Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTNYZG2)

• DTT Name: Granulocyte-macrophage colony-stimulating factor (CSF2)
• Synonyms: Sargramostim; Molgramostin; GM-CSF; Colony-stimulating factor; CSF2; CSF
• Gene Name: CSF2
• DTT Type: Successful target; [1]
• BioChemical Class: Growth factor
• UniProt ID: CSF2_HUMAN
• TTD ID: T74002
• Sequence:
  MWLQSLLLLGTVACSISAPARSPSPSTQPWEHVNAIQEARRLLNLSRDTAAEMNETVEVI
  SEMFDLQEPTCLQTRLELYKQGLRGSLTKLKGPLTMMASHYKQHCPPTPETSCATQIITF
  ESFKENLKDFLLVIPFDCWEPVQE
• Function: Cytokine that stimulates the growth and differentiation of hematopoietic precursor cells from various lineages, including granulocytes, macrophages, eosinophils and erythrocytes.
• KEGG Pathway:
  Cytokine-cytokine receptor interaction (hsa04060)
  Jak-STAT signaling pathway (hsa04630)
  Hematopoietic cell lineage (hsa04640)
  Natural killer cell mediated cytotoxicity (hsa04650)
  T cell receptor signaling pathway (hsa04660)
  Fc epsilon RI signaling pathway (hsa04664)
  TNF signaling pathway (hsa04668)
  Salmonella infection (hsa05132)
  Amoebiasis (hsa05146)
  HTLV-I infection (hsa05166)
  Transcriptional misregulation in cancer (hsa05202)
  Rheumatoid arthritis (hsa05323)
• Reactome Pathway:
  G beta (R-HSA-392451)
  Interleukin-3, 5 and GM-CSF signaling (R-HSA-512988)
  RAF/MAP kinase cascade (R-HSA-5673001)
  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
Talimogene Laherparepvec	DMKBW5C	Melanoma	2C30	Approved	[1]

11 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
JX-594	DM5WCV4	Hepatocellular carcinoma	2C12.02	Phase 3	[2]
Cabiralizumab	DMGE058	Pancreatic cancer	2C10	Phase 2	[3]
GSK3196165	DMEXKF4	Rheumatoid arthritis	FA20	Phase 2	[4]
KB-003	DM74KIM	Severe asthma	CA23	Phase 2	[5]
KB002/003	DM60G5O	Rheumatoid arthritis	FA20	Phase 2	[6]
Mavrilimumab	DMMVFRC	Rheumatoid arthritis	FA20	Phase 2	[4]
MT203	DM7I0MT	Plaque psoriasis	EA90.0	Phase 2	[7]
Autologous melanoma cell vaccine	DMARYFK	Solid tumour/cancer	2A00-2F9Z	Phase 1	[6]
CDNA vaccine	DM8DWOL	Prostate cancer	2C82.0	Phase 1	[6]
CGTG-102	DMAY8I4	Solid tumour/cancer	2A00-2F9Z	Phase 1	[8]
MORAb-022	DMM7TBO	Autoimmune diabetes	5A10	Phase 1	[9]

1 Drugs in Phase 3 Trial Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Lenzilumab	DMSRIT4	Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 3 Trial	[3]

1 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
RPK-739	DMUCP8K	Solid tumour/cancer	2A00-2F9Z	Terminated	[1]

1 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
human monoclonal antibodies (GM-CSF)	DMFV5UL	Discovery agent	N.A.	Investigative	[10]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Ovarian cancer	2C82	Ovarian tissue	2.36E-01	-0.06	-0.26
Asthma	CA23	Nasal and bronchial airway	8.82E-01	-0.01	-0.03
Liver cancer	2C82	Liver tissue	2.22E-06	-0.16	-0.88
Bladder cancer	2C82	Bladder tissue	4.07E-03	0.26	1.2
Prostate cancer	2C82	Prostate	9.87E-03	-0.45	-0.99
Rheumatoid arthritis	FA20	Synovial tissue	6.52E-04	-0.35	-2.33
Melanoma	2C82	Skin	6.60E-01	0.09	0.2

References

• [1] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [2] Systemic armed oncolytic and immunologic therapy for cancer with JX-594, a targeted poxvirus expressing GM-CSF. Mol Ther. 2006 Sep;14(3):361-70.
• [3] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [4] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [5] US patent application no. 2010,0158,905, Combination therapy of arthritis with tranilast.
• [6] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
• [7] GM-CSF as a target in inflammatory/autoimmune disease: current evidence and future therapeutic potential. Expert Rev Clin Immunol. 2015 Apr;11(4):457-65.
• [8] Serotype chimeric oncolytic adenovirus coding for GM-CSF for treatment of sarcoma in rodents and humans. Int J Cancer. 2014 Aug 1;135(3):720-30.
• [9] Clinical pipeline report, company report or official report of Morphotek.
• [10] The ChEMBL database in 2017. Nucleic Acids Res. 2017 Jan 4;45(D1):D945-D954.