MAP4K Degrader

SB1-G-187 is a multi-target kinase PROTAC degrader with activity against various kinases including GCK, YES1, IRAK1 and LYN. SB1-G-187 induces degradation of target kinases via a p97-dependent pathway, and forms ternary complexes with CRBN and specific functional kinases. SB1-G-187 can be used in tumor-related research.

PROTAC HPK1 Degrader-1 (Compound B1) is a potent HPK1 degrader with DC₅₀ value of 1.8 nM. PROTAC HPK1 Degrader-1 inhibits phosphorylation of the SLP76 protein with IC₅₀ value of 496.1 nM. PROTAC HPK1 Degrader-1 is a bona fide HPK1-PROTAC degrader, which provided a potential tool for further HPK1 investigation in TCR signaling.

DB-0646, a PROTAC, is a multi-kinase degrader, capable of effectively degrading GCK/MAP4K2 and Yes proteins.

PROTAC HPK1 Degrader-5 is a potent and orally active HPK1 PROTAC degrader (DC50 = 5.0 nM; Dmax ≥ 99%). PROTAC HPK1 Degrader-5 significantly inhibits SLP76 phosphorylation and enhanced ERK pathway activation through degrading HPK1, thereby stimulating IL-2 and IFN-γ release. PROTAC HPK1 Degrader-5 exhibits the ability to overcome the immunosuppressive effects imposed by PGE2, NECA or TGF-β. PROTAC HPK1 Degrader-5 alone efficaciously inhibits tumor growth in an MC38 syngeneic mouse model. PROTAC HPK1 Degrader-5 can be used for the study of tumor (such as colorectal cancer) immunotherapy.

DD205-291 is an orally active PROTAC HPK1 degrader, with a DC₅₀ value of 5.3 nM. DD205-291 inhibits SLP-76 phosphorylation and induces IL-2 and IFN-γ expression (Pink: HPK1 protein ligand HY-168283; E3+linker: HY-168284; Blue: E3: HY-W115490; Black: linker: HY-W210252).

PROTAC HPK1 Degrader-2 (compound 3) is a PROTAC degrader of HPK1, with the DC₅₀ of 23 nM in human PBMC. PROTAC HPK1 Degrader-2 plays an important role in cancer research.

PROTAC HPK1 Degrader-8 is a HPK1 PROTAC degrader with a DC₅₀ of 1-10 nM. PROTAC HPK1 Degrader-8 promotes HPK1 ubiquitination and degradation. PROTAC HPK1 Degrader-8 induces IL-2 production, with an EC₅₀ of 3 nM. PROTAC HPK1 Degrader-8 can be used in research related to hematologic malignancies and solid tumors.

PROTAC HPK1 Degrader-4 (compound E3) is a selective and orally active PROTAC HPK1 degrader with a DC₅₀ of 3.16 nM. PROTAC HPK1 Degrader-4 demonstrates >1000-fold selectivity over GLK. PROTAC HPK1 Degrader-4 promotes immune activation. PROTAC HPK1 Degrader-4 can be used for the study of colon cancer and lymphoma (Pink: ligand for target protein (HY-174355); Blue: ligand for E3 ligase CRBN (HY-45808); Black: Linker (HY-174356); Target protein ligand-linker Conjugate (HY-174357)).

PROTAC HPK1 Degrader-6 (314) is a highly efficient and effective PROTAC degrader targeting HPK1 (IC₅₀ ＜ 50 nM). PROTAC HPK1 Degrader-6 can be used for the study of leukemia. Red: HPK1 ligand (HY-179196); Blue: E3 ligase CRBN ligand (HY-179197).