activin A receptor type IL | Type I receptor serine/threonine kinases | IUPHAR/BPS Guide to PHARMACOLOGY

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activin A receptor type IL

Target not currently curated in GtoImmuPdb

Target id: 1784

Nomenclature: activin A receptor type IL

Abbreviated Name: ALK1

Family: Type I receptor serine/threonine kinases

Annotation status:  image of an orange circle Annotated and awaiting review. Please contact us if you can help with reviewing.  » Email us

Quaternary Structure: Complexes
Bone morphogenetic protein receptors
Gene and Protein Information
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 F3 Acvrl1 activin A receptor, type II-like 1
Rat 1 504 7q36 Acvrl1 activin A receptor like type 1
Previous and Unofficial Names
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
BRENDA
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
Orphanet
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Selected 3D Structures
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
EC Number: 2.7.11.30

Download all structure-activity data for this target as a CSV file

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] Hs Inhibition >8.3 pIC50 3
pIC50 >8.3 (IC50 <5x10-9 M) [3]
compound 13r [PMID: 23639540] Hs Inhibition >8.3 pIC50 3
pIC50 >8.3 (IC50 <5x10-9 M) [3]
LDN-214117 Hs Inhibition 7.6 pIC50 5
pIC50 7.6 (IC50 2.7x10-8 M) [5]
compound 13a [PMID: 23639540] Hs Inhibition 7.4 pIC50 3
pIC50 7.4 (IC50 4.21x10-8 M) [3]
ML347 Hs Inhibition 7.3 pIC50 3
pIC50 7.3 (IC50 4.6x10-8 M) [3]
panulisib Hs Inhibition 7.3 pIC50 4
pIC50 7.3 (IC50 4.7x10-8 M) [4]
Description: Using a radiometric protein kinase (33PanQinase activity) assay.
DiscoveRx KINOMEscan® screen
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: ACVRL1
Ligand Sp. Type Action Value Parameter
PP-242 Hs Inhibitor Inhibition 8.5 pKd
NVP-TAE684 Hs Inhibitor Inhibition 7.2 pKd
PD-173955 Hs Inhibitor Inhibition 7.2 pKd
dasatinib Hs Inhibitor Inhibition 6.3 pKd
vandetanib Hs Inhibitor Inhibition 6.3 pKd
JNJ-28312141 Hs Inhibitor Inhibition 5.7 pKd
lestaurtinib Hs Inhibitor Inhibition 5.7 pKd
fedratinib Hs Inhibitor Inhibition 5.6 pKd
SB203580 Hs Inhibitor Inhibition <5.5 pKd
ruboxistaurin 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
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 Hs Inhibitor Inhibition 15.1
dasatinib Hs Inhibitor Inhibition 15.9
dorsomorphin Hs Inhibitor Inhibition 21.6
alsterpaullone 2-cyanoethyl Hs Inhibitor Inhibition 53.6
bosutinib Hs Inhibitor Inhibition 67.6
TWS119 Hs Inhibitor Inhibition 70.3
Gö 6976 Hs Inhibitor Inhibition 73.6
alsterpaullone Hs Inhibitor Inhibition 76.2
aloisine A Hs Inhibitor Inhibition 76.2
VEGF receptor 2 kinase inhibitor IV Hs Inhibitor Inhibition 76.4
Displaying the top 10 most potent ligands  View all ligands in screen »
Clinically-Relevant Mutations and Pathophysiology
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. 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. 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]

4. 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]

5. 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]

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]

How to cite this page

Type I receptor serine/threonine kinases: activin A receptor type IL. Last modified on 10/07/2018. Accessed on 17/11/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1784.