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 PROTAC degrader that recruits cereblon to induce HPK1 degradation, with a DC₅₀ of 1.8 nM. PROTAC HPK1 Degrader-1 inhibits HPK1 kinase activity, with an IC₅₀ of 140.5 nM. PROTAC HPK1 Degrader-1 suppresses the phosphorylation of SLP76 protein, with an IC₅₀ of 496.1 nM. PROTAC HPK1 Degrader-1 can be used to investigate non-kinase-dependent signaling of HPK1 in the TCR pathway and cancer-related research.

PROTAC HPK1 Degrader-3 is an orally active HPK1 PROTAC degrader with a DC₅₀ of 21.26 nM. PROTAC HPK1 Degrader-3 induces HPK1 degradation via the ubiquitin-proteasome system and forms a stable ternary complex with HPK1 and CRBN. PROTAC HPK1 Degrader-3 inhibits the SLP76 and NF-κB signaling pathways, enhances the transduction of the MAPK signaling pathway, and promotes the secretion of T cell immune cytokines. PROTAC HPK1 Degrader-3 inhibits tumor growth and enhances the anti-tumor efficacy of anti-PD-L1 therapy. PROTAC HPK1 Degrader-3 can be used in the research of colon cancer.

DB-0646 is a multi-target PROTAC degrader that degrades over 125 distinct kinases in various cell lines, with its degradation process dependent on the activity of p97. DB-0646 induces ubiquitination and degradation of GCK, BUB1 and YES1.

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.

SS47 is a hematopoietic progenitor kinase HPK1 PROTAC-class degrader and immune activator. SS47 promotes the proliferation of CD4+ and CD8+ T cells as well as IFN-γ secretion, and enhances the anti-tumor cytotoxicity and in vivo efficacy of BCMA CAR-T cells. SS47 also inhibits tumor growth in mouse models, and when combined with anti-PD-1 therapy, it improves the immune response of 4T1 tumor-bearing mice. SS47 can be used in breast cancer-related research.

DD205-291 is a selective, orally active HPK1 PROTAC degrader with a DC₅₀ of 8.8 nM. By inducing complete degradation of HPK1 protein, DD205-291 simultaneously blocks both its kinase-dependent functions and non-kinase scaffold functions. DD205-291 inhibits the phosphorylation of SLP-76 with an EC₅₀ of 22.98 nM. DD205-291 induces the production of IL-2 and IFN-γ with EC₅₀ values of 34.68 nM and 32.6 nM, respectively. Combined with anti-PD1 in mouse models, DD205-291 exerts tumor-suppressive effects with favorable safety profiles. DD205-291 can be used in colon cancer-related research.

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).