MAP4K6/MINK1
MAP4K6/MINK1 is a germinal-center-kinase family serine/threonine kinase that regulates cytoskeletal organization, oncogene-induced cell senescence, and cytokinesis completion[1]. Mechanistically, MINK1 acts within the STRIPAK network, directly interacts with STRN4, and is required for abscission after cleavage-furrow formation[1]. In the Hippo pathway, MAP4K6/MINK1 belongs to the Misshapen homologues MAP4K4/6/7, which directly activate LATS1/2 and regulate YAP/TAZ in parallel with MST1/2[2]. This distinguishes MAP4K6/MINK1 from MST isoforms because combined deletion of MAP4Ks and MST1/2, but neither alone, suppresses LATS1/2 and YAP/TAZ phosphorylation across multiple upstream signals[2]. In immune models, MINK1 negatively regulates Th17 differentiation by phosphorylating SMAD2 T324, thereby limiting SMAD2 activation and autoimmune inflammation[3]. In cancer models, CRISPR kinome screening identified MINK1 as a driver of 5-FU resistance in oral squamous cell carcinoma through the AKT/MDM2/p53 axis, and lestaurtinib inhibited MINK1 kinase activity in resistant cells[4].
Références:
- [1]. Hyodo T, et al. Misshapen-like kinase 1 (MINK1) is a novel component of striatin-interacting phosphatase and kinase (STRIPAK) and is required for the completion of cytokinesis. J Biol Chem. 2012 Jul 20;287(30):25019-29. [Content Brief]
- [2]. Meng Z, et al. MAP4K family kinases act in parallel to MST1/2 to activate LATS1/2 in the Hippo pathway. Nat Commun. 2015 Oct 5;6:8357. [Content Brief]
- [3]. Fu G, et al. Suppression of Th17 cell differentiation by misshapen/NIK-related kinase MINK1. J Exp Med. 2017 May 1;214(5):1453-1469. [Content Brief]
- [4]. Mohanty S, et al. CRISPR-based kinome-screening revealed MINK1 as a druggable player to rewire 5FU-resistance in OSCC through AKT/MDM2/p53 axis. Oncogene. 2022 Nov;41(45):4929-4940. [Content Brief]
All Product Categories
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MAP4K6/MINK1 Produits associés (7)
Produits associés (7)
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DMX-5804
0 ImagesDMX-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.
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GNE 220 hydrochloride
0 ImagesGNE 220 (hydrochloride) is a potent and selective inhibitor of MAP4K4, with an IC50 of 7 nM.
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GNE 220
0 ImagesCat. No.: HY-U00428CAS No.: 1199590-75-4GNE-220 is a potent and selective inhibitor of MAP4K4 with an IC50 of 7 nM.
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MAP4K4-IN-7
0 ImagesCat. No.: HY-W402208CAS No.: 1499162-60-5MAP4K4-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.
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HPK1-IN-56
0 ImagesCat. No.: HY-172107CAS No.: 2901054-39-3HPK1-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.
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HPK1-IN-52
0 ImagesCat. No.: HY-168110CAS No.: 2994298-66-5HPK1-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.
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PI4K-IN-3
0 ImagesCat. No.: HY-178775PI4K-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.
