MAP4K Inhibitor

Rentosertib (INS018 055) (compound 112) is the orally active TNIK and MAP4K4 inhibitor with IC₅₀ values of 12-120, 12-120 nM, respectively.

GNE-495 is a potent and selective MAP4K4 inhibitor with an IC₅₀ of 3.7 nM.

NCB-0846 is an orally active, selective inhibitor for Wnt, that inhibits Traf2- and Nck-interacting kinase (TNIK) with an IC₅₀ of 21 nM. NCB-0846 blocks TGF-β signaling pathway by inhibiting SMAD2/3 phosphorylation and nuclear translocation.

NG25 is a potent dual TAK1 and MAP4K2 inhibitor, with IC₅₀s of 149 nM and 21.7 nM, respectively.

PF-06260933 is an orally active and highly selective inhibitor of MAP4K4 with IC₅₀s of 3.7 and 160 nM for kinase and cell, respectively.

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.

DMX-5804 is a potent, orally active and selective MAP4K4 inhibitor, with an IC₅₀ of 3 nM, a pIC₅₀ of 8.55 for human MAP4K4, less potent on MINK1/MAP4K6 (pIC₅₀, 8.18), and TNIK/MAP4K7 (pIC₅₀, 7.96). DMX-5804 enhances cardiomyocyte survival, and reduces ischemia-reperfusion injury in mice.

KY-05009 is an ATP-competitive Traf2- and Nck-interacting kinase (TNIK) inhibitor with a K_i of 100 nM. KY-05009 pharmacologically inhibits TGF-β1-induced epithelial-to-mesenchymal transition (EMT) in human lung adenocarcinoma cells. KY-05009 inhibits the protein expression of TNIK and transcriptional activity of Wnt target genes and induces apoptosis in cancer cells. KY-05009 exerts anti-cancer activity.

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

Famlasertib is a potent, brain-penetrant MAP4K inhibitor with IC₅₀s value of 0.3 nM, 23.7 nM, and 44.7 nM for HGK (MAP4K4), MLK3, and MLK1, respectively. Famlasertib shows motor neuron protection and anti-inflammatory properties. Famlasertib can be used for the study of amyotrophic lateral sclerosis (ALS).

Octahydrocurcumin (Hexahydrobisdemethoxycurcumin) is an orally active anticancer and anti-inflammatory agent, and is the final hydrogenated metabolite of Curcumin (HY-N0005) in vivo. Octahydrocurcumin exerts its anti-tumor and anti-inflammatory effects by inducing the mitochondrial apoptosis pathway and inhibiting the TAK1-NF-κB-COX-2 pathway, respectively.

FMF-06-098-1 is a multi-target kinase PROTAC degrader. FMF-06-098-1 can be used to target degradation kinases which degrades AAK1, AΒL2, AURKA, AURKB, BUBIB, CDC7, CDK1, CDK12, CDK13, CDK2, CDK4, CDk6, CDK7, CDK9, CHEK1, CSNKID, EPHA1, PER, FGFR1, GAK, IRAK4, ITK, LIMK2, MAP4K2, MAP4K3, MAPK6, MAPK7, MARK4, MELK, PKN3, PLK4, PRKAA1, PTK2, PTK6, RPS6KA4, S1K2, STK35, TNK2, UHMK1, ULK1, and WEE1.

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.

MAP4K4-IN-3 (Compound 17) is a potent and selective MAP4K4 inhibitor with an IC₅₀ of 14.9 nM in kinase assay, an IC₅₀ of 470 nM in cell assay. Antidiabetic agent.

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).

TAK1/MAP4K2 inhibitor 1 is a potent dual TGFβ-activated kinase 1 (TAK1) and mitogen-activated protein kinase kinase kinase kinase 2 (MAP4K2) inhibitor, with IC₅₀s of 41.1 nM and 18.2 nM, respectively.

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.

TL4-12 is a selective MAP4K2/GCK inhibitor, dose-dependently downregulates IKZF1 and BCL-6 and leads to MM cell proliferation inhibition (IC₅₀=37 nM) accompanied by induction of apoptosis. TL4-12 can be used to overcome immunomodulatory agent resistance in multiple myeloma (MM).