MAP4K Inhibitor

HPK1-IN-17 is a potent and selective inhibitor of HPK1. Hematopoietic progenitor kinase 1 (HPKl) originally cloned from hematopoietic progenitor cells is a member of MAP kinase kinase kinase kinases (MAP4Ks) family. HPK1-IN-17 is useful in researching, preventing or ameliorating diseases or disorders associated with HPK1 activity such as cancer (extracted from patent WO2019238067A1, compound 73).

HPK1-IN-14 is potent inhibitor of HPK1. HPK1 is a serine/threonine protein kinase cloned from hematopoietic progenitor cells and belongs to the MAP4K family of mammalian Ste-20-related protein kinases. HPK1-IN-14 has the potential for the research of HPK1 related diseases (extracted from patent WO2021213317A1, compound 79) .

HPK1-IN-11 is potent inhibitor of HPK1. HPK1 is a serine/threonine protein kinase cloned from hematopoietic progenitor cells and belongs to the MAP4K family of mammalian Ste-20-related protein kinases. HPK1-IN-11 has the potential for the research of HPK1 related diseases (extracted from patent WO2021213317A1, compound 2).

HPK1-IN-10 is potent inhibitor of HPK1. HPK1 is a serine/threonine protein kinase cloned from hematopoietic progenitor cells and belongs to the MAP4K family of mammalian Ste-20-related protein kinases. HPK1-IN-10 has the potential for the research of HPK1 related diseases (extracted from patent WO2021213317A1, compound 103) .

NG25 trihydrochloride is a dual TAK1 and MAP4K2 inhibitor (IC₅₀: 149 nM and 21.7 nM respectively). NG25 sensitizes the breast cancer cells to Doxorubicin (HY-15142A), and enhances apoptosis. NG25 trihydrochloride can be used for research of various cancers.

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.

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.

MAP4K4-IN-7 (Compound 8) is a MAP4K4 inhibitor. MAP4K4-IN-7 shows moderate inhibitory activity against TNIK, MAP4K4, and MINK1 with pIC₅₀ values of 6.8, 6.8, and 6.7 respectively. MAP4K4-IN-7 can be used for the researches of cancer and neurological disease, such as schizophrenia.

CA/PRAK-IN-1 is a dual inhibitor of carbonic anhydrase (Carbonic Anhydrase) and PRAK, with a K_i of 20.1 nM against hCA IX and 16.4 nM against hCA XII. CA/PRAK-IN-1 exhibits inhibitory activity against YES1 kinase, BTK, and MAP4K3. CA/PRAK-IN-1 induces G0/G1 phase arrest of the cancer cell cycle, inhibits DNA synthesis, disrupts hypoxia-driven survival pathways, promotes cell death, and shows broad-spectrum cytotoxicity against tumor cells. CA/PRAK-IN-1 can be used in research on various cancers including leukemia, colon cancer, melanoma, and renal cancer.

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-57 (Compound 10c) is a hematopoietic progenitor kinase 1 (HPK1) inhibitor with an IC₅₀ value of 0.09 nM. HPK1-IN-57 inhibits the activity of HPK1 kinase, hindering the phosphorylation of the downstream adaptor protein SLP76 (IC₅₀ is 33.74 nM) and effectively stimulating the secretion of the T cell activation marker IL-2 (EC₅₀ is 84.24 nM). HPK1-IN-57 is promising for research of tumor immunotherapy.

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

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-IN-39 (Compound 10n) is a selective HPK1 Inhibitor (IC₅₀: 29 nM). HPK1-IN-39 inhibits the phosphorylation of SLP76. HPK1-IN-39 can be used for research of cancer immunotherapy.

PF-06745013 (Compound 37) is a MAP4K4 inhibitor without time-dependent inhibition (TDI) risk of CYP3A4 (IC₅₀ of 0.4  nM for MAP4K4). PF-06745013 has no accumulation CNS-impaired and non-ATP competitive activities in mouse models. PF-06745013 can be used for inflammatory diseases like diabetes and cancers research.

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.

HMC-B17 is a selective, orally bioavailable HPK1 inhibitor (IC₅₀ = 1.39 nM) that potentiates anti-PD-L1 efficacy. HMC-B17 potently enhances the IL-2 secretion in Jurkat cells (EC₅₀ = 11.56 nM). HMC-B17 can be used for the research of cancer.

HPK1-IN-58 (Compound 26) is an inhibitor of HPK1 (IC₅₀: 2.6 nM) and SLP76 (IC₅₀: 20 nM). HPK1-IN-58 enhances IL-2 secretion and reverses PGE2-induced immunosuppression. HPK1-IN-58 can be used in anti-tumor immunity research.

HPK1-IN-61 (Compound 1) is an inhibitor of hematopoietic progenitor kinase 1 (HPK1) (K_i = 0.4 nM) and an inhibitor of Abl (IC₅₀ < 0.51 nM). HPK1-IN-61 also shows inhibitory activity against LCK with an IC₅₀ of 24 nM.

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