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large tumor suppressor kinase 1

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Target id: 1515

Nomenclature: large tumor suppressor kinase 1

Abbreviated Name: LATS1

Family: NDR family

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 1130 6q25.1 LATS1 large tumor suppressor kinase 1
Mouse - 1129 10 A1 Lats1 large tumor suppressor
Rat - 1130 1p13 Lats1 large tumor suppressor kinase 1
Previous and Unofficial Names Click here for help
Large tumor suppressor homologue 1 | WARTS
Database Links Click here for help
Alphafold O95835 (Hs), Q8BYR2 (Mm)
BRENDA 2.7.11.1
ChEMBL Target CHEMBL6167 (Hs)
Ensembl Gene ENSG00000131023 (Hs), ENSMUSG00000040021 (Mm), ENSRNOG00000014916 (Rn)
Entrez Gene 9113 (Hs), 16798 (Mm), 308265 (Rn)
Human Protein Atlas ENSG00000131023 (Hs)
KEGG Enzyme 2.7.11.1
KEGG Gene hsa:9113 (Hs), mmu:16798 (Mm), rno:308265 (Rn)
OMIM 603473 (Hs)
Pharos O95835 (Hs)
RefSeq Nucleotide NM_001270519 (Hs), NM_010690 (Mm), NM_001134543 (Rn)
RefSeq Protein NP_004681 (Hs), NP_034820 (Mm), NP_001128015 (Rn)
UniProtKB O95835 (Hs), Q8BYR2 (Mm)
Wikipedia LATS1 (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
lestaurtinib Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 7.5 pKd 7
⤷ pKd 7.5 (Kd 3x10-8 M) [7]
staurosporine Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.4 pKd 2
⤷ pKd 7.4 (Kd 4.2x10-8 M) [2]
K-252a Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.2 pKd 4
⤷ pKd 7.2 (Kd 6.76x10-8 M) [4]
PF-3758309 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.8 pKd 4
⤷ pKd 6.8 (Kd 1.585x10-7 M) [4]
AST-487 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.3 pKd 2
⤷ pKd 6.3 (Kd 4.7x10-7 M) [2]
sunitinib Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.2 pKd
⤷ pKd 6.2 (Kd 6.3x10-7 M)
BI-847325 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.2 pKd 4
⤷ pKd 6.2 (Kd 6.3x10-7 M) [4]
A-674563 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.0 pKd 2
⤷ pKd 6.0 (Kd 1.1x10-6 M) [2]
midostaurin Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 6.0 pKd 7
⤷ pKd 6.0 (Kd 1.1x10-6 M) [7]
defactinib Small molecule or natural product Ligand has a PDB structure Hs Inhibition 5.0 pKd 4
⤷ pKd 5.0 (Kd 9.12x10-6 M) [4]
nintedanib Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 5.0 pKd 4
⤷ pKd 5.0 (Kd 1.071x10-5 M) [4]
TRULI Small molecule or natural product Click here for species-specific activity table Hs Inhibition 9.7 pIC50 3
⤷ pIC50 9.7 (IC50 2x10-10 M) [3]
Description: LATS1 inhibition at 10 μM ATP
example 320 [WO2018198077A2] Small molecule or natural product Hs Inhibition 9.1 pIC50 1
⤷ pIC50 9.1 (IC50 7x10-10 M) [1]
Description: Inhibition of human LATS1 kinase domain determined in a biochemical fluorescence-based assay
staurosporine Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.9 pIC50 5
⤷ pIC50 7.9 (IC50 1.28x10-8 M) [5]
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: 2,6
Key to terms and symbols Click column headers to sort
Target used in screen: LATS1
Ligand Sp. Type Action Value Parameter
lestaurtinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.5 pKd
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.4 pKd
AST-487 Small molecule or natural product Hs Inhibitor Inhibition 6.3 pKd
sunitinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 6.2 pKd
SU-14813 Small molecule or natural product Hs Inhibitor Inhibition 6.1 pKd
midostaurin Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.0 pKd
A-674563 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.0 pKd
NVP-TAE684 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 5.8 pKd
dovitinib Small molecule or natural product Hs Inhibitor Inhibition 5.8 pKd
linifanib Small molecule or natural product Hs Inhibitor Inhibition 5.7 pKd
Displaying the top 10 most potent ligands  View all ligands in screen »
Immunopharmacology Comments
LATS1 and LATS2 are included in the GToImmuPdb because of their crucial role in Hipo signalling, a major mammalian signalling cascade that has recently been identified as playing an important role in shaping the innate immune response [1-2,4].
General Comments
This Ser/Thr kinase is a member of the large tumor suppressor (LATS) family. It participates in the Hippo signalling pathway that regulates organ development, growth and regeneration, and some aspects of cell contact. Dysregulated expression and/or function of LATS1 has been detected in some cancers.

References

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1. Behnke D, Berenshteyn F, Hao X, Hoffman T, Jin Q, Lacoste A, Lee C, Liu J, Liu Y, Maibaum JK et al.. (2018) 6-6 fused bicyclic heteroaryl compounds and their use as lats inhibitors. Patent number: WO2018198077A2. Assignee: Novartis Ag. Priority date: 26/04/2018. Publication date: 01/11/2018.

2. 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]

3. Kastan N, Gnedeva K, Alisch T, Petelski AA, Huggins DJ, Chiaravalli J, Aharanov A, Shakked A, Tzahor E, Nagiel A et al.. (2021) Small-molecule inhibition of Lats kinases may promote Yap-dependent proliferation in postmitotic mammalian tissues. Nat Commun, 12 (1): 3100. [PMID:34035288]

4. Klaeger S, Heinzlmeir S, Wilhelm M, Polzer H, Vick B, Koenig PA, Reinecke M, Ruprecht B, Petzoldt S, Meng C et al.. (2017) The target landscape of clinical kinase drugs. Science, 358 (6367). [PMID:29191878]

5. Narayan S, Ramisetti S, Jaiswal AS, Law BK, Singh-Pillay A, Singh P, Amin S, Sharma AK. (2019) ASR352, A potent anticancer agent: Synthesis, preliminary SAR, and biological activities against colorectal cancer bulk, 5-fluorouracil/oxaliplatin resistant and stem cells. Eur J Med Chem, 161: 456-467. [PMID:30384048]

6. 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]

7. Zarrinkar PP, Gunawardane RN, Cramer MD, Gardner MF, Brigham D, Belli B, Karaman MW, Pratz KW, Pallares G, Chao Q et al.. (2009) AC220 is a uniquely potent and selective inhibitor of FLT3 for the treatment of acute myeloid leukemia (AML). Blood, 114 (14): 2984-92. [PMID:19654408]

How to cite this page

NDR family: large tumor suppressor kinase 1. Last modified on 09/05/2023. Accessed on 11/10/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=1515.