezotinib (enantiomer) (Compound 44) is the enantiomer form of Enbezotinib (HY-145565). Enbezotinib is an inhibitor of RET.

RET ligand-2 is a selective RET inhibitor. RET ligand-2 can serve as a ligand for target protein (Ligands for Target Protein for PROTAC) for the development of PROTAC RET degraders with antitumor activity. RET ligand-2 can be used for the synthesis of RD-23 (HY-168867).

HSN608 is an orally active, potent RET G810 mutant inhibitor. HSN608 inhibits G810C, G810R, G810D. HSN608 induces Apoptosis. HSN608 inhibits the Selpercatinib (HY-114370)-resistant RET(G810C) CDX tumors.

AD57 hydrochloride is an orally active multikinase inhibitor, inhibits RET, BRAF, S6K and Src.

Aurora B/RET-IN-1 is a dual RET and Aurora B inhibitor with human IC₅₀ values of 78 nM and 24 nM, respectively. Aurora B/RET-IN-1 binds the DFG-out conformation of RET as a type II inhibitor and extends into the allosteric pocket. Aurora B/RET-IN-1 inhibits Aurora B kinase activity. Aurora B/RET-IN-1 inhibits RET and Aurora B signaling pathways. Aurora B/RET-IN-1 can be used for research on non-small cell lung cancer.

CDD-2210 is a STK33 inhibitor, with a K_d of 0.1 nM and an IC₅₀ of 38 nM. CDD-2210 has relatively weak inhibitory effects on off-target kinases, with IC₅₀ values of 1209 nM for CLK1, 917 nM for CLK2, 544 nM for CLK4, and 746 nM for RET. CDD-2210 can be used for the study of contraception.

Multi-kinase-IN-5 (compound 15c) is a promising multi-kinase inhibitory agent. Multi-kinase-IN-5 inhibits a panel of protein kinases (RET, KIT, cMet, VEGFR1,2, FGFR1, PDGFR and BRAF), showing % inhibition of 74%, 31%, 62%, 40%, 73%, 74%, 59%, and 69%, respectively, and IC₅₀ of 1.287, 0.117 and 1.185 μM against FGFR1, VEGFR, and RET kinases, respectively.

VEGFR2-IN-84 is an orally active, multi-targeted tyrosine kinase inhibitor based on a naphthalene ring scaffold. VEGFR2-IN-84 inhibits VEGFR2 with sub-nanomolar affinity and broadly targets kinases including Kit, FGFR, PDGFR, and Ret. By competitively binding to the ATP-binding pocket, VEGFR2-IN-84 blocks the phosphorylation of VEGFR2 and its downstream AKT/ERK signaling pathway, thereby significantly inhibiting endothelial cell proliferation, migration, and tumor angiogenesis. VEGFR2-IN-84 exhibits broad-spectrum antiproliferative activity against various solid tumors such as liver cancer, lung cancer, and renal cancer, shows weak toxicity to normal cells, and has superior potency to Lenvatinib (HY-10981). VEGFR2-IN-84 possesses favorable pharmacokinetic properties and high safety (LD₅₀>2000 mg/kg), and can be used in related studies of various malignant tumors.

RET-IN-8 is a rearranged during transfection (RET) kinase inhibitor extracted from patent WO2021093720A1 compound I-1. RET-IN-8 can be used for the research of cancer.

CDD-2212 is a STK33 inhibitor, with a K_d of 1.9 nM and an IC₅₀ of 999 nM. CDD-2212 has relatively weak inhibitory effects on off-target kinases, with IC₅₀ values of 3223 nM for CLK1, 1555 nM for CLK2, 5884 nM for CLK4, and 1093 nM for RET. CDD-2212 can be used for the study of contraception.

Tafetinib (SIM010603) analogue 1 is an analog of the tyrosine kinase receptor inhibitor Tafetinib (SIM010603)..

ML786 is a potent and orally bioavailable Raf inhibitor, with IC₅₀s of 2.1, 4.2, and 2.5 nM for ^V600EΔB-Raf, wt B-Raf, and C-Raf, respectively. ML786 also inhibits Abl-1, DDR2, EPHA2, KDR, and RET (IC₅₀=<0.5, 7.0, 11, 6.2, 0.8 nM). ML786 can be used for the research of cancers.

Anti-GFRA4 Antibody (scFv) is a recombinant single-chain antibody fragment targeting GFRA4. Anti-GFRA4 Antibody (scFv) is formed by connecting the variable region of the heavy chain (VH) and the variable region of the light chain (VL) through a flexible short peptide (Linker), without the Fc segment, while maintaining the antigen-binding specificity.

RET-IN-30 (Compound 28) is a RET inhibitor that exhibits inhibitory activity against both wild-type RET and some of its mutants. RET-IN-30 can inhibit the proliferation of A549 cells and has anti-tumor activity.

FHND5071 (1H) is a selective inhibitor targeting the RET (rearrangement during transfection) tyrosine kinase. FHND5071 (1H) is promising for research of RET-driven cancers (such as thyroid cancer, lung cancer, etc.).

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.

RET ligand-1 is a target protein ligand targeting RET that can be used to synthesize PROTAC LDD39 (HY-159967).