EGFR Degrader

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.

MS9427 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 selectively degrades the mutant but not the WT EGFR through both the ubiquitin/proteasome system (UPS) and autophagy/lysosome pathways. MS9427 potently inhibits the proliferation of NSCLC cells. MS9427 can be used for researching anticancer.

SIAIS164018 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 promotes the ubiquitination and degradation of ALK, EGFR, FAK, PYK2 and PTK6. SIAIS164018 induces cell cycle arrest at the G1 phase and triggers cell Apoptosis. SIAIS164018 exhibits preferential inhibitory activity against FER kinase. SIAIS164018 can be used in research related to non-small cell lung cancer, ovarian cancer and triple-negative breast cancer.

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.

Herbimycin A is an antibiotic and protein tyrosine kinase inhibitor. Herbimycin A directly inhibits the autophosphorylation of p210 BCR-ABL with an IC₅₀ of approximately 5 μM, and reduces Src kinase activity. Herbimycin A also induces the degradation of receptor tyrosine kinases such as insulin-like growth factor 1 receptor (IGF-1R), insulin receptor (IR) and epidermal growth factor receptor (EGFR) via the ubiquitin-20S proteasome pathway. Herbimycin A directly modifies NF-κB p50, with the main target site involving Cys62, thereby blocking the DNA binding of p50 and NF-κB-driven gene expression. Herbimycin A can be used in studies related to tyrosine kinase signaling, chronic myeloid leukemia, NF-κB signaling, osteoclast function, apoptosis and cellular stress.

TX2-121-1 is a bifunctional hydrophobic tag Her3 degrader and also a Her3 inhibitor with an IC₅₀ of 49 nM. TX2-121-1 covalently binds to Cys721 of Her3, induces Her3 degradation via the Hsp70/Hsp90-assisted proteasomal pathway, interferes with the heterodimerization of Her3 with Her2/c-Met, and attenuates downstream Erk/Akt signaling, thereby inhibiting Her3-dependent cancer cell growth. TX2-121-1 can be used for the research of non-small cell lung cancer, ovarian cancer and Her3-driven breast cancer.

PROTAC EGFR degrader 18 is a VHL-based PROTAC degrader targeting EGFR. PROTAC EGFR degrader 18 inhibits tumor cell proliferation and induces apoptosis. When functionalized with hyaluronic acid, PROTAC EGFR degrader 18 achieves specific enrichment at tumor sites via CD44-mediated targeting, exerting anti-tumor activity while significantly reducing systemic toxicity. PROTAC EGFR degrader 18 can be used for the research of non-small cell lung cancer.

CZY43 is a HER3 degrader with a DC₅₀ of 559 nM. CZY43 induces HER3 degradation via autophagy, inhibits HER3-dependent signaling pathways, suppresses downstream PI3K/Akt signaling, and thereby inhibits tumor cell proliferation and cell adhesion. CZY43 can be used in studies of breast cancer and non-small cell lung cancer.

COVA208 is a bispecific FynomAb (a fusion protein of an antibody and a Fyn SH3-derived binding protein) that targets HER2. COVA208 induces the degradation of HER2, reduces the levels of HER2, HER3, and EGFR, thereby effectively blocking the downstream signaling pathways of HER2, including the HER3-PI3K-AKT and MAPK pathways, and simultaneously inducing apoptosis of tumor cells. COVA208 is promising for research of cancers, such as HER2-positive breast cancer, gastric cancer, and colorectal cancer.

ZSH-2117 is an NEDD4-recruiting EGFR PROTAC degrader. ZSH-2117 shows an IC₅₀ of 13 nM against EGFR^{L858R/T790M/C797S}, induces EGFR proteasome-dependent degradation, inhibits the downstream signaling pathways of EGFR, including the phosphorylation of AKT and ERK, suppresses cancer cell proliferation, and exhibits in vivo anti-tumor activity. ZSH-2117 can be used in research related to non-small cell lung cancer.

HSP90-IN-11 is a HSP90 inhibitor with an IC₅₀ of 27.8 nM. HSP90-IN-11 inhibits the activity of HSP90, which in turn induces rapid degradation of EGFR and Akt proteins in non-small cell lung cancer (NSCLC) cells. HSP90-IN-11 induces accumulation of the G1 subphase cell population in NSCLC cells, activates caspase-3, caspase-8, caspase-9 and PARP, thereby triggering apoptosis. HSP90-IN-11 exhibits antiproliferative activity in colorectal cancer and NSCLC cells. HSP90-IN-11 can be used for the research of colorectal cancer and non-small cell lung cancer.

PROTAC EGFR degrader 5 is a PROTAC EGFR degrader, potently degrades EGFR^Del19 in HCC827 cells with the DC₅₀ of 34.8 nM. PROTAC EGFR degrader 5 significantly induces the apoptosis of HCC827 cells and arrest the cells in G1 phase.

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.

PROTAC EGFR degrader 16 is a selective EGFR PROTAC degrader with a DC₅₀ value of < 50 nM. PROTAC EGFR degrader 16 can be used for the study of EGFR-driven cancerssuch as non-small cell lung cancer.

TX2-120-1 possesses the ability to bind to Her3, with an IC₅₀ value of 56 nM for Her3. TX2-120-1 can be used for the synthesis of TX2-121-1 (HY-118998).

FS102 is a selective Fc fragment with antigen binding (Fcab) that targets HER2 with a K_D value of 0.8 nM. FS102 induces the degradation of HER2, activates Caspase 3/7 and disrupts the integrity of the cell membrane, triggering apoptosis of tumor cells. FS102 is promising for research of cancers such as breast cancer, gastric cancer, and colorectal cancer.

PROTAC EGFR degrader 19 is a potent EGFR PROTAC degrader. PROTAC EGFR degrader 19 bridges EGFR and VHL E3 ligase, thereby promoting ubiquitination and degradation of EGFR, which in turn blocks oncogenic signaling pathways. PROTAC EGFR degrader 19 can be used for research on non-small cell lung cancer.

PROTAC EGFR degrader 10 (Compound B56) is a PROTAC degrader for epidermal growth factor receptor (EGFR), with DC₅₀ <100 nM. PROTAC EGFR degrader 10 binds CRBN-DDB1 with a K_i of 37 nM. PROTAC EGFR degrader 10 degrades EGFR, focal adhesion kinase (FAK), and RSK1, inhibits the proliferation of BaF3 wild type and EGFR mutants, with IC₅₀ <150 nM.

EGFR AUTOTAC-1 is a p62/SQSTM1-directed EGFR AUTOTAC degrader. EGFR AUTOTAC-1 recruits p62 to form a ternary complex, activates the ubiquitin-proteasome system-independent Atg5-dependent autophagy-lysosome pathway, mediates autophagic degradation of EGFR and inhibits the AKT/ERK signaling pathway, thereby promoting apoptosis and activating autophagy. EGFR AUTOTAC-1 can be used for the research of non-small cell lung cancer.(Pink: EGFR ligand (HY-79511); Blue: p62 ligand (HY-187557); Black: Linker)