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doublecortin like kinase 1

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Target id: 2005

Nomenclature: doublecortin like kinase 1

Abbreviated Name: DCAMKL1

Family: DCAMKL family

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 740 13q13.3 DCLK1 doublecortin like kinase 1
Mouse - 756 3 C Dclk1 doublecortin-like kinase 1
Rat - 433 2q26 Dclk1 doublecortin-like kinase 1
Previous and Unofficial Names Click here for help
Click-I | CPG16 | DCDC3A | DCLK | DMPK-like gamma | double cortin and calcium/calmodulin-dependent protein kinase-like 1 | doublecortin and CaM kinase-like 1 | Myotonic dystrophy protein kinase-like gamma
Database Links Click here for help
Alphafold O15075 (Hs), Q9JLM8 (Mm), O08875 (Rn)
BRENDA 2.7.11.1
CATH/Gene3D 3.10.20.230
ChEMBL Target CHEMBL5683 (Hs)
Ensembl Gene ENSG00000133083 (Hs), ENSMUSG00000027797 (Mm), ENSRNOG00000032922 (Rn)
Entrez Gene 9201 (Hs), 13175 (Mm), 83825 (Rn)
Human Protein Atlas ENSG00000133083 (Hs)
KEGG Enzyme 2.7.11.1
KEGG Gene hsa:9201 (Hs), mmu:13175 (Mm), rno:83825 (Rn)
OMIM 604742 (Hs)
Pharos O15075 (Hs)
RefSeq Nucleotide NM_001195415 (Hs), NM_001111051 (Mm), NM_053343 (Rn)
RefSeq Protein NP_004725 (Hs), NP_001104521 (Mm), NP_445795 (Rn)
UniProtKB O15075 (Hs), Q9JLM8 (Mm), O08875 (Rn)
Wikipedia DCLK1 (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  STRUCTURE OF N-TERMINAL DOUBLECORTIN DOMAIN FROM DCLK: WILD TYPE PROTEIN
PDB Id:  1MG4
Resolution:  1.5Å
Species:  Human
References:  3
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
DCLK1-IN-1 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.0 pKd 2
⤷ pKd 7.0 (Kd 1.09x10-7 M) [2]
Description: Determined in an ITC assay.
DCLK1-IN-1 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 6.6 – 8.0 pIC50 2
⤷ pIC50 8.0 (IC50 9.5x10-9 M) [2]
Description: Determined in a KinomeScan binding assay.
pIC50 6.6 (IC50 2.79x10-7 M) [2]
Description: Determined in a NanoBRET cell assay.
compound 5g [PMID: 20483621] Small molecule or natural product Click here for species-specific activity table Hs Inhibition - - 4
⤷ [4]
Description: Measured as % inhibition using 1μM compound.
Inhibitor Comments
1μM compound 5g [PMID 20483621] inhibits DCLK1 activity by approximately 90% [4].
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: DCAMKL1
Ligand Sp. Type Action Value Parameter
NVP-TAE684 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.3 pKd
ruxolitinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.2 pKd
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.0 pKd
fedratinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 6.7 pKd
crizotinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.5 pKd
sunitinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 6.4 pKd
SU-14813 Small molecule or natural product Hs Inhibitor Inhibition 6.3 pKd
PHA-665752 Small molecule or natural product Hs Inhibitor Inhibition 5.8 pKd
BMS-387032 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 5.8 pKd
KW-2449 Small molecule or natural product Hs Inhibitor Inhibition 5.7 pKd
Displaying the top 10 most potent ligands  View all ligands in screen »

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. Ferguson FM, Nabet B, Raghavan S, Liu Y, Leggett AL, Kuljanin M, Kalekar RL, Yang A, He S, Wang J et al.. (2020) Discovery of a selective inhibitor of doublecortin like kinase 1. Nat Chem Biol, 16 (6): 635-643. [PMID:32251410]

3. Kim MH, Cierpicki T, Derewenda U, Krowarsch D, Feng Y, Devedjiev Y, Dauter Z, Walsh CA, Otlewski J, Bushweller JH et al.. (2003) The DCX-domain tandems of doublecortin and doublecortin-like kinase. Nat Struct Biol, 10 (5): 324-33. [PMID:12692530]

4. Milkiewicz KL, Weinberg LR, Albom MS, Angeles TS, Cheng M, Ghose AK, Roemmele RC, Theroff JP, Underiner TL, Zificsak CA et al.. (2010) Synthesis and structure-activity relationships of 1,2,3,4-tetrahydropyrido[2,3-b]pyrazines as potent and selective inhibitors of the anaplastic lymphoma kinase. Bioorg Med Chem, 18 (12): 4351-62. [PMID:20483621]

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]

How to cite this page

DCAMKL family: doublecortin like kinase 1. Last modified on 14/07/2020. Accessed on 19/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=2005.