c-ros oncogene 1, receptor tyrosine kinase | Type XVII RTKs: ROS receptors | IUPHAR/BPS Guide to PHARMACOLOGY

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c-ros oncogene 1, receptor tyrosine kinase

Target not currently curated in GtoImmuPdb

Target id: 1840

Nomenclature: c-ros oncogene 1, receptor tyrosine kinase

Abbreviated Name: ROS

Family: Type XVII RTKs: ROS receptors

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

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 1 2347 6q21-q22 ROS1 ROS proto-oncogene 1, receptor tyrosine kinase
Mouse 1 2340 10 Ros1 Ros1 proto-oncogene
Rat 1 2338 20q11 Ros1 ROS proto-oncogene 1
Previous and Unofficial Names
c-ros-1 | MCF3 | heart - derived c - ros - 1 proto - oncogene | ROS1C | ROS proto-oncogene 1 , receptor tyrosine kinase | ROS proto-oncogene 1
Database Links
BRENDA
CATH/Gene3D
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  Structure of Human ROS1 Kinase Domain in Complex with PF-06463922
PDB Id:  4UXL
Ligand:  lorlantinib
Resolution:  2.4Å
Species:  Human
References:  8
Enzyme Reaction
EC Number: 2.7.10.1

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 Parameter Reference
lorlantinib Hs Inhibition 11.3 pKi 4
pKi 11.3 (Ki 5x10-12 M) [4]
compound 8e [PMID: 24432909] Hs Inhibition 10.7 pKi 5
pKi 10.7 (Ki 2x10-11 M) [5]
Description: Value calculated from tight-binding (Morrison) equation for competitive inhibitors tested in a Pfizer mobility shift assay.
gilteritinib Hs Inhibition ~8.8 pIC50 6
pIC50 ~8.8 (IC50 ~1.5x10-9 M) [6]
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: 2,7

Key to terms and symbols Click column headers to sort
Target used in screen: ROS1
Ligand Sp. Type Action Affinity Parameter
NVP-TAE684 Hs Inhibitor Inhibition 9.3 pKd
crizotinib Hs Inhibitor Inhibition 8.4 pKd
foretinib Hs Inhibitor Inhibition 7.8 pKd
GSK-1838705A Hs Inhibitor Inhibition 7.8 pKd
lestaurtinib Hs Inhibitor Inhibition 7.6 pKd
tamatinib Hs Inhibitor Inhibition 7.5 pKd
staurosporine Hs Inhibitor Inhibition 7.5 pKd
midostaurin Hs Inhibitor Inhibition 6.4 pKd
fedratinib Hs Inhibitor Inhibition 6.2 pKd
tozasertib Hs Inhibitor Inhibition 6.2 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: 1,3

Key to terms and symbols Click column headers to sort
Target used in screen: Ros/ROS(ROS1)
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
staurosporine Hs Inhibitor Inhibition 0.9 3.5 1.5
Gö 6976 Hs Inhibitor Inhibition 1.2 1.0 3.0
K-252a Hs Inhibitor Inhibition 1.6 21.0 3.0
SB 218078 Hs Inhibitor Inhibition 1.6 94.0 81.0
Cdk1/2 inhibitor III Hs Inhibitor Inhibition 1.7 70.0 16.0
midostaurin Hs Inhibitor Inhibition 6.5 63.0 50.0
GSK-3 inhibitor XIII Hs Inhibitor Inhibition 16.7 84.0 40.0
pazopanib Hs Inhibitor Inhibition 17.0
aloisine A Hs Inhibitor Inhibition 26.3 93.0 82.0
PDGF RTK inhibitor Hs Inhibitor Inhibition 26.7 79.0 52.0
Displaying the top 10 most potent ligands  View all ligands in screen »

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. 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]

4. Helen Y. Zou HY, Engstrom LR, Li Q, Lu MW, Tang RW, Wang H, Tsaparikos K, Timofeevski S, Lam J, Yamazaki J et al.. (2013) Abstract A277: PF-06463922, a novel ROS1/ALK inhibitor, demonstrates sub-nanomolar potency against oncogenic ROS1 fusions and capable of blocking the resistant ROS1G2032R mutant in preclinical tumor models. Mol Cancer Ther, (12): A277 Meeting abstract.

5. Huang Q, Johnson TW, Bailey S, Brooun A, Bunker KD, Burke BJ, Collins MR, Cook AS, Cui JJ, Dack KN et al.. (2014) Design of potent and selective inhibitors to overcome clinical anaplastic lymphoma kinase mutations resistant to crizotinib. J. Med. Chem., 57 (4): 1170-87. [PMID:24432909]

6. Lee LY, Hernandez D, Rajkhowa T, Smith SC, Raman JR, Nguyen B, Small D, Levis M. (2017) Preclinical studies of gilteritinib, a next-generation FLT3 inhibitor. Blood, 129 (2): 257-260. [PMID:27908881]

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. Zou HY, Li Q, Engstrom LD, West M, Appleman V, Wong KA, McTigue M, Deng YL, Liu W, Brooun A et al.. (2015) PF-06463922 is a potent and selective next-generation ROS1/ALK inhibitor capable of blocking crizotinib-resistant ROS1 mutations. Proc. Natl. Acad. Sci. U.S.A., 112 (11): 3493-8. [PMID:25733882]

How to cite this page

Type XVII RTKs: ROS receptors: c-ros oncogene 1, receptor tyrosine kinase. Last modified on 29/11/2018. Accessed on 20/02/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1840.