Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTGHUA23)

• DOT Name: Hepatocyte growth factor (HGF)
• Synonyms: Hepatopoietin-A; Scatter factor; SF
• Gene Name: HGF
• Related Disease:
  Autosomal recessive nonsyndromic hearing loss 39
  Nonsyndromic genetic hearing loss
  Hearing loss, autosomal recessive
• UniProt ID: HGF_HUMAN
• PDB ID: 1BHT ; 1GMN ; 1GMO ; 1GP9 ; 1NK1 ; 1SHY ; 1SI5 ; 2HGF ; 2QJ2 ; 3HMS ; 3HMT ; 3HN4 ; 3MKP ; 3SP8 ; 4D3C ; 4K3J ; 4O3T ; 4O3U ; 5COE ; 5CP9 ; 5CS1 ; 5CS3 ; 5CS5 ; 5CS9 ; 5CSQ ; 5CT1 ; 5CT2 ; 5CT3 ; 7MO7 ; 7MO8 ; 7MO9 ; 7MOA ; 7MOB ; 7OCL ; 7OCM
• Pfam ID: PF00051 ; PF00024 ; PF00089
• Sequence:
  MWVTKLLPALLLQHVLLHLLLLPIAIPYAEGQRKRRNTIHEFKKSAKTTLIKIDPALKIK
  TKKVNTADQCANRCTRNKGLPFTCKAFVFDKARKQCLWFPFNSMSSGVKKEFGHEFDLYE
  NKDYIRNCIIGKGRSYKGTVSITKSGIKCQPWSSMIPHEHSFLPSSYRGKDLQENYCRNP
  RGEEGGPWCFTSNPEVRYEVCDIPQCSEVECMTCNGESYRGLMDHTESGKICQRWDHQTP
  HRHKFLPERYPDKGFDDNYCRNPDGQPRPWCYTLDPHTRWEYCAIKTCADNTMNDTDVPL
  ETTECIQGQGEGYRGTVNTIWNGIPCQRWDSQYPHEHDMTPENFKCKDLRENYCRNPDGS
  ESPWCFTTDPNIRVGYCSQIPNCDMSHGQDCYRGNGKNYMGNLSQTRSGLTCSMWDKNME
  DLHRHIFWEPDASKLNENYCRNPDDDAHGPWCYTGNPLIPWDYCPISRCEGDTTPTIVNL
  DHPVISCAKTKQLRVVNGIPTRTNIGWMVSLRYRNKHICGGSLIKESWVLTARQCFPSRD
  LKDYEAWLGIHDVHGRGDEKCKQVLNVSQLVYGPEGSDLVLMKLARPAVLDDFVSTIDLP
  NYGCTIPEKTSCSVYGWGYTGLINYDGLLRVAHLYIMGNEKCSQHHRGKVTLNESEICAG
  AEKIGSGPCEGDYGGPLVCEQHKMRMVLGVIVPGRGCAIPNRPGIFVRVAYYAKWIHKII
  LTYKVPQS
• Function: Potent mitogen for mature parenchymal hepatocyte cells, seems to be a hepatotrophic factor, and acts as a growth factor for a broad spectrum of tissues and cell types. Activating ligand for the receptor tyrosine kinase MET by binding to it and promoting its dimerization. Activates MAPK signaling following TMPRSS13 cleavage and activation.
• KEGG Pathway:
  EGFR tyrosine ki.se inhibitor resistance (hsa01521)
  MAPK sig.ling pathway (hsa04010)
  Ras sig.ling pathway (hsa04014)
  Rap1 sig.ling pathway (hsa04015)
  Calcium sig.ling pathway (hsa04020)
  PI3K-Akt sig.ling pathway (hsa04151)
  Focal adhesion (hsa04510)
  Malaria (hsa05144)
  Pathways in cancer (hsa05200)
  Proteoglycans in cancer (hsa05205)
  Chemical carcinogenesis - reactive oxygen species (hsa05208)
  Re.l cell carcinoma (hsa05211)
  Melanoma (hsa05218)
  Non-small cell lung cancer (hsa05223)
  Hepatocellular carcinoma (hsa05225)
  Gastric cancer (hsa05226)
• Reactome Pathway:
  PIP3 activates AKT signaling (R-HSA-1257604)
  Interleukin-7 signaling (R-HSA-1266695)
  Constitutive Signaling by Aberrant PI3K in Cancer (R-HSA-2219530)
  RAF/MAP kinase cascade (R-HSA-5673001)
  Interleukin-4 and Interleukin-13 signaling (R-HSA-6785807)
  MET Receptor Activation (R-HSA-6806942)
  Negative regulation of MET activity (R-HSA-6807004)
  PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling (R-HSA-6811558)
  MET activates RAS signaling (R-HSA-8851805)
  MET activates PI3K/AKT signaling (R-HSA-8851907)
  MET activates PTPN11 (R-HSA-8865999)
  MET activates PTK2 signaling (R-HSA-8874081)
  MET interacts with TNS proteins (R-HSA-8875513)
  MET activates RAP1 and RAC1 (R-HSA-8875555)
  MET receptor recycling (R-HSA-8875656)
  MET activates STAT3 (R-HSA-8875791)
  Drug-mediated inhibition of MET activation (R-HSA-9734091)
  Platelet degranulation (R-HSA-114608)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autosomal recessive nonsyndromic hearing loss 39	DISQHS15	Strong	Autosomal recessive	[1]
Nonsyndromic genetic hearing loss	DISZX61P	Moderate	Autosomal recessive	[2]
Hearing loss, autosomal recessive	DIS8G9R9	Supportive	Autosomal recessive	[3]

This DOT Affected the Drug Response of 4 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Cytarabine	DMZD5QR	Approved	Hepatocyte growth factor (HGF) increases the Cell-mediated cytotoxicity ADR of Cytarabine.	[37]
Sorafenib	DMS8IFC	Approved	Hepatocyte growth factor (HGF) decreases the response to substance of Sorafenib.	[38]
Ribavirin	DMEYLH9	Phase 1 Trial	Hepatocyte growth factor (HGF) increases the Hepatic function abnormal ADR of Ribavirin.	[37]
NVP-TAE684	DMFZXI2	Investigative	Hepatocyte growth factor (HGF) decreases the response to substance of NVP-TAE684.	[39]

39 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Hepatocyte growth factor (HGF).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Hepatocyte growth factor (HGF).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Hepatocyte growth factor (HGF).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Hepatocyte growth factor (HGF).	[7]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of Hepatocyte growth factor (HGF).	[8]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Hepatocyte growth factor (HGF).	[9]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Hepatocyte growth factor (HGF).	[10]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Hepatocyte growth factor (HGF).	[11]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Hepatocyte growth factor (HGF).	[12]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Hepatocyte growth factor (HGF).	[13]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Hepatocyte growth factor (HGF).	[6]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone increases the expression of Hepatocyte growth factor (HGF).	[14]
Azacitidine	DMTA5OE	Approved	Azacitidine increases the expression of Hepatocyte growth factor (HGF).	[15]
Melphalan	DMOLNHF	Approved	Melphalan decreases the expression of Hepatocyte growth factor (HGF).	[16]
Alitretinoin	DMME8LH	Approved	Alitretinoin decreases the expression of Hepatocyte growth factor (HGF).	[6]
Thalidomide	DM70BU5	Approved	Thalidomide decreases the activity of Hepatocyte growth factor (HGF).	[17]
Hydrocortisone	DMGEMB7	Approved	Hydrocortisone decreases the expression of Hepatocyte growth factor (HGF).	[13]
Rofecoxib	DM3P5DA	Approved	Rofecoxib decreases the expression of Hepatocyte growth factor (HGF).	[18]
Ardeparin	DMYRX8B	Approved	Ardeparin increases the expression of Hepatocyte growth factor (HGF).	[19]
Sevoflurane	DMC9O43	Approved	Sevoflurane increases the expression of Hepatocyte growth factor (HGF).	[20]
Nifedipine	DMSVOZT	Approved	Nifedipine increases the expression of Hepatocyte growth factor (HGF).	[22]
Etodolac	DM6WJO9	Approved	Etodolac decreases the expression of Hepatocyte growth factor (HGF).	[23]
Berberine	DMC5Q8X	Phase 4	Berberine increases the expression of Hepatocyte growth factor (HGF).	[14]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Hepatocyte growth factor (HGF).	[24]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Hepatocyte growth factor (HGF).	[25]
Curcumin	DMQPH29	Phase 3	Curcumin decreases the expression of Hepatocyte growth factor (HGF).	[26]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Hepatocyte growth factor (HGF).	[27]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate increases the expression of Hepatocyte growth factor (HGF).	[28]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Hepatocyte growth factor (HGF).	[30]
Sphingosine-1-Phosphate	DMJCQKA	Phase 1	Sphingosine-1-Phosphate increases the expression of Hepatocyte growth factor (HGF).	[31]
NS398	DMINUWH	Terminated	NS398 decreases the expression of Hepatocyte growth factor (HGF).	[23]
Calphostin C	DM9X2D0	Terminated	Calphostin C decreases the expression of Hepatocyte growth factor (HGF).	[32]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Hepatocyte growth factor (HGF).	[33]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Hepatocyte growth factor (HGF).	[34]
Glyphosate	DM0AFY7	Investigative	Glyphosate decreases the expression of Hepatocyte growth factor (HGF).	[35]
4-hydroxy-2-nonenal	DM2LJFZ	Investigative	4-hydroxy-2-nonenal decreases the expression of Hepatocyte growth factor (HGF).	[11]
QUERCITRIN	DM1DH96	Investigative	QUERCITRIN increases the expression of Hepatocyte growth factor (HGF).	[36]
15-deoxy-Delta(12, 14)-prostaglandin J(2)	DM8VUX3	Investigative	15-deoxy-Delta(12, 14)-prostaglandin J(2) increases the expression of Hepatocyte growth factor (HGF).	[14]
TTNPB	DMSABD0	Investigative	TTNPB decreases the expression of Hepatocyte growth factor (HGF).	[6]

2 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Nevirapine	DM6HX9B	Approved	Nevirapine decreases the secretion of Hepatocyte growth factor (HGF).	[21]
Efavirenz	DMC0GSJ	Approved	Efavirenz increases the secretion of Hepatocyte growth factor (HGF).	[21]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Hepatocyte growth factor (HGF).	[29]

References

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