MAP4K1/HPK1 Inhibitor

DS21150768 is a potent, orally active HPK1 inhibitor. DS21150768 shows potent activity to enhance T-cell function. DS21150768 has anticancer effects.

ZYF0033 is an orally active inhibitor of the hematopoietic progenitor cell kinase HPK1 with an IC50 of less than 10 nM based on the phosphorylation inhibition of MBP protein. ZYF0033 promotes anti-cancer immune responses and reduces phosphorylation of SLP76 (serine 376). ZYF0033 inhibits tumor growth in the 4T-1 syngeneic mouse model and leads to increased intratumoral infiltration of DCs, NK cells, and CD107a⁺CD8⁺ T cells, but not T cells, PD-1⁺CD8⁺ T cells, TIM-3⁺CD8⁺ Infiltration of T cells and LAG3⁺CD8⁺ T cells was reduced.

HPK1-IN-3 is a potent and selective ATP-competitive hematopoietic progenitor kinase 1 (HPK1; MAP4K1) inhibitor with an IC₅₀ of 0.25 nM. HPK1-IN-3 has IL-2 cellular potency with an EC₅₀ of 108 nM in human peripheral blood mononuclear cells (PBMCs).

HPK1-IN-32 is a potent and selective HPK1 inhibitor with an IC₅₀ of 65 nM. HPK1-IN-32 can be used for the research of HPK1 related disorders or diseases.

HPK1-IN-7 is a potent, orally active HPK1 (hematopoietic progenitor kinase 1, MAP4K1) inhibitor (IC₅₀=2.6 nM) with excellent family and kinome selectivity. HPK1-IN-7 shows selectivity against IRAK4 (59 nM) and GLK (140 nM). HPK1-IN-7 shows robust efficacy against MC38 syngeneic tumor model in combination with anti-PD1.

HPK1-IN-68 (Compound 39) is a HPK1 inhibitor with an IC₅₀ of 2.8 nM. HPK1-IN-68 blocks HPK1 signaling, inhibits HPK1-mediated phosphorylation of SLP76, and promotes the production of the IL-2 cytokine. HPK1-IN-68 antagonizes the immunosuppressive effect mediated by PGE2. HPK1-IN-68 enhances the infiltration of CD3⁺/CD8⁺ T cells into tumor tissues. HPK1-IN-68 exerts T cell-dependent antitumor efficacy in a mouse colon cancer model. HPK1-IN-68 exhibits significant synergistic antitumor effects when used in combination with anti-PD-1. HPK1-IN-68 is applicable to research related to colon cancer.

HDM2004 is a selective, orally active, blood-brain barrier-penetrant HPK1 inhibitor with an IC₅₀ of 1.89 nM. HDM2004 exhibits anticancer activity against colon cancer. HDM2004 shows synergistic activity when combined with anti-PD-L1 in syngeneic mouse models. HDM2004 can be used for the research of colon cancer.

HPK1/GLK-IN-1 is a HPK1 and GLK inhibitor. HPK1/GLK-IN-1 (compound 38) potently inhibits GLK with an IC₅₀ of  33 nM. HPK1-IN-26 can be used for the research of animal pathogen infection.

HPK1-IN-34 (Compound 143) is a Hematopoietic progenitor kinase 1 (HPK1) inhibitor with an IC₅₀ of <100 nM. HPK1-IN-34 is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.

GNE-6893 is an orally active, selective HPK1 inhibitor with a K_i < 0.02 nM. GNE-6893 enhances T cell receptor signaling in primary human T cells. GNE-6893 increases IL2 production in stimulated primary human T cells. GNE-6893 can be used for the research of chronic refractory cancers.

SS47 TFA, a PROTAC-based HPK1 degrader, exerts proteasome-mediated HPK1 degradation. The degradation of HPK1 via SS47 also significantly enhances the in vivo antitumor efficacy of BCMA CAR-T cell research. HPK1, an immunosuppressive regulatory kinase, is a promising target for cancer immunotherapies. SS47 (TFA) is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.

NDI-101150 is an orally active, potent and selective hematopoietic progenitor cell kinase 1 (HPK1) inhibitor with an IC₅₀ of 0.7 nM. NDI-101150 blocks HPK1-mediated negative regulation of immune receptor signaling, inhibits immunosuppression of T cell activation, enhances antigen-specific antibody production and augments B-cell activation. NDI-101150 inhibits tumor growth in syngeneic tumor models, establishes durable antitumor immune memory, and synergizes with anti-PD1 to enhance exhausted T cell activity and drive tumor regressions. NDI-101150 can be used for the research of cancer, such as breast cancer and colon cancer.

KHK-6 is an inhibitor for serine/threonine kinase hematopoietic progenitor kinase 1 (HPK 1) with an IC₅₀ of 20 nM. KHK-6 enhances CD3/CD28-induced cytokine production, enhances CD69, CD25 and HLA-DR markers on CD4+ and CD8+ T cells, and enhances T cell-mediated killing activity of SKOV3 and A549 cells.

HPK1-IN-62 is a selective and orally active HPK-1 inhibitor with an IC₅₀ of 1.22 nM. HPK1-IN-62 significantly improves GLK selectivity (> 665-fold) and LCK selectivity (> 1095-fold). HPK1-IN-62 enhances T-cell activation and demonstrated synergistic effects when combined with anti-mPD-1 therapy in the MC38 tumor model, inhibiting a tumor growth. HPK1-IN-62 can be used in the researchs of colon cancer and cancer immunotherapy.

HPK1-IN-21 is a potent inhibitor of HPK1 kinase inhibitor (Ki=0.8 nM). HPK1-IN-21 also has orally active.

HPK1-IN-56 (Compound A29) is a HPK1 inhibitor (IC₅₀: 2.70 nM). HPK1-IN-56 inhibits downstream p-SLP76 (IC₅₀: 8.1 nM in Jurkat T cells). HPK1-IN-56 induces the production of IL-2 in human PBMCs. HPK1-IN-56 has anticancer effect, enhances T-cell killing ability and the antitumor efficacy of anti-PD-1 antibody.

HPK1-IN-36 (compound 2) is a potent HPK1 inhibitor with an IC₅₀ value of 0.5 nM.

HPK1-IN-64 is a potent, selective, and orally active HPK1 inhibitor with an IC₅₀ value of 1.9 nM. HPK1-IN-64 exhibits selectivity exceeding 100-fold, 80-fold, 300-fold, and 350-fold against off-target kinases such as GLK, MAP4K5, TBK1, and TNIK, respectively. HPK1-IN-64 inhibits SLP76 protein phosphorylation and IL-2 secretion. HPK1-IN-64 may be used in cancer research, such as for colorectal cancer.

HPK1-IN-67, a HPK1 inhibitor, is a ligand for target protein for PROTAC. HPK1-IN-67 can be used for synthesis of PROTACs, such as PROTAC HPK1 Degrader-7 (HY-179727).

HPK1-IN-44 (Compound 1) is an inhibitor of HPK1 (IC₅₀=0.1 nM (40 μM ATP)).