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large tumor suppressor kinase 2

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Immunopharmacology Ligand  Target has curated data in GtoImmuPdb

Target id: 1516

Nomenclature: large tumor suppressor kinase 2

Abbreviated Name: LATS2

Family: NDR family

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 1088 13q12.11 LATS2 large tumor suppressor kinase 2
Mouse - 1042 14 C3 Lats2 large tumor suppressor 2
Rat - 1042 15p12 Lats2 large tumor suppressor kinase 2
Previous and Unofficial Names Click here for help
KPM | Large tumor suppressor homologue 2 | large tumor suppressor 2
Database Links Click here for help
Alphafold Q9NRM7 (Hs), Q7TSJ6 (Mm)
BRENDA 2.7.11.1
ChEMBL Target CHEMBL5907 (Hs)
Ensembl Gene ENSG00000150457 (Hs), ENSMUSG00000021959 (Mm), ENSRNOG00000056343 (Rn)
Entrez Gene 26524 (Hs), 50523 (Mm), 305922 (Rn)
Human Protein Atlas ENSG00000150457 (Hs)
KEGG Enzyme 2.7.11.1
KEGG Gene hsa:26524 (Hs), mmu:50523 (Mm), rno:305922 (Rn)
OMIM 604861 (Hs)
Pharos Q9NRM7 (Hs)
RefSeq Nucleotide NM_014572 (Hs), NM_015771 (Mm), NM_001107267 (Rn)
RefSeq Protein NP_055387 (Hs), NP_056586 (Mm), NP_700431 (Mm), NP_001100737 (Rn)
UniProtKB Q9NRM7 (Hs), Q7TSJ6 (Mm)
Wikipedia LATS2 (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Solution structure of RSGI RUH-038, a UBA domain from Mouse LATS2 (Large Tumor Suppressor homolog 2)
PDB Id:  2COS
Resolution:  0.0Å
Species:  Mouse
References: 
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 9.0 pKd 6
⤷ pKd 9.0 (Kd 1x10-9 M) [6]
staurosporine Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.8 pKd 1
⤷ pKd 7.8 (Kd 1.7x10-8 M) [1]
GSK690693 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.8 pKd 1
⤷ pKd 6.8 (Kd 1.4x10-7 M) [1]
sunitinib Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.3 pKd 6
⤷ pKd 6.3 (Kd 4.6x10-7 M) [6]
A-674563 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.2 pKd 1
⤷ pKd 6.2 (Kd 6.2x10-7 M) [1]
midostaurin Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 5.7 pKd 6
⤷ pKd 5.7 (Kd 2.2x10-6 M) [6]
AST-487 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 5.5 pKd 1
⤷ pKd 5.5 (Kd 3x10-6 M) [1]
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: LATS2 inhibition at 10 μM ATP
staurosporine Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.4 pIC50 4
⤷ pIC50 8.4 (IC50 3.76x10-9 M) [4]
compound 35 [PMID: 20684608] Small molecule or natural product Click here for species-specific activity table Hs Inhibition - - 2
⤷ [2]
Description: Measured as % inhibition using 3μM compound.
Inhibitor Comments
3μM compound 35 [PMID 20684608] inhibits LATS2 activity by 75% [2].
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: 1,5
Key to terms and symbols Click column headers to sort
Target used in screen: LATS2
Ligand Sp. Type Action Value Parameter
lestaurtinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 9.0 pKd
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.8 pKd
GSK690693 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.8 pKd
SU-14813 Small molecule or natural product Hs Inhibitor Inhibition 6.4 pKd
sunitinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 6.3 pKd
dovitinib Small molecule or natural product Hs Inhibitor Inhibition 6.3 pKd
A-674563 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.2 pKd
ruboxistaurin Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.2 pKd
KW-2449 Small molecule or natural product Hs Inhibitor Inhibition 5.8 pKd
linifanib Small molecule or natural product Hs Inhibitor Inhibition 5.8 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].

References

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1. 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]

2. Fang X, Yin Y, Chen YT, Yao L, Wang B, Cameron MD, Lin L, Khan S, Ruiz C, Schröter T et al.. (2010) Tetrahydroisoquinoline derivatives as highly selective and potent Rho kinase inhibitors. J Med Chem, 53 (15): 5727-37. [PMID:20684608]

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. 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]

5. 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]

6. 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 2. Last modified on 09/05/2023. Accessed on 19/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=1516.