Target Information
| Target General Information | Top | |||||
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| Target ID |
T85670
(Former ID: TTDI02219)
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| Target Name |
Nerve growth factor (NGF)
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| Synonyms |
NGFB; Beta-nerve growth factor; Beta-NGF
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| Gene Name |
NGF
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| Target Type |
Clinical trial target
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[1] | ||||
| Disease | [+] 4 Target-related Diseases | + | ||||
| 1 | Chronic pain [ICD-11: MG30] | |||||
| 2 | General pain disorder [ICD-11: 8E43] | |||||
| 3 | Osteoarthritis [ICD-11: FA00-FA05] | |||||
| 4 | Pain [ICD-11: MG30-MG3Z] | |||||
| Function |
Nerve growth factor is important for the development and maintenance of the sympathetic and sensory nervous systems. Extracellular ligand for the NTRK1 and NGFR receptors, activates cellular signaling cascades to regulate neuronal proliferation, differentiation and survival (Probable). The immature NGF precursor (proNGF) functions as ligand for the heterodimeric receptor formed by SORCS2 and NGFR, and activates cellular signaling cascades that lead to inactivation of RAC1 and/or RAC2, reorganization of the actin cytoskeleton and neuronal growth cone collapse. In contrast to mature NGF, the precursor form (proNGF) promotes neuronal apoptosis (in vitro) (By similarity). Inhibits metalloproteinase-dependent proteolysis of platelet glycoprotein VI. Binds lysophosphatidylinositol and lysophosphatidylserine between the two chains of the homodimer. The lipid-bound form promotes histamine relase from mast cells, contrary to the lipid-free form (By similarity).
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| BioChemical Class |
Growth factor
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| UniProt ID | ||||||
| Sequence |
MSMLFYTLITAFLIGIQAEPHSESNVPAGHTIPQAHWTKLQHSLDTALRRARSAPAAAIA
ARVAGQTRNITVDPRLFKKRRLRSPRVLFSTQPPREAADTQDLDFEVGGAAPFNRTHRSK RSSSHPIFHRGEFSVCDSVSVWVGDKTTATDIKGKEVMVLGEVNINNSVFKQYFFETKCR DPNPVDSGCRGIDSKHWNSYCTTTHTFVKALTMDGKQAAWRFIRIDTACVCVLSRKAVRR A Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| HIT2.0 ID | T83QHM | |||||
| Drugs and Modes of Action | Top | |||||
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| Clinical Trial Drug(s) | [+] 7 Clinical Trial Drugs | + | ||||
| 1 | Fasinumab | Drug Info | Phase 3 | Neuropathic pain | [2] | |
| 2 | Tanezumab | Drug Info | Phase 3 | Neuropathic pain | [2] | |
| 3 | SAR164877 | Drug Info | Phase 2/3 | Pain | [3] | |
| 4 | CERE-110 | Drug Info | Phase 2 | Alzheimer disease | [4] | |
| 5 | ABT-110 | Drug Info | Phase 1 | Chronic pain | [6] | |
| 6 | MEDI-578 | Drug Info | Phase 1 | Pain | [7] | |
| 7 | NsG-0202 | Drug Info | Phase 1 | Alzheimer disease | [8] | |
| Discontinued Drug(s) | [+] 1 Discontinued Drugs | + | ||||
| 1 | Nerve growth factor | Drug Info | Terminated | Alzheimer disease | [9] | |
| Mode of Action | [+] 2 Modes of Action | + | ||||
| Inhibitor | [+] 2 Inhibitor drugs | + | ||||
| 1 | Fasinumab | Drug Info | [2] | |||
| 2 | Tanezumab | Drug Info | [2] | |||
| Modulator | [+] 6 Modulator drugs | + | ||||
| 1 | SAR164877 | Drug Info | [1] | |||
| 2 | CERE-110 | Drug Info | [10] | |||
| 3 | ABT-110 | Drug Info | [1], [11] | |||
| 4 | MEDI-578 | Drug Info | [1] | |||
| 5 | NsG-0202 | Drug Info | [12] | |||
| 6 | Nerve growth factor | Drug Info | [13] | |||
| 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 Tissue Distribution
of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.
The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects
(Nat Rev Drug Discov, 20: 64-81, 2021).
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 Tissue Distribution
Human Pathway Affiliation
Biological Network Descriptors
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There is no similarity protein (E value < 0.005) for this target
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Note:
If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.
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| KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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| MAPK signaling pathway | hsa04010 | Affiliated Target |
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| Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy | ||
| Ras signaling pathway | hsa04014 | Affiliated Target |
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| Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy | ||
| Rap1 signaling pathway | hsa04015 | Affiliated Target |
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| Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy | ||
| Calcium signaling pathway | hsa04020 | Affiliated Target |
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| Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy | ||
| Cytokine-cytokine receptor interaction | hsa04060 | Affiliated Target |
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| Class: Environmental Information Processing => Signaling molecules and interaction | Pathway Hierarchy | ||
| PI3K-Akt signaling pathway | hsa04151 | Affiliated Target |
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| Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy | ||
| Apoptosis | hsa04210 | Affiliated Target |
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| Class: Cellular Processes => Cell growth and death | Pathway Hierarchy | ||
| Neurotrophin signaling pathway | hsa04722 | Affiliated Target |
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| Class: Organismal Systems => Nervous system | Pathway Hierarchy | ||
| Inflammatory mediator regulation of TRP channels | hsa04750 | Affiliated Target |
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| Class: Organismal Systems => Sensory system | Pathway Hierarchy | ||
| Click to Show/Hide the Information of Affiliated Human Pathways | |||
| Degree | 17 | Degree centrality | 1.83E-03 | Betweenness centrality | 1.03E-03 |
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| Closeness centrality | 2.44E-01 | Radiality | 1.43E+01 | Clustering coefficient | 2.57E-01 |
| Neighborhood connectivity | 5.13E+01 | Topological coefficient | 9.66E-02 | Eccentricity | 11 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Target Regulators | Top | |||||
|---|---|---|---|---|---|---|
| Target-interacting Proteins | ||||||
| Target Profiles in Patients | Top | |||||
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| Target Expression Profile (TEP) | ||||||
| References | Top | |||||
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| REF 1 | Fate of novel painkiller mAbs hangs in balance.Nat Biotechnol.2011 Mar;29(3):173-4. | |||||
| REF 2 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 3 | ClinicalTrials.gov (NCT02447276) Study of REGN475 in Patients With Pain Due to Osteoarthritis of the Knee or Hip. U.S. National Institutes of Health. | |||||
| REF 4 | ClinicalTrials.gov (NCT00876863) Randomized, Controlled Study Evaluating CERE-110 in Subjects With Mild to Moderate Alzheimer's Disease. U.S. National Institutes of Health. | |||||
| REF 5 | ClinicalTrials.gov (NCT01505907) Pharmacokinetic Study of CXB909 in Healthy Male Subjects. U.S. National Institutes of Health. | |||||
| REF 6 | ClinicalTrials.gov (NCT00941746) Safety and Tolerability of PG110 in Patients With Knee Osteoarthritis Pain. U.S. National Institutes of Health. | |||||
| REF 7 | Clinical pipeline report, company report or official report of MedImmune (2011). | |||||
| REF 8 | ClinicalTrials.gov (NCT01163825) Encapsulated Cell Biodelivery of Nerve Growth Factor to Alzheimer Disease Patients. U.S. National Institutes of Health. | |||||
| REF 9 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000658) | |||||
| REF 10 | CERE-110, an adeno-associated virus-based gene delivery vector expressing human nerve growth factor for the treatment of Alzheimer's disease. Curr Opin Mol Ther. 2010 Apr;12(2):240-7. | |||||
| REF 11 | Targeting nerve growth factor (NGF) for pain management: what does the future hold for NGF antagonists Drugs.2014 Apr;74(6):619-26. | |||||
| REF 12 | Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41. | |||||
| REF 13 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. | |||||
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