Target Information

Target General Information

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Target ID

T94514

Target Name

HUMAN colony-stimulating factor (GM-CSF)

Synonyms

Sargramostim; Molgramostin; GM-CSF; Colony-stimulating factor; CSF2; CSF

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Gene Name

CSF2

Disease

[+] 2 Target-related Diseases

COVID-19 [ICD-11: 1D6Y]

Rheumatoid arthritis [ICD-11: FA20]

Function

Cytokine that stimulates the growth and differentiation of hematopoietic precursor cells from various lineages, including granulocytes, macrophages, eosinophils and erythrocytes.

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BioChemical Class

Growth factor

UniProt ID

CSF2_HUMAN

Sequence

MWLQSLLLLGTVACSISAPARSPSPSTQPWEHVNAIQEARRLLNLSRDTAAEMNETVEVI
SEMFDLQEPTCLQTRLELYKQGLRGSLTKLKGPLTMMASHYKQHCPPTPETSCATQIITF
ESFKENLKDFLLVIPFDCWEPVQE

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3D Structure

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PDB

Drugs and Modes of Action

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Drugs in Phase 3 Trial

[+] 1

Lenzilumab

Drug Info

Phase 3

Coronavirus Disease 2019 (COVID-19)

[2]

Drugs in Phase 2 Trial

[+] 1

Otilimab

Drug Info

Phase 3

Rheumatoid arthritis

[3]

Drugs in Phase 1 Trial

[+] 1

TJ003234

Drug Info

Phase 1/2

Coronavirus Disease 2019 (COVID-19)

[2]

Mode of Action

[+] 1 Modes of Action

Inhibitor

[+] 3 Inhibitor drugs

Lenzilumab

Drug Info

[1], [4]

Otilimab

Drug Info

[1], [5]

TJ003234

Drug Info

[1], [6]

Cell-based Target Expression Variations

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Cell-based Target Expression Variations

Cell-based Target Expression Variations Info

Different Human System Profiles of Target	Top
Human Similarity Proteins of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target. A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs (Brief Bioinform, 21: 649-662, 2020). Human Pathway Affiliation of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function. Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes (Pharmacol Rev, 58: 259-279, 2006). Biological Network Descriptors of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database. The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information (Front Pharmacol, 9, 1245, 2018; Curr Opin Struct Biol. 44:134-142, 2017). Human Similarity Proteins Human Pathway Affiliation Biological Network Descriptors

Different Human System Profiles of Target

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Human Similarity Proteins of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.

A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs (Brief Bioinform, 21: 649-662, 2020).

Human Pathway Affiliation of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.

Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes (Pharmacol Rev, 58: 259-279, 2006).

Biological Network Descriptors of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.

The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information (Front Pharmacol, 9, 1245, 2018; Curr Opin Struct Biol. 44:134-142, 2017).

Human Similarity Proteins

Human Pathway Affiliation

Biological Network Descriptors

There is no similarity protein (E value < 0.005) for this target

KEGG Pathway	Pathway ID	Affiliated Target
Cytokine-cytokine receptor interaction	hsa04060	Affiliated Target
Class: Environmental Information Processing => Signaling molecules and interaction	Pathway Hierarchy
JAK-STAT signaling pathway	hsa04630	Affiliated Target
Class: Environmental Information Processing => Signal transduction	Pathway Hierarchy
Hematopoietic cell lineage	hsa04640	Affiliated Target
Class: Organismal Systems => Immune system	Pathway Hierarchy
Natural killer cell mediated cytotoxicity	hsa04650	Affiliated Target
Class: Organismal Systems => Immune system	Pathway Hierarchy
IL-17 signaling pathway	hsa04657	Affiliated Target
Class: Organismal Systems => Immune system	Pathway Hierarchy
T cell receptor signaling pathway	hsa04660	Affiliated Target
Class: Organismal Systems => Immune system	Pathway Hierarchy
Fc epsilon RI signaling pathway	hsa04664	Affiliated Target
Class: Organismal Systems => Immune system	Pathway Hierarchy
TNF signaling pathway	hsa04668	Affiliated Target
Class: Environmental Information Processing => Signal transduction	Pathway Hierarchy
Click to Show/Hide the Information of Affiliated Human Pathways

Degree	31	Degree centrality	3.33E-03	Betweenness centrality	5.65E-04
Closeness centrality	2.33E-01	Radiality	1.41E+01	Clustering coefficient	3.57E-01
Neighborhood connectivity	3.43E+01	Topological coefficient	8.56E-02	Eccentricity	11
Download	Click to Download the Full PPI Network of This Target

References

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REF 1

The anti-viral facet of anti-rheumatic drugs: Lessons from COVID-19. J Autoimmun. 2020 Apr 17:102468.

REF 2

ClinicalTrials.gov (NCT04351152) Phase 3 Study to Evaluate Efficacy and Safety of Lenzilumab in Hospitalized Patients With COVID-19 Pneumonia. U.S. National Institutes of Health.

REF 3

ClinicalTrials.gov (NCT04333147) Long-term Safety and Efficacy of GSK3196165 (Otilimab) in the Treatment of Rheumatoid Arthritis (RA). U.S. National Institutes of Health.

REF 4

Learn how Lenzilumab may reduce serious or fatal outcomes in COVID-19 patients

REF 5

GSK's official website (GSK3196165 otilimab)

REF 6

I-Mab Announces IND Clearance from FDA for TJM2 to Treat Cytokine Release Syndrome (CRS) Associated with Severe Coronavirus Disease 19 (COVID-19)

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