Target Information
| Target General Information | Top | |||||
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| Target ID |
T73097
(Former ID: TTDS00442)
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| Target Name |
GMCSFR-alpha (CSF2RA)
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| Synonyms |
GMR; GM-CSFR; GM-CSF-R-alpha; CSF2RA; CDw116; CD116 antigen
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| Gene Name |
CSF2RA
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| Target Type |
Successful target
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[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Transplanted organ/tissue [ICD-11: QB63] | |||||
| 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.
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| BioChemical Class |
Type I cytokine receptor family
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| UniProt ID | ||||||
| Sequence |
MLLLVTSLLLCELPHPAFLLIPEKSDLRTVAPASSLNVRFDSRTMNLSWDCQENTTFSKC
FLTDKKNRVVEPRLSNNECSCTFREICLHEGVTFEVHVNTSQRGFQQKLLYPNSGREGTA AQNFSCFIYNADLMNCTWARGPTAPRDVQYFLYIRNSKRRREIRCPYYIQDSGTHVGCHL DNLSGLTSRNYFLVNGTSREIGIQFFDSLLDTKKIERFNPPSNVTVRCNTTHCLVRWKQP RTYQKLSYLDFQYQLDVHRKNTQPGTENLLINVSGDLENRYNFPSSEPRAKHSVKIRAAD VRILNWSSWSEAIEFGSDDGNLGSVYIYVLLIVGTLVCGIVLGFLFKRFLRIQRLFPPVP QIKDKLNDNHEVEDEIIWEEFTPEEGKGYREEVLTVKEIT Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| Drugs and Modes of Action | Top | |||||
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| Approved Drug(s) | [+] 1 Approved Drugs | + | ||||
| 1 | Sargramostim | Drug Info | Approved | Bone marrow transplantation | [2], [3] | |
| Clinical Trial Drug(s) | [+] 10 Clinical Trial Drugs | + | ||||
| 1 | B-cell lymphoma vaccine | Drug Info | Preregistration | Follicular lymphoma | [4] | |
| 2 | Molgramostim | Drug Info | Phase 3 | Autoimmune pulmonary alveolar proteinosis | [5] | |
| 3 | Pixykine | Drug Info | Phase 3 | Human immunodeficiency virus infection | [6] | |
| 4 | AFTVac | Drug Info | Phase 2 | Glioblastoma multiforme | [7] | |
| 5 | GM-CSF cancer vaccine | Drug Info | Phase 2 | Solid tumour/cancer | [8] | |
| 6 | Leukemia cancer vaccine | Drug Info | Phase 2 | Acute myeloid leukaemia | [9] | |
| 7 | Mavrilimumab | Drug Info | Phase 2 | Rheumatoid arthritis | [10], [11] | |
| 8 | Myeloma cancer vaccine | Drug Info | Phase 2 | Multiple myeloma | [9] | |
| 9 | MOR-103 | Drug Info | Phase 1/2 | Multiple sclerosis | [12] | |
| 10 | KH-901 | Drug Info | Phase 1 | Solid tumour/cancer | [13] | |
| Discontinued Drug(s) | [+] 1 Discontinued Drugs | + | ||||
| 1 | SDZ-62-826 | Drug Info | Terminated | Solid tumour/cancer | [14] | |
| Mode of Action | [+] 4 Modes of Action | + | ||||
| Binder | [+] 1 Binder drugs | + | ||||
| 1 | Sargramostim | Drug Info | [1], [15] | |||
| Agonist | [+] 1 Agonist drugs | + | ||||
| 1 | Molgramostim | Drug Info | [17] | |||
| Modulator | [+] 2 Modulator drugs | + | ||||
| 1 | Pixykine | Drug Info | [18] | |||
| 2 | SDZ-62-826 | Drug Info | [19] | |||
| Stimulator | [+] 1 Stimulator drugs | + | ||||
| 1 | BBT-007 | Drug Info | [19] | |||
| Cell-based Target Expression Variations | Top | |||||
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| Cell-based Target Expression Variations | ||||||
| Different Human System Profiles of Target | Top |
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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
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| Protein Name | Pfam ID | Percentage of Identity (%) | E value |
|---|---|---|---|
| Prolactin receptor (PRLR) | 23.675 (67/283) | 6.01E-11 |
| KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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| Cytokine-cytokine receptor interaction | hsa04060 | Affiliated Target |
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| Class: Environmental Information Processing => Signaling molecules and interaction | Pathway Hierarchy | ||
| JAK-STAT signaling pathway | hsa04630 | Affiliated Target |
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| Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy | ||
| Hematopoietic cell lineage | hsa04640 | Affiliated Target |
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| Class: Organismal Systems => Immune system | Pathway Hierarchy | ||
| Degree | 4 | Degree centrality | 4.30E-04 | Betweenness centrality | 5.94E-06 |
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| Closeness centrality | 2.12E-01 | Radiality | 1.37E+01 | Clustering coefficient | 5.00E-01 |
| Neighborhood connectivity | 4.13E+01 | Topological coefficient | 2.93E-01 | Eccentricity | 12 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Target Regulators | Top | |||||
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| Target-interacting Proteins | ||||||
| Target Profiles in Patients | Top | |||||
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| Target Expression Profile (TEP) | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| KEGG Pathway | [+] 4 KEGG Pathways | + | ||||
| 1 | Cytokine-cytokine receptor interaction | |||||
| 2 | Jak-STAT signaling pathway | |||||
| 3 | Hematopoietic cell lineage | |||||
| 4 | Pathways in cancer | |||||
| NetPath Pathway | [+] 2 NetPath Pathways | + | ||||
| 1 | IL3 Signaling Pathway | |||||
| 2 | RANKL Signaling Pathway | |||||
| PID Pathway | [+] 2 PID Pathways | + | ||||
| 1 | GMCSF-mediated signaling events | |||||
| 2 | Alpha9 beta1 integrin signaling events | |||||
| Reactome | [+] 6 Reactome Pathways | + | ||||
| 1 | GPVI-mediated activation cascade | |||||
| 2 | G beta:gamma signalling through PI3Kgamma | |||||
| 3 | Interleukin-3, 5 and GM-CSF signaling | |||||
| 4 | RAF/MAP kinase cascade | |||||
| 5 | Surfactant metabolism | |||||
| 6 | Interleukin receptor SHC signaling | |||||
| WikiPathways | [+] 2 WikiPathways | + | ||||
| 1 | Interleukin-2 signaling | |||||
| 2 | Interleukin-3, 5 and GM-CSF signaling | |||||
| References | Top | |||||
|---|---|---|---|---|---|---|
| REF 1 | Stem cell transplantation and hematopoietic growth factors. Curr Hematol Rep. 2002 Nov;1(2):103-9. | |||||
| REF 2 | 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. (Ligand id: 7905). | |||||
| REF 3 | Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77. | |||||
| REF 4 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800006688) | |||||
| REF 5 | ClinicalTrials.gov (NCT04544293) Clinical Trial of Inhaled Molgramostim Nebulizer Solution in Autoimmune Pulmonary Alveolar Proteinosis (aPAP) (IMPALA-2). U.S. National Institutes of Health. | |||||
| REF 6 | ClinicalTrials.gov (NCT00001338) A Prospective, Randomized, Phase III Trial of FLAC (5-Fluorouracil, Leucovorin, Adriamycin, Cytoxan) Chemotherapy With GM-CSF (Granulocyte-Macrophage Colony-Stimulating Factor) Versus PIXY 321 in Advanced Breast Cancer. U.S. National Institutes of Health. | |||||
| REF 7 | 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. | |||||
| REF 8 | A safety and efficacy trial of lethally irradiated allogeneic pancreatic tumor cells transfected with the GM-CSF gene in combination with adjuvant chemoradiotherapy for the treatment of adenocarcinoma of the pancreas. Journal of Clinical Oncology, Vol 25, No 18S (June 20 Supplement), 2007: 3010. | |||||
| REF 9 | ClinicalTrials.gov (NCT02243371) GVAX Pancreas Vaccine (With CY) and CRS-207 With or Without Nivolumab. U.S. National Institutes of Health. | |||||
| REF 10 | 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. (Ligand id: 7785). | |||||
| REF 11 | Clinical pipeline report, company report or official report of MedImmune (2011). | |||||
| REF 12 | ClinicalTrials.gov (NCT01023256) Safety and Preliminary Efficacy of MOR103 in Patients With Active Rheumatoid Arthritis. U.S. National Institutes of Health. | |||||
| REF 13 | A Phase I study of KH901, a conditionally replicating granulocyte-macrophage colony-stimulating factor: armed oncolytic adenovirus for the treatmen... Cancer Biol Ther. 2009 Apr;8(8):676-82. | |||||
| REF 14 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800004355) | |||||
| REF 15 | Economic evaluation of filgrastim, sargramostim, and sequential sargramostim and filgrastim after myelosuppressive chemotherapy. Bone Marrow Transplant. 2002 Jan;29(2):159-64. | |||||
| REF 16 | Idiotypevaccinetherapy (BiovaxID) infollicularlymphomain first complete remission: Phase III clinical trial results, Journal of Clinical Oncology, Vol 27, No 18S (June 20 Supplement), 2009: 2. | |||||
| REF 17 | Clinical pipeline report, company report or official report of gensci-china. | |||||
| REF 18 | 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. | |||||
| REF 19 | 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). | |||||
| REF 20 | 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. | |||||
| REF 21 | 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. | |||||
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