EGFR Degrader

Becotatug vedotin (MRG003) is an Antibody-Drug Conjugate (ADC) that consists of an anti-EGFR humanized IgG1 monoclonal antibody Becotatug (HY-P990049) and MMAE (HY-15162). These two parts are connected through a valine-citrulline (valine-citrulline) linker, where the linker and MMAE constitute the ADC's Drug-Linker conjugate VcMMAE (HY-15575).

HJM-561 is a selective and effective orally active EGFR PROTAC degrader. HJM-561 is able to overcome the triple EGFR mutations that are resistant to Osimertinib (HY-15772). HJM-561 exhibits potent degradation of EGFR Del19/T790M/C797S (DC₅₀: 9.2 nM) and L858R/T790M/C797S (DC₅₀: 5.8 nM), and has anti-tumor activity (pink: EGFR ligand (HY-12857); blue: CRBN ligand (HY-A0003); black: linker).

SJF-1528 (PROTAC 1) is a potent EGFR PROTAC degrader with DC₅₀ values of 39.2 nM and 736.2 nM for wild-type EGFR in OVCAR8 cells and Exon 20 Ins mutant EGFR in HeLa cells. SJF-1528 also degrades HER2. SJF-1528 promotes ubiquitination and degradation of EGFR and can be used in breast cancer research.

HyT36 is a low molecular weight hydrophobic tag that promotes the degradation of fusion protein and pseudokinase Her3.

MS39 (compound 6) is a PROTAC targeting EGFR. MS39 reduces the expression of EGFR and downstream signaling in HCC-827 and H3255 cells. MS39 inhibits the proliferation of H3255 cells.

MS9427 TFA is a potent PROTAC EGFR degrader with K_ds of 7.1 nM and 4.3 nM for EGFR WT and EGFR L858R, respectively. MS9427 TFA selectively degrades the mutant but not the WT EGFR through both the ubiquitin/proteasome system (UPS) and autophagy/lysosome pathways. MS9427 TFA potently inhibits the proliferation of NSCLC cells. MS9427 TFA can be used for researching anticancer.

PROTAC EGFR degrader 8 (T-184) is a PROTAC degrader that targets EGFR for degradation by recruiting cereblon. It induces EGFR protein degradation with a DC₅₀ of 10.18 nM. The IC₅₀ values of PROTAC EGFR degrader 8 for inhibiting the growth of H1975, PC-9 and HCC827 cells are 7.72, 121.9 and 14.21 nM, respectively. PROTAC EGFR degrader 8 inhibits the proliferation of EGFR-mutant non-small cell lung cancer cells and can be used in studies related to non-small cell lung cancer.

SJF-1528 (PROTAC 1) hemihydrate is a potent EGFR PROTAC degrader with DC₅₀ values of 39.2 nM and 736.2 nM for wild-type EGFR in OVCAR8 cells and Exon 20 Ins mutant EGFR in HeLa cells. SJF-1528 hemihydrate also degrades HER2. SJF-1528 hemihydrate promotes ubiquitination and degradation of EGFR and can be used in breast cancer research.

Petosemtamab (FUT8-KO) is an anti-EGFR and anti-LGR5 monoclonal antibody expressed in CHO cells with the fucosyltransferase 8 gene (FUT8) knocked out. Fucosyl loss enhances the ADCC effect of the antibody. Petosemtamab (FUT8-KO) leads to EGFR signaling blockade and receptor degradation in LGR5+ cancer cells. Petosemtamab (FUT8-KO) can be used for research on solid tumors such as head and neck squamous cell carcinoma (HNSCC) and metastatic colorectal cancer (CRC).

PROTAC EGFR degrader 7 (compound 13b) diTFA is a potent and selective CRBN-recruiting PROTAC EGFR^L858R/T790M degrader, with a DC₅₀ of 13.2 nM. PROTAC EGFR degrader 7 diTFA inhibits NCI–H1975 cells proliferation, with an IC₅₀ of 46.82 nM. PROTAC EGFR degrader 7 diTFA significantly induces apoptosis and G2/M phase arrest in NCI–H1975 cell. PROTAC EGFR degrader 7 diTFA shows antitumor activity, and can be used for non-small cell lung cancer (NSCLC) research. PROTAC EGFR degrader 7 diTFA is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.

CZY43 is a HER3 degrader. CZY43 can effectively induce HER3 degradation in a dose- and time-dependent manner in breast cancer SKBR3 cells. CZY43 potently inhibits HER3-dependent signaling and cancer cell growth and outperforms Bosutinib (HY-10158).

ZSH-2117 is a covalent and selective EGFR PROTAC degrader with a DC₅₀ of 45 nM in Ba/F3-EGFR^{L858R/T790M/C797S} cells. ZSH-2117 significantly inhibits cell proliferation and reduces the downstream EGFR signaling proteins level of AKT and ERK. ZSH-2117 effectively inhibits tumor growth in Ba/F3-EGFR^{L858R/T790M/C797S} xenograft mice model.

Pro-PEG3-BA is an EML4-ALK/EGFR PROTAC degrader, degrading EML4 ALK and EGFR mutant (L858R/T790M) with DC₅₀ values of 0.42 and 13.50 μM, respectively. Pro-PEG3-BA hinders proliferation and induces cell cycle arrest and apoptosis of NSCLC cells in vitro. Pro-PEG3-BA shows safety profile and decreases EML4-ALK protein via rewiring the ubiquitin- proteasome system in vivo. Pro-PEG3-BA can be used for non-small cell lung cancer research.

KRAS G12D inhibitor 25 (Compound 148) is an inhibitor for KRAS G12C and HSP90α with IC₅₀ of < 0.1 μM and 0.1-1 μM, respectively. KRAS G12D inhibitor 25 inhibits the proliferation of MIA PaCa-2 and NCI-H358 with EC₅₀ of < 0.1 μM and 0.1-1 μM, respectively. KRAS G12D inhibitor 25 degrades ERBB2 with a DC₅₀ of 0.1-1 μM.

(Rac)-Zearalanone-d₆ is the d₆-labeled (Rac)-Zearalanone (HY-N6678A). (Rac)-Zearalanone is an ATP-competitive HSP90 inhibitor with an EC₅₀ of 2.3 μM. (Rac)-Zearalanone interferes with the binding of ATP to HSP90, impairs the chaperone function of HSP90, and promotes the degradation of client proteins. (Rac)-Zearalanone reduces intracellular accumulation of Raf-1, induces cleavage of caspase-3, and promotes Her2 degradation in a dose-dependent manner by disrupting the Her2-HSP90 interaction. (Rac)-Zearalanone can be used in the research of small cell lung cancer and breast cancer.

EGFR ligand-18 is a PROTAC target protein ligand that can be used for synthesis of PROTACs, such as PROTAC EGFR degrader 16 (HY-178242). PROTAC EGFR degrader 16 is a potent EGFR PROTAC degrader with anti-tumor activity.

Lys-PEG3-BA is an EML4-ALK/EGFR PROTAC degrader with DC₅₀ values of 1.32 and 19.66 μM for H3122 (EML4-ALK) and H1975 (EGFR-L858R/T790M) cells, respectively. Lys-PEG3-BA hinders proliferation via rewiring the ubiquitin- proteasome system in vitro. Lys-PEG3-BA can be used for non-small cell lung cancer research.

PROTAC EGFR degrader 12 (example 1) is a PROTAC degrader targeting EGFR that can effectively degrade EGFR mutants, but has little effect on EGFR WT. PROTAC EGFR degrader 12 shows IC_{50s against EGFR^L858R-T790M (NCI-H1975 cells), EGFR^L858R (NCI-H3255 cells), and EGFR^{L858R-T790M-L797S} (NCI-H1975+CS cells) of all <50 nM.}

SST0116CL1 is a HSP90 inhibitor (IC₅₀: 0.21 μM). SST0116CL1 binds to the ATP binding pocket of Hsp90, and interferes with Hsp90 chaperone function thus resulting in client protein (EGFR, CDK4 and AKT) degradation. SST0116CL1 induces degradation of Her2 in BT-474 cell (IC₅₀: 0.2 μM). SST0116CL1 has antiproliferative activity and inhibits tumor growth. SST0116CL1 can be used for the study of leukemia, gastric and ovarian carcinoma.

Gly-PEG3-BA is an EML4-ALK PROTAC degrader. Gly-PEG3-BA effectively reduces EML4-ALK with a DC₅₀ value of 0.50 μM in H3122 (EML4-ALK) cells. Gly-PEG3-BA effectively reduces EGFR mutant (L858R/T790M) levels with a DC₅₀ of 20.15 μM in H1975 (EGER-L858R/T790M) cells. Gly-PEG3-BA exerts potent antiproliferation activity in H3122 (EML4-ALK) and H1975 (EGER-L858R/T790M) cells with IC₅₀s value of 0.84 and 20.74 μM. Gly-PEG3-BA can be used for non-small lung cancer research.