activin A receptor type 1 | Type I receptor serine/threonine kinases | IUPHAR/BPS Guide to PHARMACOLOGY

activin A receptor type 1

Target id: 1785

Nomenclature: activin A receptor type 1

Abbreviated Name: ALK2

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

   GtoImmuPdb view: OFF :     Currently no data for activin A receptor type 1 in GtoImmuPdb

Quaternary Structure: Complexes
Bone morphogenetic protein receptors
Anti-Müllerian hormone receptors
Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 1 509 2q23-q24 ACVR1 activin A receptor type 1
Mouse 1 509 2 Acvr1 activin A receptor, type 1
Rat 1 509 3q21 Acvr1 activin A receptor type 1
Previous and Unofficial Names
serine/threonine-protein kinase receptor R1 | SKR1 | TGF-B superfamily receptor type I | TSR-I | ACTRI | Acvrlk2 | TSK-7L | ACVR1A | ACVRLK2 | Alk-2 | Alk8 | activin A receptor, type I | activin A receptor type I | activin A receptor
Database Links
BRENDA
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 kinase domain of type I activin receptor (ACVR1) in complex with FKBP12 and dorsomorphin
PDB Id:  3H9R
Resolution:  2.35Å
Species:  Human
References:  2
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 Affinity Units Reference
compound 13d [PMID: 23639540] Hs Inhibition >8.3 pIC50 4
pIC50 >8.3 (IC50 <5x10-9 M) [4]
compound 13r [PMID: 23639540] Hs Inhibition >8.3 pIC50 4
pIC50 >8.3 (IC50 <5x10-9 M) [4]
LDN-214117 Hs Inhibition 7.6 pIC50 5
pIC50 7.6 (IC50 2.4x10-8 M) [5]
ML347 Hs Inhibition 7.5 pIC50 4
pIC50 7.5 (IC50 3.2x10-8 M) [4]
compound 13a [PMID: 23639540] Hs Inhibition 7.3 pIC50 4
pIC50 7.3 (IC50 5.34x10-8 M) [4]
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: 3,6

Key to terms and symbols Click column headers to sort
Target used in screen: ACVR1
Ligand Sp. Type Action Affinity Units
PP-242 Hs Inhibitor Inhibition 8.4 pKd
NVP-TAE684 Hs Inhibitor Inhibition 7.5 pKd
lestaurtinib Hs Inhibitor Inhibition 7.1 pKd
KW-2449 Hs Inhibitor Inhibition 6.8 pKd
fedratinib Hs Inhibitor Inhibition 6.8 pKd
vandetanib Hs Inhibitor Inhibition 6.8 pKd
PD-173955 Hs Inhibitor Inhibition 6.8 pKd
JNJ-28312141 Hs Inhibitor Inhibition 6.4 pKd
crizotinib Hs Inhibitor Inhibition 6.4 pKd
staurosporine Hs Inhibitor Inhibition 6.3 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/ALK2(ACVR1)
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
dorsomorphin Hs Inhibitor Inhibition 15.4
alsterpaullone 2-cyanoethyl Hs Inhibitor Inhibition 58.8
Cdk1/2 inhibitor III Hs Inhibitor Inhibition 60.4
JNK inhibitor IX Hs Inhibitor Inhibition 72.9
PQ401 Hs Inhibitor Inhibition 76.2
alsterpaullone Hs Inhibitor Inhibition 79.7
compound 52 [PMID: 9677190] Hs Inhibitor Inhibition 80.3
aloisine A Hs Inhibitor Inhibition 83.8
D4476 Hs Inhibitor Inhibition 85.7
SB 218078 Hs Inhibitor Inhibition 85.8
Displaying the top 10 most potent ligands  View all ligands in screen »
Clinically-Relevant Mutations and Pathophysiology
Disease:  Fibrodysplasia ossificans progressiva
Disease Ontology: DOID:13374
OMIM: 135100
Orphanet: ORPHA337

References

Show »

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. Chaikuad A, Alfano I, Kerr G, Sanvitale CE, Boergermann JH, Triffitt JT, von Delft F, Knapp S, Knaus P, Bullock AN. (2012) Structure of the bone morphogenetic protein receptor ALK2 and implications for fibrodysplasia ossificans progressiva. J. Biol. Chem., 287 (44): 36990-8. [PMID:22977237]

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. 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 1. Last modified on 10/07/2018. Accessed on 14/11/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1785.