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activin A receptor type IL

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Target id: 1784

Nomenclature: activin A receptor type IL

Abbreviated Name: ALK1

Family: Type I receptor serine/threonine kinases

Contents:

Quaternary Structure: Complexes
Bone morphogenetic protein receptors
Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 1 503 12q13.13 ACVRL1 activin A receptor like type 1
Mouse 1 502 15 F1 Acvrl1 activin A receptor, type II-like 1
Rat 1 504 7q36 Acvrl1 activin A receptor like type 1
Previous and Unofficial Names Click here for help
SKR3 | ACVRLK1 | HHT | HHT2 | ORW2 | SETHKIR | TGF-B superfamily receptor type I | TSR-I | activin receptor-like kinase-1 | Serine/threonine-protein kinase receptor R3 | activin A receptor, type II-like 1 | activin A receptor
Database Links Click here for help
Alphafold P37023 (Hs), Q61288 (Mm), P80203 (Rn)
BRENDA 2.7.11.30
ChEMBL Target CHEMBL5311 (Hs), CHEMBL4105896 (Mm)
Ensembl Gene ENSG00000139567 (Hs), ENSMUSG00000000530 (Mm), ENSRNOG00000028713 (Rn)
Entrez Gene 94 (Hs), 11482 (Mm), 25237 (Rn)
Human Protein Atlas ENSG00000139567 (Hs)
KEGG Enzyme 2.7.11.30
KEGG Gene hsa:94 (Hs), mmu:11482 (Mm), rno:25237 (Rn)
OMIM 601284 (Hs)
Orphanet ORPHA117764 (Hs)
Pharos P37023 (Hs)
RefSeq Nucleotide NM_000020 (Hs), NM_009612 (Mm), NM_022441 (Rn)
RefSeq Protein NP_000011 (Hs), NP_033742 (Mm), NP_071886 (Rn)
UniProtKB P37023 (Hs), Q61288 (Mm), P80203 (Rn)
Wikipedia ACVRL1 (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of the ACVRL1 (ALK1) kinase domain bound to LDN-193189
PDB Id:  3MY0
Resolution:  2.65Å
Species:  Human
References: 
Enzyme Reaction Click here for help
EC Number: 2.7.11.30

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
compound 13d [PMID: 23639540] Small molecule or natural product Click here for species-specific activity table Hs Inhibition >8.3 pIC50 4
⤷ pIC50 >8.3 (IC50 <5x10-9 M) [4]
compound 13r [PMID: 23639540] Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition >8.3 pIC50 4
⤷ pIC50 >8.3 (IC50 <5x10-9 M) [4]
LDN-214117 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.6 pIC50 6
⤷ pIC50 7.6 (IC50 2.7x10-8 M) [6]
compound 13a [PMID: 23639540] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.4 pIC50 4
⤷ pIC50 7.4 (IC50 4.21x10-8 M) [4]
ML347 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.3 pIC50 4
⤷ pIC50 7.3 (IC50 4.6x10-8 M) [4]
panulisib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.3 pIC50 5
⤷ pIC50 7.3 (IC50 4.7x10-8 M) [5]
Description: Using a radiometric protein kinase (33PanQinase activity) assay.
zilurgisertib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.5 pIC50 2
⤷ pIC50 6.5 (IC50 3.23x10-7 M) [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: 3,7
Key to terms and symbols Click column headers to sort
Target used in screen: ACVRL1
Ligand Sp. Type Action Value Parameter
PP-242 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.5 pKd
NVP-TAE684 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.2 pKd
PD-173955 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.2 pKd
dasatinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.3 pKd
vandetanib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 6.3 pKd
JNJ-28312141 Small molecule or natural product Hs Inhibitor Inhibition 5.7 pKd
lestaurtinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 5.7 pKd
fedratinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 5.6 pKd
SB203580 Small molecule or natural product Immunopharmacology Ligand Hs Inhibitor Inhibition <5.5 pKd
ruboxistaurin Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition <5.5 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: ...1
Key to terms and symbols Click column headers to sort
Target used in screen: nd/ALK1(ACVRL1)
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
Cdk1/2 inhibitor III Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 15.1
dasatinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 15.9
dorsomorphin Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 21.6
alsterpaullone 2-cyanoethyl Small molecule or natural product Hs Inhibitor Inhibition 53.6
bosutinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 67.6
TWS119 Small molecule or natural product Hs Inhibitor Inhibition 70.3
Gö 6976 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 73.6
aloisine A Small molecule or natural product Hs Inhibitor Inhibition 76.2
alsterpaullone Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 76.2
VEGF receptor 2 kinase inhibitor IV Small molecule or natural product Hs Inhibitor Inhibition 76.4
Displaying the top 10 most potent ligands  View all ligands in screen »
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Heritable pulmonary arterial hypertension
Orphanet: ORPHA275777
Disease:  Telangiectasia, hereditary hemorrhagic, type 2
Synonyms: Hereditary hemorrhagic telangiectasia [Orphanet: ORPHA774] [Disease Ontology: DOID:1270]
Disease Ontology: DOID:1270
OMIM: 600376
Orphanet: ORPHA774

References

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1. 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]

2. Arista L, Babu S, Bian J, Cui K, Dillon MP, Lattmann R, Li J, Liao L, Lizos D, Ramos R et al.. (2021) Aminopyridine derivatives and their use as selective alk-2 inhibitors. Patent number: US20210155606A1. Assignee: Novartis AG. Priority date: 20/07/2016. Publication date: 27/05/2021.

3. 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]

4. Engers DW, Frist AY, Lindsley CW, Hong CC, Hopkins CR. (2013) Synthesis and structure-activity relationships of a novel and selective bone morphogenetic protein receptor (BMP) inhibitor derived from the pyrazolo[1.5-a]pyrimidine scaffold of dorsomorphin: the discovery of ML347 as an ALK2 versus ALK3 selective MLPCN probe. Bioorg Med Chem Lett, 23 (11): 3248-52. [PMID:23639540]

5. Jalota-Badhwar A, Bhatia DR, Boreddy S, Joshi A, Venkatraman M, Desai N, Chaudhari S, Bose J, Kolla LS, Deore V et al.. (2015) P7170: A Novel Molecule with Unique Profile of mTORC1/C2 and Activin Receptor-like Kinase 1 Inhibition Leading to Antitumor and Antiangiogenic Activity. Mol Cancer Ther, 14 (5): 1095-106. [PMID:25700704]

6. Mohedas AH, Wang Y, Sanvitale CE, Canning P, Choi S, Xing X, Bullock AN, Cuny GD, Yu PB. (2014) Structure-activity relationship of 3,5-diaryl-2-aminopyridine ALK2 inhibitors reveals unaltered binding affinity for fibrodysplasia ossificans progressiva causing mutants. J Med Chem, 57 (19): 7900-15. [PMID:25101911]

7. 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

Type I receptor serine/threonine kinases: activin A receptor type IL. Last modified on 04/02/2022. Accessed on 11/12/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=1784.