colony stimulating factor 1 receptor

Target id: 1806

Nomenclature: colony stimulating factor 1 receptor

Abbreviated Name: CSFR

Family: Type III RTKs: PDGFR, CSFR, Kit, FLT3 receptor family

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 1 972 5q32 CSF1R colony stimulating factor 1 receptor
Mouse 1 977 18 D Csf1r colony stimulating factor 1 receptor
Rat 1 1022 18 q12.1 Csf1r colony stimulating factor 1 receptor
Previous and Unofficial Names
CD115
C-FMS
McDonough feline sarcoma viral (v-fms) oncogene homolog
CSF-1 receptor
macrophage colony-stimulating factor 1 receptor
Csfmr
Fim-2
M-CSFR
Database Links
BRENDA
Ensembl Gene
Entrez Gene
ExplorEnz
GeneCards
GenitoUrinary Development Molecular Anatomy Project
HomoloGene
Human Protein Reference Database
InterPro
KEGG Enzyme
KEGG Gene
NeXtProt
OMIM
Orphanet
PhosphoSitePlus
RefSeq Nucleotide
RefSeq Protein
TreeFam
UniGene
UniProtKB
Wikipedia
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  cFMS tyrosine kinase (tie2 KID) in complex with an arylamide inhibitor
PDB Id:  2I1M
Resolution:  1.8Å
Species:  Human
References:  24
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of FMS KINASE domain with a small molecular inhibitor, PLX3397.
PDB Id:  4R7H
Ligand:  pexidartinib
Resolution:  2.8Å
Species:  Human
References:  27
Enzyme Reaction
EC Number: 2.7.10.1
Natural/Endogenous Ligands
IL-34 {Sp: Human}
M-CSF {Sp: Human}

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
Ki-20227 Hs Inhibition 9.1 pKd 9
pKd 9.1 (Kd 8.3x10-10 M) [9]
AC710 Hs Inhibition 8.8 pKd 18
pKd 8.8 (Kd 1.57x10-9 M) [18]
GW-2580 Hs Inhibition 8.7 pKd 9
pKd 8.7 (Kd 2.2x10-9 M) [9]
JNJ-28312141 Hs Inhibition 8.5 pKd 9
pKd 8.5 (Kd 3.2x10-9 M) [9]
quizartinib Hs Inhibition 7.9 pKd 6
pKd 7.9 (Kd 1.2x10-8 M) [6]
crenolanib Hs Inhibition 7.5 pKd 15
pKd 7.5 (Kd 3x10-8 M) [15]
JNJ-28312141 Hs Inhibition 9.2 pIC50 19
pIC50 9.2 (IC50 6.9x10-10 M) [19]
BLZ945 Hs Inhibition 9.0 pIC50 26
pIC50 9.0 (IC50 1x10-9 M) [26]
Ki-20227 Hs Inhibition 8.7 pIC50 22
pIC50 8.7 (IC50 2x10-9 M) [22]
linifanib Hs Inhibition 8.5 pIC50 2
pIC50 8.5 (IC50 3x10-9 M) [2]
JNJ-40346527 Hs Inhibition 8.5 pIC50 12
pIC50 8.5 (IC50 3.2x10-9 M) [12]
cerdulatinib Hs Inhibition 8.3 pIC50 7
pIC50 8.3 (IC50 5x10-9 M) [7]
AZD6495 Hs Inhibition 8.2 pIC50 25
pIC50 8.2 (IC50 6x10-9 M) [25]
ARRY-382 Hs Inhibition 8.1 pIC50 4
pIC50 8.1 (IC50 9x10-9 M) [4]
dovitinib Hs Inhibition 7.4 – 8.5 pIC50 23,28
pIC50 7.4 – 8.5 (IC50 3.6x10-8 – 3x10-9 M) [23,28]
pexidartinib Hs Inhibition 7.9 pIC50 27
pIC50 7.9 (IC50 1.3x10-8 M) [27]
TG02 Hs Inhibition 7.6 pIC50 13
pIC50 7.6 (IC50 2.7x10-8 M) [13]
CC-223 Hs Inhibition 7.6 pIC50 20
pIC50 7.6 (IC50 2.8x10-8 M) [20]
GW-2580 Hs Inhibition 7.2 pIC50 8
pIC50 7.2 (IC50 6x10-8 M) [8]
cediranib Hs Inhibition 7.0 pIC50 29
pIC50 7.0 (IC50 1.1x10-7 M) [29]
pazopanib Hs Inhibition 6.8 pIC50 14
pIC50 6.8 (IC50 1.46x10-7 M) [14]
GTP-14564 Hs Inhibition 6.5 pIC50 21
pIC50 6.5 (IC50 3x10-7 M) [21]
tandutinib Hs Inhibition 5.5 pIC50 16
pIC50 5.5 (IC50 3.43x10-6 M) [16]
Agonists
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Affinity Units Reference
IL-34 {Sp: Human} Hs Agonist - - 17
[17]
Antibodies
Key to terms and symbols Click column headers to sort
Antibody Sp. Action Affinity Units Reference
AMG820 Hs Binding >9.3 pKd 5
pKd >9.3 (Kd <5.5x10-10 M) [5]
cabiralizumab Hs Binding >9.0 pKd 31
pKd >9.0 (Kd <1x10-9 M) [31]
LY3022855 Hs Binding 10.1 pEC50 10
pEC50 10.1 (EC50 9x10-11 M) [10]
Description: Measured in an ELISA binding 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: 9,30

Key to terms and symbols Click column headers to sort
Target used in screen: CSF1R
Ligand Sp. Type Action Affinity Units
dasatinib Hs Inhibitor Inhibition 9.2 pKd
PD-173955 Hs Inhibitor Inhibition 9.2 pKd
Ki-20227 Hs Inhibitor Inhibition 9.1 pKd
foretinib Hs Inhibitor Inhibition 8.7 pKd
GW-2580 Hs Inhibitor Inhibition 8.7 pKd
sunitinib Hs Inhibitor Inhibition 8.6 pKd
JNJ-28312141 Hs Inhibitor Inhibition 8.5 pKd
linifanib Hs Inhibitor Inhibition 8.5 pKd
SU-14813 Hs Inhibitor Inhibition 8.4 pKd
tandutinib Hs Inhibitor Inhibition 8.3 pKd
Target used in screen: CSF1R-autoinhibited
Ligand Sp. Type Action Affinity Units
dasatinib Hs Inhibitor Inhibition 9.0 pKd
staurosporine Hs Inhibitor Inhibition 8.6 pKd
sunitinib Hs Inhibitor Inhibition 8.4 pKd
PD-173955 Hs Inhibitor Inhibition 7.8 pKd
Ki-20227 Hs Inhibitor Inhibition 7.7 pKd
GW-2580 Hs Inhibitor Inhibition 7.6 pKd
midostaurin Hs Inhibitor Inhibition 6.7 pKd
lestaurtinib Hs Inhibitor Inhibition 6.2 pKd
quizartinib Hs Inhibitor Inhibition 6.0 pKd
bosutinib Hs Inhibitor Inhibition 6.0 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: 3,11

Key to terms and symbols Click column headers to sort
Target used in screen: Fms/FMS
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
dasatinib Hs Inhibitor Inhibition 0.8
staurosporine Hs Inhibitor Inhibition 1.8 0.5 0.0
sorafenib Hs Inhibitor Inhibition 5.6
Cdk2 inhibitor IV Hs Inhibitor Inhibition 5.7 1.0 2.0
midostaurin Hs Inhibitor Inhibition 6.6 0.0 1.0
sunitinib Hs Inhibitor Inhibition 7.3
SU11652 Hs Inhibitor Inhibition 7.4 0.0 0.0
masitinib Hs Inhibitor Inhibition 8.4
PDGF RTK inhibitor Hs Inhibitor Inhibition 10.5 0.0 -1.0
Cdk1/2 inhibitor III Hs Inhibitor Inhibition 10.6 5.0 0.0
Displaying the top 10 most potent ligands  View all ligands in screen »
Clinically-Relevant Mutations and Pathophysiology
Disease:  Leukoencephalopathy, diffuse hereditary, with spheroids
Synonyms: Hereditary diffuse leukoencephalopathy with axonal spheroids and pigmented glia [Orphanet: ORPHA313808]
OMIM: 221820
Orphanet: ORPHA313808

References

Show »

1. Adams JL, Smothers J, Srinivasan R, Hoos A. (2015) Big opportunities for small molecules in immuno-oncology. Nat Rev Drug Discov14 (9): 603-22. [PMID:26228631]

2. Albert DH, Tapang P, Magoc TJ, Pease LJ, Reuter DR, Wei RQ, Li J, Guo J, Bousquet PF, Ghoreishi-Haack NS et al.. (2006) Preclinical activity of ABT-869, a multitargeted receptor tyrosine kinase inhibitor. Mol. Cancer Ther.5 (4): 995-1006. [PMID:16648571]

3. 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]

4. Bendell J et al.. A Phase 1 Study of ARRY-382, an Oral Inhibitor of Colony-stimulating Factor-1 Receptor (CSF1R), in Patients with Advanced or Metastatic Cancers. Accessed on 14/04/2016. Modified on 14/04/2016. Arraybiopharma.com, http://www.arraybiopharma.com/files/3014/4501/8593/382-101_AACR-NCI-EORTC_poster.pdf

5. Brasel KA, Foster S, Cerretti DP, Sun J, Smothers JF, Mehlin C. (2009) Human c-fms antigen binding proteins. Patent number: WO2009026303 A1. Assignee: Amgen Inc.. Priority date: 21/08/2007. Publication date: 26/02/2009.

6. Chao Q, Sprankle KG, Grotzfeld RM, Lai AG, Carter TA, Velasco AM, Gunawardane RN, Cramer MD, Gardner MF, James J et al.. (2009) Identification of N-(5-tert-butyl-isoxazol-3-yl)-N'-{4-[7-(2-morpholin-4-yl-ethoxy)imidazo[2,1-b][1,3]benzothiazol-2-yl]phenyl}urea dihydrochloride (AC220), a uniquely potent, selective, and efficacious FMS-like tyrosine kinase-3 (FLT3) inhibitor. J. Med. Chem.52 (23): 7808-16. [PMID:19754199]

7. Coffey G, Betz A, DeGuzman F, Pak Y, Inagaki M, Baker DC, Hollenbach SJ, Pandey A, Sinha U. (2014) The novel kinase inhibitor PRT062070 (Cerdulatinib) demonstrates efficacy in models of autoimmunity and B-cell cancer. J. Pharmacol. Exp. Ther.351 (3): 538-48. [PMID:25253883]

8. Conway JG, McDonald B, Parham J, Keith B, Rusnak DW, Shaw E, Jansen M, Lin P, Payne A, Crosby RM et al.. (2005) Inhibition of colony-stimulating-factor-1 signaling in vivo with the orally bioavailable cFMS kinase inhibitor GW2580. Proc. Natl. Acad. Sci. U.S.A.102 (44): 16078-83. [PMID:16249345]

9. 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]

10. Doody JF, Li Y. (2011) Antibodies against csf-1r. Patent number: WO2011123381 A1. Assignee: Imclone Llc. Priority date: 01/04/2010. Publication date: 06/10/2011.

11. 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]

12. Genovese MC, Hsia E, Belkowski SM, Chien C, Masterson T, Thurmond RL, Manthey CL, Yan XD, Ge T, Franks C et al.. (2015) Results from a Phase IIA Parallel Group Study of JNJ-40346527, an Oral CSF-1R Inhibitor, in Patients with Active Rheumatoid Arthritis despite Disease-modifying Antirheumatic Drug Therapy. J. Rheumatol.42 (10): 1752-60. [PMID:26233509]

13. Goh KC, Novotny-Diermayr V, Hart S, Ong LC, Loh YK, Cheong A, Tan YC, Hu C, Jayaraman R, William AD et al.. (2012) TG02, a novel oral multi-kinase inhibitor of CDKs, JAK2 and FLT3 with potent anti-leukemic properties. Leukemia26 (2): 236-43. [PMID:21860433]

14. Harris PA, Boloor A, Cheung M, Kumar R, Crosby RM, Davis-Ward RG, Epperly AH, Hinkle KW, Hunter 3rd RN, Johnson JH et al.. (2008) Discovery of 5-[[4-[(2,3-dimethyl-2H-indazol-6-yl)methylamino]-2-pyrimidinyl]amino]-2-methyl-benzenesulfonamide (Pazopanib), a novel and potent vascular endothelial growth factor receptor inhibitor. J. Med. Chem.51 (15): 4632-40. [PMID:18620382]

15. Heinrich MC, Griffith D, McKinley A, Patterson J, Presnell A, Ramachandran A, Debiec-Rychter M. (2012) Crenolanib inhibits the drug-resistant PDGFRA D842V mutation associated with imatinib-resistant gastrointestinal stromal tumors. Clin. Cancer Res.18 (16): 4375-84. [PMID:22745105]

16. Kelly LM, Yu JC, Boulton CL, Apatira M, Li J, Sullivan CM, Williams I, Amaral SM, Curley DP, Duclos N et al.. (2002) CT53518, a novel selective FLT3 antagonist for the treatment of acute myelogenous leukemia (AML). Cancer Cell1 (5): 421-32. [PMID:12124172]

17. Lin H, Lee E, Hestir K, Leo C, Huang M, Bosch E, Halenbeck R, Wu G, Zhou A, Behrens D et al.. (2008) Discovery of a cytokine and its receptor by functional screening of the extracellular proteome. Science320 (5877): 807-11. [PMID:18467591]

18. Liu G, Campbell BT, Holladay MW, Ford Pulido JM, Hua H, Gitnick D, Gardner MF, James J, Breider MA, Brigham D et al.. (2012) Discovery of AC710, a Globally Selective Inhibitor of Platelet-Derived Growth Factor Receptor-Family Kinases. ACS Med Chem Lett3 (12): 997-1002. [PMID:24900421]

19. Manthey CL, Johnson DL, Illig CR, Tuman RW, Zhou Z, Baker JF, Chaikin MA, Donatelli RR, Franks CF, Zeng L et al.. (2009) JNJ-28312141, a novel orally active colony-stimulating factor-1 receptor/FMS-related receptor tyrosine kinase-3 receptor tyrosine kinase inhibitor with potential utility in solid tumors, bone metastases, and acute myeloid leukemia. Mol. Cancer Ther.8 (11): 3151-61. [PMID:19887542]

20. Mortensen DS, Perrin-Ninkovic SM, Shevlin G, Zhao J, Packard G, Bahmanyar S, Correa M, Elsner J, Harris R, Lee BG et al.. (2015) Discovery of mammalian target of rapamycin (mTOR) kinase inhibitor CC-223. J. Med. Chem.58 (13): 5323-33. [PMID:26083478]

21. Murata K, Kumagai H, Kawashima T, Tamitsu K, Irie M, Nakajima H, Suzu S, Shibuya M, Kamihira S, Nosaka T et al.. (2003) Selective cytotoxic mechanism of GTP-14564, a novel tyrosine kinase inhibitor in leukemia cells expressing a constitutively active Fms-like tyrosine kinase 3 (FLT3). J. Biol. Chem.278 (35): 32892-8. [PMID:12815052]

22. Ohno H, Kubo K, Murooka H, Kobayashi Y, Nishitoba T, Shibuya M, Yoneda T, Isoe T. (2006) A c-fms tyrosine kinase inhibitor, Ki20227, suppresses osteoclast differentiation and osteolytic bone destruction in a bone metastasis model. Mol. Cancer Ther.5 (11): 2634-43. [PMID:17121910]

23. Renhowe PA, Pecchi S, Shafer CM, Machajewski TD, Jazan EM, Taylor C, Antonios-McCrea W, McBride CM, Frazier K, Wiesmann M et al.. (2009) Design, structure-activity relationships and in vivo characterization of 4-amino-3-benzimidazol-2-ylhydroquinolin-2-ones: a novel class of receptor tyrosine kinase inhibitors. J. Med. Chem.52 (2): 278-92. [PMID:19113866]

24. Schubert C, Schalk-Hihi C, Struble GT, Ma HC, Petrounia IP, Brandt B, Deckman IC, Patch RJ, Player MR, Spurlino JC et al.. (2007) Crystal structure of the tyrosine kinase domain of colony-stimulating factor-1 receptor (cFMS) in complex with two inhibitors. J. Biol. Chem.282 (6): 4094-101. [PMID:17132624]

25. Scott DA, Bell KJ, Campbell CT, Cook DJ, Dakin LA, Del Valle DJ, Drew L, Gero TW, Hattersley MM, Omer CA et al.. (2009) 3-amido-4-anilinoquinolines as CSF-1R kinase inhibitors 2: Optimization of the PK profile. Bioorg. Med. Chem. Lett.19 (3): 701-5. [PMID:19114305]

26. Strachan DC, Ruffell B, Oei Y, Bissell MJ, Coussens LM, Pryer N, Daniel D. (2013) CSF1R inhibition delays cervical and mammary tumor growth in murine models by attenuating the turnover of tumor-associated macrophages and enhancing infiltration by CD8(+) T cells. Oncoimmunology2 (12): e26968. [PMID:24498562]

27. Tap WD, Wainberg ZA, Anthony SP, Ibrahim PN, Zhang C, Healey JH, Chmielowski B, Staddon AP, Cohn AL, Shapiro GI et al.. (2015) Structure-Guided Blockade of CSF1R Kinase in Tenosynovial Giant-Cell Tumor. N. Engl. J. Med.373 (5): 428-37. [PMID:26222558]

28. Trudel S, Li ZH, Wei E, Wiesmann M, Chang H, Chen C, Reece D, Heise C, Stewart AK. (2005) CHIR-258, a novel, multitargeted tyrosine kinase inhibitor for the potential treatment of t(4;14) multiple myeloma. Blood105 (7): 2941-8. [PMID:15598814]

29. Wedge SR, Kendrew J, Hennequin LF, Valentine PJ, Barry ST, Brave SR, Smith NR, James NH, Dukes M, Curwen JO et al.. (2005) AZD2171: a highly potent, orally bioavailable, vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor for the treatment of cancer. Cancer Res.65 (10): 4389-400. [PMID:15899831]

30. 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]

31. Wong J, Vasquez M. (2011) Antibodies That Bind CSF1R. Patent number: US20110274683 A1. Assignee: Five Prime Therapeutics, Inc.. Priority date: 04/05/2010. Publication date: 10/11/2011.

How to cite this page

Type III RTKs: PDGFR, CSFR, Kit, FLT3 receptor family: colony stimulating factor 1 receptor. Last modified on 15/04/2016. Accessed on 27/07/2016. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1806.