EGFR Degrader

Petosemtamab (MCLA 158) is an anti- EGFR (K_d: 0.22 nM) and anti-LGR5 (K_d: 0.86 nM) monoclonal antibody (mAb). Petosemtamab leads to EGFR signaling blockade and receptor degradation in LGR5+ cancer cells. Petosemtamab can be used in the research of solid tumors, such as head and neck squamous cell carcinoma (HNSCC), metastatic colorectal cancer (CRC).

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.

SJF-1521 is a selective EGFR PROTAC degrader. SJF-1521 is capable of inducing EGFR degradation in OVCAR8 cells. SJF-1521 can be used for tumor research.

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.

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

SIAIS164018 hydrochloride is a multi-kinase (ALK, EGFR, FAK, PYK2, PTK6) PROTAC degrader, with IC₅₀ values of 2.5 nM and 6.6 nM against ALK and ALK (G1202R), respectively. SIAIS164018 hydrochloride promotes the ubiquitination and degradation of ALK, EGFR, FAK, PYK2 and PTK6. SIAIS164018 hydrochloride induces cell cycle arrest at the G1 phase and triggers cell Apoptosis. SIAIS164018 hydrochloride exhibits preferential inhibitory activity against FER kinase. SIAIS164018 hydrochloride can be used in research related to non-small cell lung cancer, ovarian cancer and triple-negative breast cancer.

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 Her3 Degrader-8 (Compound PP2) is a Her3 PROTAC degrader. PROTAC Her3 Degrader-8 promotes the ubiquitination and degradation of Her3. PROTAC Her3 Degrader-8 can be used in the study of lung adenocarcinoma and ovarian cancer.

PROTAC EGFR degrader 8 (T-184) is a PROTAC degrader that targets EGFR for degradation by recruiting cereblon. 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-mutated non-small cell lung cancer cells and can be used in studies related to non-small cell lung cancer.

PROTAC EGFR degrader 4 is an EGFR^del19 and EGFR^L858R/T790M degrader with anti-proliferative activity. PROTAC EGFR degrader 4 induces degradation of mutant EGFR variants via ubiquitination and autophagy. PROTAC EGFR degrader 4 suppresses EGFR pathway signal transduction. PROTAC EGFR degrader 4 induces apoptosis, arrests cell cycle, and suppresses cell colony formation in cancer cells. PROTAC EGFR degrader 4 can be used for the research of non-small cell lung cancer.

PROTAC EGFR degrader 14 is a potent and selective EGFR PROTACdegrader with a DC₅₀ of about 2.9 nM and a D_max of 93.1% for EGFR ^{L858R/T790M/C797S}. PROTAC EGFR degrader 14 selectively induces EGFR^C797S degradation through a VHL and proteasome-dependent manner and downregulated EGFR-associated transcriptome and exhibits good selectivity over EGFR^WT. PROTAC EGFR degrader 14 induces cell cycle arrest and apoptosis and significantly inhibits tumor growth. PROTAC EGFR degrader 14 can be used for the study of nonsmall cell lung cancer (NSCLC).

PROTAC EGFR degrader 11 (Compound B71) is a PROTAC degrader for epidermal growth factor receptor (EGFR), with DC₅₀ <100 nM. PROTAC EGFR degrader 11 binds CRBN-DDB1 with a K_i of 36 nM. PROTAC EGFR degrader 11 degrades EGFR, focal adhesion kinase (FAK), and RSK1, inhibits the proliferation of BaF3 wild type and EGFR mutants, with IC₅₀ <100 nM.

PROTAC HER2 degrader-1 is a highly selective HER2 PROTAC degrader, with a DC₅₀ of 69 nM and a D_max of 96%. PROTAC HER2 degrader-1 inhibits HER2-positive cell proliferation and tumor growth through persistent HER2 degradation and potent inhibition of downstream pathways (AKT and ERK). PROTAC HER2 degrader-1 induces apoptosis in BT-474 cells. PROTAC HER2 degrader-1 can be used for research of HER2-positive cancers.

PROTAC EGFR degrader 15 is a Pomalidomide (HY-10984)-based Gefitinib (HY-50895) EGFR PROTAC degrader. PROTAC EGFR degrader 15 triggers EGFR degradation via ubiquitin-proteasome-dependent proteolysis and autophagy-lysosome activation pathways. PROTAC EGFR degrader 15 targets ETFA to enhance ATP production. PROTAC EGFR degrader 15 significantly suppresses tumor growth in a Gefitinib-acquired resistant HCC-827 xenograft model. PROTAC EGFR degrader 15 can be used for the study of non-small cell lung cancer (NSCLC).

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).

DDC-01-163 is an allosteric PROTAC degrader targeting EGFR. DDC-01-163 is dependent on the ubiquitin–proteasome system. DDC-01-163 can selectively inhibit the proliferation of L858R/T790M (L/T) mutant Ba/F3 cells. DDC-01-163 is effective against Osimertinib (HY-15772)-resistant cells with L/T/C797S and L/T/L718Q EGFR mutations. DDC-01-163 exhibits enhanced anti-proliferative activity against L858R/T790M EGFR-Ba/F3 cells when combined with the ATP-site EGFR inhibitor Osimertinib. DDC-01-163 can be used for the study of non-small cell lung cancer.