Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT6MP2Z)

• DTT Name: GMCSFR-alpha (CSF2RA)
• Synonyms: GMR; GM-CSFR; GM-CSF-R-alpha; CSF2RA; CDw116; CD116 antigen
• Gene Name: CSF2RA
• DTT Type: Successful target; [1]
• BioChemical Class: Type I cytokine receptor family
• UniProt ID: CSF2R_HUMAN
• TTD ID: T73097
• Sequence:
  MLLLVTSLLLCELPHPAFLLIPEKSDLRTVAPASSLNVRFDSRTMNLSWDCQENTTFSKC
  FLTDKKNRVVEPRLSNNECSCTFREICLHEGVTFEVHVNTSQRGFQQKLLYPNSGREGTA
  AQNFSCFIYNADLMNCTWARGPTAPRDVQYFLYIRNSKRRREIRCPYYIQDSGTHVGCHL
  DNLSGLTSRNYFLVNGTSREIGIQFFDSLLDTKKIERFNPPSNVTVRCNTTHCLVRWKQP
  RTYQKLSYLDFQYQLDVHRKNTQPGTENLLINVSGDLENRYNFPSSEPRAKHSVKIRAAD
  VRILNWSSWSEAIEFGSDDGNLGSVYIYVLLIVGTLVCGIVLGFLFKRFLRIQRLFPPVP
  QIKDKLNDNHEVEDEIIWEEFTPEEGKGYREEVLTVKEIT
• Function: Low affinity receptor for granulocyte-macrophage colony- stimulating factor. Transduces a signal that results in the proliferation, differentiation, and functional activation of hematopoietic cells.
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  Jak-STAT signaling pathway (hsa04630)
  Hematopoietic cell lineage (hsa04640)
  Pathways in cancer (hsa05200)
• Reactome Pathway:
  G beta (R-HSA-392451)
  Interleukin-3, 5 and GM-CSF signaling (R-HSA-512988)
  RAF/MAP kinase cascade (R-HSA-5673001)
  Surfactant metabolism (R-HSA-5683826)
  Interleukin receptor SHC signaling (R-HSA-912526)
  GPVI-mediated activation cascade (R-HSA-114604)

Molecular Interaction Atlas (MIA) of This DTT

1 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Sargramostim	DMY0M8J	Bone marrow transplantation	QB63.6	Approved	[1]

10 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
B-cell lymphoma vaccine	DMBRFUQ	Follicular lymphoma	2A80	Preregistration	[2]
Molgramostim	DM2TNJ1	Autoimmune pulmonary alveolar proteinosis	CB04.31	Phase 3	[3]
Pixykine	DMCA6BW	Human immunodeficiency virus infection	1C62	Phase 3	[4]
AFTVac	DMD3XMG	Glioblastoma multiforme	2A00.0	Phase 2	[5]
GM-CSF cancer vaccine	DML6PO5	Solid tumour/cancer	2A00-2F9Z	Phase 2	[6]
Leukemia cancer vaccine	DMIFGLY	Acute myeloid leukaemia	2A60	Phase 2	[6]
Mavrilimumab	DMMVFRC	Rheumatoid arthritis	FA20	Phase 2	[7]
Myeloma cancer vaccine	DMO1XUK	Multiple myeloma	2A83	Phase 2	[6]
MOR-103	DMXVIQN	Multiple sclerosis	8A40	Phase 1/2	[8]
KH-901	DMR14VE	Solid tumour/cancer	2A00-2F9Z	Phase 1	[9]

1 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
SDZ-62-826	DMAT657	Solid tumour/cancer	2A00-2F9Z	Terminated	[6]

1 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
BBT-007	DMT0X6Q	Neutropenia	4B00.0	Investigative	[6]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Acute myelocytic leukaemia	2C82	Bone marrow	1.10E-05	-0.49	-0.88
Multiple myeloma	2C82	Bone marrow	3.76E-03	0.14	1.25
Glioma	2C82	Brainstem tissue	7.80E-01	-0.13	-0.28
Glioma	2C82	White matter	1.96E-01	0.44	0.38
Rheumatoid arthritis	FA20	Synovial tissue	8.42E-01	0.16	0.53
Rectal cancer	2C82	Rectal colon tissue	4.48E-03	-0.43	-2.15

References

• [1] Stem cell transplantation and hematopoietic growth factors. Curr Hematol Rep. 2002 Nov;1(2):103-9.
• [2] Idiotypevaccinetherapy (BiovaxID) infollicularlymphomain first complete remission: Phase III clinical trial results, Journal of Clinical Oncology, Vol 27, No 18S (June 20 Supplement), 2009: 2.
• [3] Clinical pipeline report, company report or official report of gensci-china.
• [4] Phase I/II trial of PIXY321 (granulocyte-macrophage colony stimulating factor/interleukin-3 fusion protein) for treatment of inherited and acquired... Br J Haematol. 1998 Nov;103(2):304-7.
• [5] Phase II randomized trial of autologous formalin-fixed tumor vaccine for postsurgical recurrence of hepatocellular carcinoma. Clin Cancer Res. 2004 Mar 1;10(5):1574-9.
• [6] 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: 1707).
• [7] Clinical pipeline report, company report or official report of MedImmune (2011).
• [8] MOR103, a human monoclonal antibody to granulocyte-macrophage colony-stimulating factor, in the treatment of patients with moderate rheumatoid arthritis: results of a phase Ib/IIa randomised, double-blind, placebo-controlled, dose-escalation trial. Ann Rheum Dis. 2015 Jun;74(6):1058-64.
• [9] Effects of KH901, a tumor-specific oncolytic recombinant adenovirus, on antitumor and expressing GM-CSF in xenograft tumor models. Sichuan Da Xue Xue Bao Yi Xue Ban. 2007 Jun;38(3):386-90.