Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTC70AJ)

• DTT Name: Granulocyte colony-stimulating factor receptor (G-CSF-R)
• Synonyms: c-fms; GCSFR; GCSF receptor; G-CSF receptor; Fms proto-oncogene; CD114
• Gene Name: CSF3R
• DTT Type: Successful target; [1]
• BioChemical Class: Cytokine receptor
• UniProt ID: CSF3R_HUMAN
• TTD ID: T98913
• Sequence:
  MARLGNCSLTWAALIILLLPGSLEECGHISVSAPIVHLGDPITASCIIKQNCSHLDPEPQ
  ILWRLGAELQPGGRQQRLSDGTQESIITLPHLNHTQAFLSCCLNWGNSLQILDQVELRAG
  YPPAIPHNLSCLMNLTTSSLICQWEPGPETHLPTSFTLKSFKSRGNCQTQGDSILDCVPK
  DGQSHCCIPRKHLLLYQNMGIWVQAENALGTSMSPQLCLDPMDVVKLEPPMLRTMDPSPE
  AAPPQAGCLQLCWEPWQPGLHINQKCELRHKPQRGEASWALVGPLPLEALQYELCGLLPA
  TAYTLQIRCIRWPLPGHWSDWSPSLELRTTERAPTVRLDTWWRQRQLDPRTVQLFWKPVP
  LEEDSGRIQGYVVSWRPSGQAGAILPLCNTTELSCTFHLPSEAQEVALVAYNSAGTSRPT
  PVVFSESRGPALTRLHAMARDPHSLWVGWEPPNPWPQGYVIEWGLGPPSASNSNKTWRME
  QNGRATGFLLKENIRPFQLYEIIVTPLYQDTMGPSQHVYAYSQEMAPSHAPELHLKHIGK
  TWAQLEWVPEPPELGKSPLTHYTIFWTNAQNQSFSAILNASSRGFVLHGLEPASLYHIHL
  MAASQAGATNSTVLTLMTLTPEGSELHIILGLFGLLLLLTCLCGTAWLCCSPNRKNPLWP
  SVPDPAHSSLGSWVPTIMEEDAFQLPGLGTPPITKLTVLEEDEKKPVPWESHNSSETCGL
  PTLVQTYVLQGDPRAVSTQPQSQSGTSDQVLYGQLLGSPTSPGPGHYLRCDSTQPLLAGL
  TPSPKSYENLWFQASPLGTLVTPAPSQEDDCVFGPLLNFPLLQGIRVHGMEALGSF
• Function: Plays a crucial role in the proliferation, differientation and survival of cells along the neutrophilic lineage. In addition it may function in some adhesion or recognition events at the cell surface. Receptor for granulocyte colony-stimulating factor (CSF3), essential for granulocytic maturation.
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  PI3K-Akt signaling pathway (hsa04151)
  Jak-STAT signaling pathway (hsa04630)
  Hematopoietic cell lineage (hsa04640)
  Pathways in cancer (hsa05200)
• Reactome Pathway:
  Transcriptional regulation of granulopoiesis (R-HSA-9616222)
  Signaling by CSF3 (G-CSF) (R-HSA-9674555)
  Inactivation of CSF3 (G-CSF) signaling (R-HSA-9705462)
  Other interleukin signaling (R-HSA-449836)

Molecular Interaction Atlas (MIA) of This DTT

2 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Pegfilgrastim	DM7UP8X	Central nervous system neoplasm		Approved	[1]
Tbo-Filgrastim	DML6OE7	Neutropenia	4B00.0	Approved	[2]

9 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Peg-G-CSF	DMBKWAF	Solid tumour/cancer	2A00-2F9Z	Phase 3	[3]
AX-200	DMTAEMB	Cardiovascular disease	BA00-BE2Z	Phase 2	[4]
BLZ-945	DMG1LVA	Amyotrophic lateral sclerosis	8B60.0	Phase 2	[3]
MAXY-G34	DMWLIPJ	Neutropenia	4B00.0	Phase 2	[5]
SBC-014	DMG1VXR	Neutropenia	4B00.0	Phase 2	[6]
AMG 820	DMB6Q19	Solid tumour/cancer	2A00-2F9Z	Phase 1	[7]
MK-6302	DMZUA5C	Neutropenia	4B00.0	Phase 1	[8]
PLX-5622	DMK4PWM	Autoimmune diabetes	5A10	Phase 1	[9]
PLX7486	DM0IVGU	Pancreatic cancer	2C10	Phase 1	[10]

1 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ZD-6003	DMU2F6Q	Solid tumour/cancer	2A00-2F9Z	Terminated	[3]

7 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
AC-710	DMXS72J	Autoimmune diabetes	5A10	Investigative	[3]
AZD-7507	DMLJPDW	Solid tumour/cancer	2A00-2F9Z	Investigative	[3]
CSL-324	DMTN1P2	Inflammation	1A00-CA43.1	Investigative	[3]
G-CSF	DMVFDYU	leukaemia	2A60-2B33	Investigative	[3]
N-(2-morpholinophenyl)-5-nitrofuran-2-carboxamide	DMI4KNB	Discovery agent	N.A.	Investigative	[11]
TG-3003	DMHTEMP	Solid tumour/cancer	2A00-2F9Z	Investigative	[3]
ZP-G-CSF	DM9XFYZ	Neutropenia	4B00.0	Investigative	[3]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Alzheimer's disease	8A00.0	Entorhinal cortex	2.08E-08	0.36	0.96
Colon cancer	2C82	Colon tissue	1.28E-21	0.23	0.77
Breast cancer	2C82	Breast tissue	1.13E-26	0.28	0.61
Acute myelocytic leukaemia	2C82	Bone marrow	4.08E-03	-0.1	-0.17
Glioma	2C82	Brainstem tissue	3.85E-01	-0.53	-1.18
Glioma	2C82	White matter	1.71E-01	-0.21	-0.11
Rheumatoid arthritis	FA20	Synovial tissue	1.02E-01	0.38	1.37

References

• [1] Evidence that the granulocyte colony-stimulating factor (G-CSF) receptor plays a role in the pharmacokinetics of G-CSF and PegG-CSF using a G-CSF-R KO model. Pharmacol Res. 2004 Jul;50(1):55-8.
• [2] Nat Rev Drug Discov. 2013 Feb;12(2):87-90.
• [3] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 1719).
• [4] Granulocyte colony-stimulating factor in patients with acute ischemic stroke: results of the AX200 for Ischemic Stroke trial. Stroke. 2013 Oct;44(10):2681-7.
• [5] Survival efficacy of the PEGylated G-CSFs Maxy-G34 and neulasta in a mouse model of lethal H-ARS, and residual bone marrow damage in treated survivors. Health Phys. 2014 Jan;106(1):21-38.
• [6] A glycosylated recombinant human granulocyte colony stimulating factor produced in a novel protein production system (AVI-014) in healthy subjects: a first-in human, single dose, controlled study. BMC Clin Pharmacol. 2009; 9: 2.
• [7] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [8] Merck ditches biogeneric. Nat Biotechnol. 2010 Jul;28(7):636.
• [9] Microglial Stimulation of Glioblastoma Invasion Involves Epidermal Growth Factor Receptor (EGFR) and Colony Stimulating Factor 1 Receptor (CSF-1R) Signaling. Mol Med. 2012; 18(1): 519-527.
• [10] National Cancer Institute Drug Dictionary (drug id 747694).
• [11] Potent 2'-aminoanilide inhibitors of cFMS as potential anti-inflammatory agents. Bioorg Med Chem Lett. 2007 Nov 15;17(22):6070-4.