MAP4K4/HGK 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.

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.

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.

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).

F1386-0303 is a highly selective MAP4K4 inhibitor with an IC₅₀ of 34 nM against human targets. F1386-0303 exerts cardiomyocyte protective and function-preserving effects through mechanisms such as alleviating oxidative stress, inhibiting caspases, and maintaining mitochondrial membrane potential, while it does not interfere with the activity of Doxorubicin (HY-15142A) in cancer cells. F1386-0303 is rapidly cleared and has no bioavailability in mice, but it is well-suited as a tool compound for target validation. F1386-0303 can be applied to studies related to cardiac ischemia-reperfusion injury, Doxorubicin-induced cardiotoxicity, myocardial infarction and other related conditions.

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.

Pyrrolo[2,1-f][1,2,4]triazin-4-amine is a MAP4K4 inhibitor with a surface plasmon resonance (SPR) K_d of 88 μM and a ligand efficiency of 0.56.

GNE 220 (hydrochloride) is a potent and selective inhibitor of MAP4K4, with an IC₅₀ of 7 nM.

GNE-220 is a potent and selective inhibitor of MAP4K4 with an IC₅₀ of 7 nM.

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.

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.

RET-IN-19 (compound 59) is a potent RET inhibitor, with IC₅₀ values of 6.8 and 13.51 nM against RET-wt and RET V804M, respectively. RET-IN-19 shows anticancer activity. RET-IN-19 can be used for non-small cell lung cancer (NSCLC) research.

FLT3/ITD-IN-4 (Compound 16) is a selective FMS-like tyrosine kinase 3 internal tandem duplications (FLT3-ITD) inhibitor with an IC₅₀ of 2.3 nM. FLT3/ITD-IN-4 can be used for acute myeloid leukemia research.

HPK1-IN-52 is a potent and orally active hematopoietic progenitor kinase 1 (HPK1) inhibitor with an IC₅₀ value of 10.4 nM. HPK1-IN-52 exhibits anti-tumor activities.

PI4K-IN-3 (Compound 27) is an orally active PI4K inhibitor with an IC₅₀ of 1.9  nM for Plasmodium vivax PI4K. PI4K-IN-3 has no hERG channel inhibition and mammalian cytotoxicity. PI4K-IN-3 has significant selectivity against the human MINK1 and MAP4K4 kinases but with low selectivity against human PI3Kα and PI4Kβ. PI4K-IN-3 has potent antimalarial activity and significantly reduces parasitaemia in NSG mice mouse models of Plasmodium falciparum malaria.