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activin A receptor type 1B

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Target not currently curated in GtoImmuPdb

Target id: 1787

Nomenclature: activin A receptor type 1B

Abbreviated Name: ALK4

Family: Type I receptor serine/threonine kinases

Contents:

Quaternary Structure: Complexes
Growth/differentiation factor receptors
Activin receptors
Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 1 505 12q13.13 ACVR1B activin A receptor type 1B
Mouse 1 505 15 56.48 cM Acvr1b activin A receptor, type 1B
Rat 1 505 7q36 Acvr1b activin A receptor type 1B
Previous and Unofficial Names Click here for help
activin A receptor | activin A receptor type IB | activin receptor-like kinase 4 | ActR-IB | ActRIB | ACVRLK4 | Alk4 | serine/threonine-protein kinase receptor R2 | SKR2
Database Links Click here for help
Alphafold P36896 (Hs), Q61271 (Mm), P80202 (Rn)
BRENDA 2.7.11.30
ChEMBL Target CHEMBL5310 (Hs)
Ensembl Gene ENSG00000135503 (Hs), ENSMUSG00000000532 (Mm), ENSRNOG00000006934 (Rn)
Entrez Gene 91 (Hs), 11479 (Mm), 29381 (Rn)
Human Protein Atlas ENSG00000135503 (Hs)
KEGG Enzyme 2.7.11.30
KEGG Gene hsa:91 (Hs), mmu:11479 (Mm), rno:29381 (Rn)
OMIM 601300 (Hs)
Pharos P36896 (Hs)
RefSeq Nucleotide NM_004302 (Hs), NM_007395 (Mm), NM_199230 (Rn)
RefSeq Protein NP_004293 (Hs), NP_031421 (Mm), NP_954700 (Rn)
UniProtKB P36896 (Hs), Q61271 (Mm), P80202 (Rn)
Wikipedia ACVR1B (Hs)
Enzyme Reaction Click here for help
EC Number: 2.7.11.30
Natural/Endogenous Ligands Click here for help
growth/differentiation factor-11 {Sp: Human}

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Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
vactosertib Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 7.9 pIC50 5
⤷ pIC50 7.9 (IC50 1.3x10-8 M) [5]
Description: Measured using Reaction Biology Corporation's HotSpot kinase assay
BMS-986260 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 7.5 pIC50 6
⤷ pIC50 7.5 (IC50 3.33x10-8 M) [6]
galunisertib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.1 pIC50 8
⤷ pIC50 7.1 (IC50 7.8x10-8 M) [8]
Description: Value determined usinfg the DiscoverX KINOMEscan platform.
compound 13r [PMID: 23639540] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.7 pIC50 3
⤷ pIC50 6.7 (IC50 1.83x10-7 M) [3]
compound 13d [PMID: 23639540] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.5 pIC50 3
⤷ pIC50 6.5 (IC50 3.26x10-7 M) [3]
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: 2,7
Key to terms and symbols Click column headers to sort
Target used in screen: ACVR1B
Ligand Sp. Type Action Value Parameter
JNJ-28312141 Small molecule or natural product Hs Inhibitor Inhibition 8.0 pKd
PP-242 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.2 pKd
lestaurtinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.1 pKd
PD-173955 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.0 pKd
NVP-TAE684 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.0 pKd
dasatinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.5 pKd
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.2 pKd
crizotinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.1 pKd
tamatinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 6.0 pKd
cediranib Small molecule or natural product Hs Inhibitor Inhibition 5.8 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: 1,4
Key to terms and symbols Click column headers to sort
Target used in screen: nd/ALK4(ACVR1B)
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
TGF-beta RI inhibitor III Small molecule or natural product Hs Inhibitor Inhibition 31.0 1.0 -6.0
TGF-beta RI kinase inhibitor Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 43.2 -3.0 -4.0
SB 202474 Small molecule or natural product Hs Inhibitor Inhibition 86.5 94.0 97.0
SKI II Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 89.5 104.0 110.0
PDGF RTK inhibitor Small molecule or natural product Hs Inhibitor Inhibition 92.1 126.0 96.0
Cdk1/2 inhibitor III Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 92.2 7.0 -4.0
PD98059 Small molecule or natural product Hs Inhibitor Inhibition 92.5 111.0 108.0
mubritinib Small molecule or natural product Hs Inhibitor Inhibition 92.8
PDGF receptor tyrosine kinase inhibitor IV Small molecule or natural product Hs Inhibitor Inhibition 92.9 117.0 91.0
KN-93 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 93.2 96.0 102.0
Displaying the top 10 most potent ligands  View all ligands in screen »
Immuno Process Associations
Immuno Process:  Immune regulation
Immuno Process:  Immune system development

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. Gao Y, Davies SP, Augustin M, Woodward A, Patel UA, Kovelman R, Harvey KJ. (2013) A broad activity screen in support of a chemogenomic map for kinase signalling research and drug discovery. Biochem J, 451 (2): 313-28. [PMID:23398362]

5. Jin CH, Krishnaiah M, Sreenu D, Subrahmanyam VB, Rao KS, Lee HJ, Park SJ, Park HJ, Lee K, Sheen YY et al.. (2014) Discovery of N-((4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-5-(6-methylpyridin-2-yl)-1H-imidazol-2-yl)methyl)-2-fluoroaniline (EW-7197): a highly potent, selective, and orally bioavailable inhibitor of TGF-β type I receptor kinase as cancer immunotherapeutic/antifibrotic agent. J Med Chem, 57 (10): 4213-38. [PMID:24786585]

6. Velaparthi U, Darne CP, Warrier J, Liu P, Rahaman H, Augustine-Rauch K, Parrish K, Yang Z, Swanson J, Brown J et al.. (2020) Discovery of BMS-986260, a Potent, Selective, and Orally Bioavailable TGFβR1 Inhibitor as an Immuno-oncology Agent. ACS Med Chem Lett, 11 (2): 172-178. DOI: 10.1021/acsmedchemlett.9b00552 [PMID:32071685]

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]

8. Yingling JM, McMillen WT, Yan L, Huang H, Sawyer JS, Graff J, Clawson DK, Britt KS, Anderson BD, Beight DW et al.. (2018) Preclinical assessment of galunisertib (LY2157299 monohydrate), a first-in-class transforming growth factor-β receptor type I inhibitor. Oncotarget, 9 (6): 6659-6677. [PMID:29467918]

How to cite this page

Type I receptor serine/threonine kinases: activin A receptor type 1B. Last modified on 11/02/2020. Accessed on 02/12/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=1787.