Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTDN3LF)

• DTT Name: Nerve growth factor (NGF)
• Synonyms: NGFB; Beta-nerve growth factor; Beta-NGF
• Gene Name: NGF
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Growth factor
• UniProt ID: NGF_HUMAN
• TTD ID: T85670
• Sequence:
  MSMLFYTLITAFLIGIQAEPHSESNVPAGHTIPQAHWTKLQHSLDTALRRARSAPAAAIA
  ARVAGQTRNITVDPRLFKKRRLRSPRVLFSTQPPREAADTQDLDFEVGGAAPFNRTHRSK
  RSSSHPIFHRGEFSVCDSVSVWVGDKTTATDIKGKEVMVLGEVNINNSVFKQYFFETKCR
  DPNPVDSGCRGIDSKHWNSYCTTTHTFVKALTMDGKQAAWRFIRIDTACVCVLSRKAVRR
  A
• 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).
• KEGG Pathway:
  MAPK signaling pathway (hsa04010)
  Ras signaling pathway (hsa04014)
  Rap1 signaling pathway (hsa04015)
  PI3K-Akt signaling pathway (hsa04151)
  Apoptosis (hsa04210)
  Neurotrophin signaling pathway (hsa04722)
  Inflammatory mediator regulation of TRP channels (hsa04750)
• Reactome Pathway:
  ARMS-mediated activation (R-HSA-170984)
  NRAGE signals death through JNK (R-HSA-193648)
  p75NTR negatively regulates cell cycle via SC1 (R-HSA-193670)
  PI3K/AKT activation (R-HSA-198203)
  NADE modulates death signalling (R-HSA-205025)
  NRIF signals cell death from the nucleus (R-HSA-205043)
  p75NTR recruits signalling complexes (R-HSA-209543)
  NF-kB is activated and signals survival (R-HSA-209560)
  Axonal growth stimulation (R-HSA-209563)
  Frs2-mediated activation (R-HSA-170968)

Molecular Interaction Atlas (MIA) of This DTT

8 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Fasinumab	DM5PRLA	Chronic low back pain	MG30.02	Phase 3	[2]
Tanezumab	DMJKWMA	Cancer related pain	MG30	Phase 3	[2]
SAR164877	DMOJLCV	Pain	MG30-MG3Z	Phase 2/3	[1]
CERE-110	DMNW5I9	Alzheimer disease	8A20	Phase 2	[3]
CXB-909	DMUGMFN	Neurodegenerative disorder	8A20-8A23	Phase 1/2	[4]
ABT-110	DM1F50I	Chronic pain	MG30	Phase 1	[1]
MEDI-578	DMPW21Z	Pain	MG30-MG3Z	Phase 1	[1]
NsG-0202	DM1ITDN	Alzheimer disease	8A20	Phase 1	[4]

1 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Nerve growth factor	DMHYQ8K	Alzheimer disease	8A20	Terminated	[5]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Alzheimer's disease	8A00.0	Entorhinal cortex	5.57E-02	-0.06	-0.31

References

• [1] Fate of novel painkiller mAbs hangs in balance.Nat Biotechnol.2011 Mar;29(3):173-4.
• [2] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [3] 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.
• [4] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
• [5] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.