Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTANRJ0L)

• DOT Name: Pro-epidermal growth factor (EGF)
• Synonyms: EGF
• Gene Name: EGF
• Related Disease:
  Familial primary hypomagnesemia with normocalciuria and normocalcemia
  Renal hypomagnesemia 4
• UniProt ID: EGF_HUMAN
• PDB ID: 1IVO; 1JL9; 1NQL; 1P9J; 2KV4; 3NJP; 7OM4; 7SYD; 7SYE; 7SZ0; 7SZ1; 8HGO; 8HGS
• Pfam ID: PF00008 ; PF07645 ; PF14670 ; PF00058
• Sequence:
  MLLTLIILLPVVSKFSFVSLSAPQHWSCPEGTLAGNGNSTCVGPAPFLIFSHGNSIFRID
  TEGTNYEQLVVDAGVSVIMDFHYNEKRIYWVDLERQLLQRVFLNGSRQERVCNIEKNVSG
  MAINWINEEVIWSNQQEGIITVTDMKGNNSHILLSALKYPANVAVDPVERFIFWSSEVAG
  SLYRADLDGVGVKALLETSEKITAVSLDVLDKRLFWIQYNREGSNSLICSCDYDGGSVHI
  SKHPTQHNLFAMSLFGDRIFYSTWKMKTIWIANKHTGKDMVRINLHSSFVPLGELKVVHP
  LAQPKAEDDTWEPEQKLCKLRKGNCSSTVCGQDLQSHLCMCAEGYALSRDRKYCEDVNEC
  AFWNHGCTLGCKNTPGSYYCTCPVGFVLLPDGKRCHQLVSCPRNVSECSHDCVLTSEGPL
  CFCPEGSVLERDGKTCSGCSSPDNGGCSQLCVPLSPVSWECDCFPGYDLQLDEKSCAASG
  PQPFLLFANSQDIRHMHFDGTDYGTLLSQQMGMVYALDHDPVENKIYFAHTALKWIERAN
  MDGSQRERLIEEGVDVPEGLAVDWIGRRFYWTDRGKSLIGRSDLNGKRSKIITKENISQP
  RGIAVHPMAKRLFWTDTGINPRIESSSLQGLGRLVIASSDLIWPSGITIDFLTDKLYWCD
  AKQSVIEMANLDGSKRRRLTQNDVGHPFAVAVFEDYVWFSDWAMPSVMRVNKRTGKDRVR
  LQGSMLKPSSLVVVHPLAKPGADPCLYQNGGCEHICKKRLGTAWCSCREGFMKASDGKTC
  LALDGHQLLAGGEVDLKNQVTPLDILSKTRVSEDNITESQHMLVAEIMVSDQDDCAPVGC
  SMYARCISEGEDATCQCLKGFAGDGKLCSDIDECEMGVPVCPPASSKCINTEGGYVCRCS
  EGYQGDGIHCLDIDECQLGEHSCGENASCTNTEGGYTCMCAGRLSEPGLICPDSTPPPHL
  REDDHHYSVRNSDSECPLSHDGYCLHDGVCMYIEALDKYACNCVVGYIGERCQYRDLKWW
  ELRHAGHGQQQKVIVVAVCVVVLVMLLLLSLWGAHYYRTQKLLSKNPKNPYEESSRDVRS
  RRPADTEDGMSSCPQPWFVVIKEHQDLKNGGQPVAGEDGQAADGSMQPTSWRQEPQLCGM
  GTEQGCWIPVSSDKGSCPQVMERSFHMPSYGTQTLEGGVEKPHSLLSANPLWQQRALDPP
  HQMELTQ
• Function: EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. Magnesiotropic hormone that stimulates magnesium reabsorption in the renal distal convoluted tubule via engagement of EGFR and activation of the magnesium channel TRPM6. Can induce neurite outgrowth in motoneurons of the pond snail Lymnaea stagnalis in vitro.
• Tissue Specificity: Expressed in kidney, salivary gland, cerebrum and prostate.
• KEGG Pathway:
  EGFR tyrosine ki.se inhibitor resistance (hsa01521)
  MAPK sig.ling pathway (hsa04010)
  ErbB sig.ling pathway (hsa04012)
  Ras sig.ling pathway (hsa04014)
  Rap1 sig.ling pathway (hsa04015)
  Calcium sig.ling pathway (hsa04020)
  HIF-1 sig.ling pathway (hsa04066)
  FoxO sig.ling pathway (hsa04068)
  Phospholipase D sig.ling pathway (hsa04072)
  PI3K-Akt sig.ling pathway (hsa04151)
  Focal adhesion (hsa04510)
  Gap junction (hsa04540)
  JAK-STAT sig.ling pathway (hsa04630)
  Regulation of actin cytoskeleton (hsa04810)
  Hepatitis C (hsa05160)
  Human papillomavirus infection (hsa05165)
  Pathways in cancer (hsa05200)
  Chemical carcinogenesis - receptor activation (hsa05207)
  Chemical carcinogenesis - reactive oxygen species (hsa05208)
  Colorectal cancer (hsa05210)
  Pancreatic cancer (hsa05212)
  Endometrial cancer (hsa05213)
  Glioma (hsa05214)
  Prostate cancer (hsa05215)
  Melanoma (hsa05218)
  Bladder cancer (hsa05219)
  Non-small cell lung cancer (hsa05223)
  Breast cancer (hsa05224)
  Gastric cancer (hsa05226)
  Choline metabolism in cancer (hsa05231)
  PD-L1 expression and PD-1 checkpoint pathway in cancer (hsa05235)
• Reactome Pathway:
  Signaling by ERBB2 (R-HSA-1227986)
  Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants (R-HSA-1236382)
  Signaling by ERBB4 (R-HSA-1236394)
  SHC1 events in ERBB2 signaling (R-HSA-1250196)
  PLCG1 events in ERBB2 signaling (R-HSA-1251932)
  PIP3 activates AKT signaling (R-HSA-1257604)
  Signaling by EGFR (R-HSA-177929)
  GRB2 events in EGFR signaling (R-HSA-179812)
  GAB1 signalosome (R-HSA-180292)
  SHC1 events in EGFR signaling (R-HSA-180336)
  EGFR downregulation (R-HSA-182971)
  GRB2 events in ERBB2 signaling (R-HSA-1963640)
  PI3K events in ERBB2 signaling (R-HSA-1963642)
  EGFR interacts with phospholipase C-gamma (R-HSA-212718)
  Constitutive Signaling by Aberrant PI3K in Cancer (R-HSA-2219530)
  Constitutive Signaling by EGFRvIII (R-HSA-5637810)
  Inhibition of Signaling by Overexpressed EGFR (R-HSA-5638303)
  RAF/MAP kinase cascade (R-HSA-5673001)
  ERBB2 Regulates Cell Motility (R-HSA-6785631)
  PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling (R-HSA-6811558)
  ERBB2 Activates PTK6 Signaling (R-HSA-8847993)
  Cargo recognition for clathrin-mediated endocytosis (R-HSA-8856825)
  Clathrin-mediated endocytosis (R-HSA-8856828)
  Downregulation of ERBB2 signaling (R-HSA-8863795)
  Extra-nuclear estrogen signaling (R-HSA-9009391)
  NOTCH3 Activation and Transmission of Signal to the Nucleus (R-HSA-9013507)
  Estrogen-dependent nuclear events downstream of ESR-membrane signaling (R-HSA-9634638)
  Signaling by ERBB2 KD Mutants (R-HSA-9664565)
  Signaling by ERBB2 ECD mutants (R-HSA-9665348)
  Signaling by ERBB2 TMD/JMD mutants (R-HSA-9665686)
  NFE2L2 regulating tumorigenic genes (R-HSA-9818030)
  Platelet degranulation (R-HSA-114608)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Familial primary hypomagnesemia with normocalciuria and normocalcemia	DISZNFLZ	Supportive	Autosomal dominant	[1]
Renal hypomagnesemia 4	DISQGH7M	Limited	Autosomal dominant	[2]

This DOT Affected the Regulation of Drug Effects of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Dinoprostone	DMTYOPD	Approved	Pro-epidermal growth factor (EGF) increases the abundance of Dinoprostone.	[43]

This DOT Affected the Drug Response of 3 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Crizotinib	DM4F29C	Approved	Pro-epidermal growth factor (EGF) decreases the response to substance of Crizotinib.	[44]
Acetaldehyde	DMJFKG4	Investigative	Pro-epidermal growth factor (EGF) decreases the response to substance of Acetaldehyde.	[45]
NVP-TAE684	DMFZXI2	Investigative	Pro-epidermal growth factor (EGF) decreases the response to substance of NVP-TAE684.	[44]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Pro-epidermal growth factor (EGF).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Pro-epidermal growth factor (EGF).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Pro-epidermal growth factor (EGF).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Pro-epidermal growth factor (EGF).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Pro-epidermal growth factor (EGF).	[7]
Estradiol	DMUNTE3	Approved	Estradiol affects the activity of Pro-epidermal growth factor (EGF).	[8]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of Pro-epidermal growth factor (EGF).	[9]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Pro-epidermal growth factor (EGF).	[10]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Pro-epidermal growth factor (EGF).	[11]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Pro-epidermal growth factor (EGF).	[12]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Pro-epidermal growth factor (EGF).	[13]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Pro-epidermal growth factor (EGF).	[14]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Pro-epidermal growth factor (EGF).	[15]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of Pro-epidermal growth factor (EGF).	[16]
Fulvestrant	DM0YZC6	Approved	Fulvestrant affects the activity of Pro-epidermal growth factor (EGF).	[8]
Niclosamide	DMJAGXQ	Approved	Niclosamide decreases the expression of Pro-epidermal growth factor (EGF).	[17]
Paclitaxel	DMLB81S	Approved	Paclitaxel decreases the expression of Pro-epidermal growth factor (EGF).	[18]
Gemcitabine	DMSE3I7	Approved	Gemcitabine decreases the expression of Pro-epidermal growth factor (EGF).	[19]
Ardeparin	DMYRX8B	Approved	Ardeparin decreases the activity of Pro-epidermal growth factor (EGF).	[20]
Adenosine	DMM2NSK	Approved	Adenosine increases the expression of Pro-epidermal growth factor (EGF).	[21]
Gentamicin	DMKINJO	Approved	Gentamicin decreases the expression of Pro-epidermal growth factor (EGF).	[22]
Nevirapine	DM6HX9B	Approved	Nevirapine decreases the expression of Pro-epidermal growth factor (EGF).	[23]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Pro-epidermal growth factor (EGF).	[16]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the activity of Pro-epidermal growth factor (EGF).	[24]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate decreases the expression of Pro-epidermal growth factor (EGF).	[25]
Curcumin	DMQPH29	Phase 3	Curcumin decreases the activity of Pro-epidermal growth factor (EGF).	[26]
Napabucasin	DMDZ6Q3	Phase 3	Napabucasin decreases the expression of Pro-epidermal growth factor (EGF).	[27]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Pro-epidermal growth factor (EGF).	[28]
DNCB	DMDTVYC	Phase 2	DNCB decreases the expression of Pro-epidermal growth factor (EGF).	[29]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate increases the expression of Pro-epidermal growth factor (EGF).	[30]
Puerarin	DMJIMXH	Phase 2	Puerarin decreases the expression of Pro-epidermal growth factor (EGF).	[28]
ACYLINE	DM9GRTK	Phase 2	ACYLINE decreases the expression of Pro-epidermal growth factor (EGF).	[31]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Pro-epidermal growth factor (EGF).	[33]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Pro-epidermal growth factor (EGF).	[34]
Steroid derivative 1	DMB0NVQ	Patented	Steroid derivative 1 decreases the expression of Pro-epidermal growth factor (EGF).	[17]
MG-132	DMKA2YS	Preclinical	MG-132 increases the expression of Pro-epidermal growth factor (EGF).	[35]
Taxifolin	DMQJSF9	Preclinical	Taxifolin decreases the expression of Pro-epidermal growth factor (EGF).	[36]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Pro-epidermal growth factor (EGF).	[37]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Pro-epidermal growth factor (EGF).	[38]
2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE	DMNQL17	Investigative	2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE decreases the expression of Pro-epidermal growth factor (EGF).	[39]
Cordycepin	DM72Y01	Investigative	Cordycepin increases the expression of Pro-epidermal growth factor (EGF).	[21]
Lead acetate	DML0GZ2	Investigative	Lead acetate increases the expression of Pro-epidermal growth factor (EGF).	[40]
Chlorogenic acid	DM2Y3P4	Investigative	Chlorogenic acid decreases the expression of Pro-epidermal growth factor (EGF).	[28]
RHEIN	DMS6IJ0	Investigative	RHEIN decreases the expression of Pro-epidermal growth factor (EGF).	[41]

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 increases the methylation of Pro-epidermal growth factor (EGF).	[32]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Leupeptin	DMU075F	Investigative	Leupeptin decreases the degradation of Pro-epidermal growth factor (EGF).	[42]

References

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