Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT2IZ4K)

• DTT Name: Fibroblast growth factor-23 (FGF23)
• Synonyms: Tumor-derived hypophosphatemia-inducing factor; Phosphatonin; HYPF; Fibroblast growth factor 23; FGF-23
• Gene Name: FGF23
• DTT Type: Successful target; [1]
• BioChemical Class: Growth factor
• UniProt ID: FGF23_HUMAN
• TTD ID: T14853
• Sequence:
  MLGARLRLWVCALCSVCSMSVLRAYPNASPLLGSSWGGLIHLYTATARNSYHLQIHKNGH
  VDGAPHQTIYSALMIRSEDAGFVVITGVMSRRYLCMDFRGNIFGSHYFDPENCRFQHQTL
  ENGYDVYHSPQYHFLVSLGRAKRAFLPGMNPPPYSQFLSRRNEIPLIHFNTPIPRRHTRS
  AEDDSERDPLNVLKPRARMTPAPASCSQELPSAEDNSPMASDPLGVVRGGRVNTHAGGTG
  PEGCRPFAKFI
• Function: Regulator of phosphate homeostasis. Inhibits renal tubular phosphate transport by reducing SLC34A1 levels. Upregulates EGR1 expression in the presence of KL (By similarity). Acts directly on the parathyroid to decrease PTH secretion (By similarity). Regulator of vitamin-D metabolism. Negatively regulates osteoblast differentiation and matrix mineralization.
• KEGG Pathway:
  MAPK signaling pathway (hsa04010)
  Ras signaling pathway (hsa04014)
  Rap1 signaling pathway (hsa04015)
  Calcium signaling pathway (hsa04020)
  PI3K-Akt signaling pathway (hsa04151)
  Regulation of actin cytoskeleton (hsa04810)
  Parathyroid hormone synthesis, secretion and action (hsa04928)
  Pathways in cancer (hsa05200)
  Melanoma (hsa05218)
  Breast cancer (hsa05224)
  Gastric cancer (hsa05226)
• Reactome Pathway:
  PIP3 activates AKT signaling (R-HSA-1257604)
  Signaling by activated point mutants of FGFR1 (R-HSA-1839122)
  Signaling by activated point mutants of FGFR3 (R-HSA-1839130)
  FGFR4 ligand binding and activation (R-HSA-190322)
  FGFR3c ligand binding and activation (R-HSA-190372)
  FGFR1c ligand binding and activation (R-HSA-190373)
  FGFR1c and Klotho ligand binding and activation (R-HSA-190374)
  FGFR2c ligand binding and activation (R-HSA-190375)
  Activated point mutants of FGFR2 (R-HSA-2033519)
  Constitutive Signaling by Aberrant PI3K in Cancer (R-HSA-2219530)
  Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) (R-HSA-381426)
  Phospholipase C-mediated cascade (R-HSA-5654219)
  Phospholipase C-mediated cascade, FGFR2 (R-HSA-5654221)
  Phospholipase C-mediated cascade, FGFR3 (R-HSA-5654227)
  Phospholipase C-mediated cascade, FGFR4 (R-HSA-5654228)
  Downstream signaling of activated FGFR1 (R-HSA-5654687)
  SHC-mediated cascade (R-HSA-5654688)
  PI-3K cascade (R-HSA-5654689)
  FRS-mediated FGFR1 signaling (R-HSA-5654693)
  PI-3K cascade (R-HSA-5654695)
  SHC-mediated cascade (R-HSA-5654699)
  FRS-mediated FGFR2 signaling (R-HSA-5654700)
  SHC-mediated cascade (R-HSA-5654704)
  FRS-mediated FGFR3 signaling (R-HSA-5654706)
  PI-3K cascade (R-HSA-5654710)
  FRS-mediated FGFR4 signaling (R-HSA-5654712)
  SHC-mediated cascade (R-HSA-5654719)
  PI-3K cascade (R-HSA-5654720)
  Negative regulation of FGFR1 signaling (R-HSA-5654726)
  Negative regulation of FGFR2 signaling (R-HSA-5654727)
  Negative regulation of FGFR3 signaling (R-HSA-5654732)
  Negative regulation of FGFR4 signaling (R-HSA-5654733)
  Signaling by FGFR2 in disease (R-HSA-5655253)
  Signaling by FGFR1 in disease (R-HSA-5655302)
  Signaling by FGFR3 in disease (R-HSA-5655332)
  FGFRL1 modulation of FGFR1 signaling (R-HSA-5658623)
  RAF/MAP kinase cascade (R-HSA-5673001)
  PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling (R-HSA-6811558)
  Post-translational protein phosphorylation (R-HSA-8957275)
  PI3K Cascade (R-HSA-109704)

Molecular Interaction Atlas (MIA) of This DTT

1 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Burosumab	DMKUOQV	X-linked hypophosphataemia	5C63.22	Approved	[1]

References

• [1] 2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.