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misshapen like kinase 1

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Immunopharmacology Ligand target has curated data in GtoImmuPdb

Target id: 2103

Nomenclature: misshapen like kinase 1

Abbreviated Name: MINK

Family: MSN subfamily

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 1332 17p13.2 MINK1 misshapen like kinase 1
Mouse - 1308 11 B3 Mink1 misshapen-like kinase 1 (zebrafish)
Rat - 1336 10q24 Mink1 misshapen-like kinase 1
Previous and Unofficial Names Click here for help
GCK family kinase MiNK | MAP4K6 | MAPK/ERK kinase kinase kinase 6 | MEK kinase kinase 6 | MEKKK 6 | MINK | YSK2 | ZC3
Database Links Click here for help
Alphafold Q8N4C8 (Hs), Q9JM52 (Mm), F1LP90 (Rn)
BRENDA 2.7.11.1
CATH/Gene3D 1.25.10.10
ChEMBL Target CHEMBL5518 (Hs)
Ensembl Gene ENSG00000141503 (Hs), ENSMUSG00000020827 (Mm), ENSRNOG00000033508 (Rn)
Entrez Gene 50488 (Hs), 50932 (Mm), 303259 (Rn)
Human Protein Atlas ENSG00000141503 (Hs)
KEGG Enzyme 2.7.11.1
KEGG Gene hsa:50488 (Hs), mmu:50932 (Mm), rno:303259 (Rn)
OMIM 609426 (Hs)
Pharos Q8N4C8 (Hs)
RefSeq Nucleotide NM_001024937 (Hs), NM_001045959 (Mm), NM_001271136 (Rn)
RefSeq Protein NP_001020108 (Hs), NP_001039424 (Mm), NP_001258065 (Rn)
UniProtKB Q8N4C8 (Hs), Q9JM52 (Mm), F1LP90 (Rn)
Wikipedia MINK1 (Hs)
Enzyme Reaction Click here for help
EC Number: 2.7.11.1

Download all structure-activity data for this target as a CSV file go icon to follow link

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
PF-03715455 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 8.2 pIC50 10
⤷ pIC50 8.2 (IC50 6x10-9 M) [10]
PF06260933 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.1 pIC50 1
⤷ pIC50 8.1 (IC50 8x10-9 M) [1]
pexmetinib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.6 pIC50 3
⤷ pIC50 7.6 (IC50 2.6x10-8 M) [3]
DiscoveRx KINOMEscan® screen Click here for help
A screen of 72 inhibitors against 456 human kinases. Quantitative data were derived using DiscoveRx KINOMEscan® platform.
http://www.discoverx.com/services/drug-discovery-development-services/kinase-profiling/kinomescan
Reference: 5,11
Key to terms and symbols Click column headers to sort
Target used in screen: MINK
Ligand Sp. Type Action Value Parameter
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 9.0 pKd
bosutinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 8.5 pKd
lestaurtinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 8.4 pKd
AST-487 Small molecule or natural product Hs Inhibitor Inhibition 8.1 pKd
dovitinib Small molecule or natural product Hs Inhibitor Inhibition 8.0 pKd
KW-2449 Small molecule or natural product Hs Inhibitor Inhibition 7.6 pKd
neratinib Small molecule or natural product Approved drug Hs Inhibitor Inhibition 7.5 pKd
sunitinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 7.5 pKd
SU-14813 Small molecule or natural product Hs Inhibitor Inhibition 7.2 pKd
JNJ-28312141 Small molecule or natural product Hs Inhibitor Inhibition 7.1 pKd
Displaying the top 10 most potent ligands  View all ligands in screen »
EMD Millipore KinaseProfilerTM screen/Reaction Biology Kinase HotspotSM screen Click here for help
A screen profiling 158 kinase inhibitors (Calbiochem Protein Kinase Inhibitor Library I and II, catalogue numbers 539744 and 539745) for their inhibitory activity at 1µM and 10µM against 234 human recombinant kinases using the EMD Millipore KinaseProfilerTM service.

A screen profiling the inhibitory activity of 178 commercially available kinase inhibitors at 0.5µM against a panel of 300 recombinant protein kinases using the Reaction Biology Corporation Kinase HotspotSM platform.

http://www.millipore.com/techpublications/tech1/pf3036
http://www.reactionbiology.com/webapps/main/pages/kinase.aspx

Reference: 2,6
Key to terms and symbols Click column headers to sort
Target used in screen: MINK/MINK(MINK1)
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
K-252a Small molecule or natural product Hs Inhibitor Inhibition 0.4 0.0 1.0
SB 218078 Small molecule or natural product Hs Inhibitor Inhibition 0.9 86.0 71.0
bosutinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 1.2
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 1.6 0.5 0.5
dovitinib Small molecule or natural product Hs Inhibitor Inhibition 1.6
JAK3 inhibitor VI Small molecule or natural product Hs Inhibitor Inhibition 1.7 6.0 1.0
Gö 6976 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 2.5 21.0 16.0
Cdk1/2 inhibitor III Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 3.1 18.0 2.0
SU11652 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 4.4 9.0 2.0
Flt-3 inhibitor II Small molecule or natural product Hs Inhibitor Inhibition 9.9 21.0 4.0
Displaying the top 10 most potent ligands  View all ligands in screen »
Immunopharmacology Comments
MINK promotes the negative selection of autoreactive thymocytes during T cell development, an action that is effected by JNK-mediated apoptosis [9].
Immuno Process Associations
Immuno Process:  Cellular signalling
Immuno Process:  Immune system development
Immuno Process:  T cell (activation)
General Comments
MINK (MINK1, also known as MAP4K6) is ubiquitously expressed in mice and humans, and is found in most tissues [4,7]. Exogenously expressed MINK activates the JNK pathway and p38 signalling in vitro, and studies in cell lines indicate roles for MINK in the regulation of cytoskeletal reorganisation, cell adhesion, and cell motility (NCK(TNIK)-dependent activities), and neuronal structure and function (via activation of Rap2 (RAP2A), a Ras family GTPase) [8].

References

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1. Ammirati M, Bagley SW, Bhattacharya SK, Buckbinder L, Carlo AA, Conrad R, Cortes C, Dow RL, Dowling MS, El-Kattan A et al.. (2015) Discovery of an in Vivo Tool to Establish Proof-of-Concept for MAP4K4-Based Antidiabetic Treatment. ACS Med Chem Lett, 6 (11): 1128-33. [PMID:26617966]

2. Anastassiadis T, Deacon SW, Devarajan K, Ma H, Peterson JR. (2011) Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity. Nat Biotechnol, 29 (11): 1039-45. [PMID:22037377]

3. Bachegowda L, Morrone K, Winski SL, Mantzaris I, Bartenstein M, Ramachandra N, Giricz O, Sukrithan V, Nwankwo G, Shahnaz S et al.. (2016) Pexmetinib: A Novel Dual Inhibitor of Tie2 and p38 MAPK with Efficacy in Preclinical Models of Myelodysplastic Syndromes and Acute Myeloid Leukemia. Cancer Res, 76 (16): 4841-4849. [PMID:27287719]

4. Dan I, Watanabe NM, Kobayashi T, Yamashita-Suzuki K, Fukagaya Y, Kajikawa E, Kimura WK, Nakashima TM, Matsumoto K, Ninomiya-Tsuji J et al.. (2000) Molecular cloning of MINK, a novel member of mammalian GCK family kinases, which is up-regulated during postnatal mouse cerebral development. FEBS Lett, 469 (1): 19-23. [PMID:10708748]

5. Davis MI, Hunt JP, Herrgard S, Ciceri P, Wodicka LM, Pallares G, Hocker M, Treiber DK, Zarrinkar PP. (2011) Comprehensive analysis of kinase inhibitor selectivity. Nat Biotechnol, 29 (11): 1046-51. [PMID:22037378]

6. Gao Y, Davies SP, Augustin M, Woodward A, Patel UA, Kovelman R, Harvey KJ. (2013) A broad activity screen in support of a chemogenomic map for kinase signalling research and drug discovery. Biochem J, 451 (2): 313-28. [PMID:23398362]

7. Hu Y, Leo C, Yu S, Huang BC, Wang H, Shen M, Luo Y, Daniel-Issakani S, Payan DG, Xu X. (2004) Identification and functional characterization of a novel human misshapen/Nck interacting kinase-related kinase, hMINK beta. J Biol Chem, 279 (52): 54387-97. [PMID:15469942]

8. Hussain NK, Hsin H, Huganir RL, Sheng M. (2010) MINK and TNIK differentially act on Rap2-mediated signal transduction to regulate neuronal structure and AMPA receptor function. J Neurosci, 30 (44): 14786-94. [PMID:21048137]

9. McCarty N, Paust S, Ikizawa K, Dan I, Li X, Cantor H. (2005) Signaling by the kinase MINK is essential in the negative selection of autoreactive thymocytes. Nat Immunol, 6 (1): 65-72. [PMID:15608642]

10. Millan DS, Bunnage ME, Burrows JL, Butcher KJ, Dodd PG, Evans TJ, Fairman DA, Hughes SJ, Kilty IC, Lemaitre A et al.. (2011) Design and synthesis of inhaled p38 inhibitors for the treatment of chronic obstructive pulmonary disease. J Med Chem, 54 (22): 7797-814. [PMID:21888439]

11. Wodicka LM, Ciceri P, Davis MI, Hunt JP, Floyd M, Salerno S, Hua XH, Ford JM, Armstrong RC, Zarrinkar PP et al.. (2010) Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry. Chem Biol, 17 (11): 1241-9. [PMID:21095574]

How to cite this page

MSN subfamily: misshapen like kinase 1. Last modified on 19/03/2024. Accessed on 19/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2103.