Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTPD1LL9)

• DOT Name: Protransforming growth factor alpha (TGFA)
• Gene Name: TGFA
• Related Disease: Tooth agenesis
• UniProt ID: TGFA_HUMAN
• PDB ID: 1GK5; 1MOX; 1YUF; 1YUG; 2TGF; 3E50; 3TGF; 4TGF; 5KN5; 7SZ5; 7SZ7
• Sequence:
  MVPSAGQLALFALGIVLAACQALENSTSPLSADPPVAAAVVSHFNDCPDSHTQFCFHGTC
  RFLVQEDKPACVCHSGYVGARCEHADLLAVVAASQKKQAITALVVVSIVALAVLIITCVL
  IHCCQVRKHCEWCRALICRHEKPSALLKGRTACCHSETVV
• Function: TGF alpha is a mitogenic polypeptide that is able to bind to the EGF receptor/EGFR and to act synergistically with TGF beta to promote anchorage-independent cell proliferation in soft agar.
• Tissue Specificity: Isoform 1, isoform 3 and isoform 4 are expressed in keratinocytes and tumor-derived cell lines.
• KEGG Pathway:
  EGFR tyrosine ki.se inhibitor resistance (hsa01521)
  MAPK sig.ling pathway (hsa04010)
  ErbB sig.ling pathway (hsa04012)
  Ras sig.ling pathway (hsa04014)
  Calcium sig.ling pathway (hsa04020)
  PI3K-Akt sig.ling pathway (hsa04151)
  Estrogen sig.ling pathway (hsa04915)
  Pathways in cancer (hsa05200)
  Colorectal cancer (hsa05210)
  Re.l cell carcinoma (hsa05211)
  Pancreatic cancer (hsa05212)
  Glioma (hsa05214)
  Prostate cancer (hsa05215)
  Non-small cell lung cancer (hsa05223)
  Hepatocellular carcinoma (hsa05225)
• Reactome Pathway:
  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)
  COPII-mediated vesicle transport (R-HSA-204005)
  EGFR interacts with phospholipase C-gamma (R-HSA-212718)
  Constitutive Signaling by Aberrant PI3K in Cancer (R-HSA-2219530)
  Inhibition of Signaling by Overexpressed EGFR (R-HSA-5638303)
  RAF/MAP kinase cascade (R-HSA-5673001)
  Cargo concentration in the ER (R-HSA-5694530)
  PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling (R-HSA-6811558)
  Cargo recognition for clathrin-mediated endocytosis (R-HSA-8856825)
  Clathrin-mediated endocytosis (R-HSA-8856828)
  TFAP2 (AP-2) family regulates transcription of growth factors and their receptors (R-HSA-8866910)
  Extra-nuclear estrogen signaling (R-HSA-9009391)
  Estrogen-dependent gene expression (R-HSA-9018519)
  Estrogen-dependent nuclear events downstream of ESR-membrane signaling (R-HSA-9634638)
  PIP3 activates AKT signaling (R-HSA-1257604)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Tooth agenesis	DIS1PWC7	Supportive	Autosomal dominant	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic trioxide	DM61TA4	Approved	Protransforming growth factor alpha (TGFA) decreases the response to substance of Arsenic trioxide.	[34]
Gefitinib	DM15F0X	Approved	Protransforming growth factor alpha (TGFA) decreases the response to substance of Gefitinib.	[35]
Crizotinib	DM4F29C	Approved	Protransforming growth factor alpha (TGFA) decreases the response to substance of Crizotinib.	[36]
NVP-TAE684	DMFZXI2	Investigative	Protransforming growth factor alpha (TGFA) decreases the response to substance of NVP-TAE684.	[36]

33 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 Protransforming growth factor alpha (TGFA).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Protransforming growth factor alpha (TGFA).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Protransforming growth factor alpha (TGFA).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Protransforming growth factor alpha (TGFA).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Protransforming growth factor alpha (TGFA).	[6]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Protransforming growth factor alpha (TGFA).	[7]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of Protransforming growth factor alpha (TGFA).	[8]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Protransforming growth factor alpha (TGFA).	[9]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Protransforming growth factor alpha (TGFA).	[10]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Protransforming growth factor alpha (TGFA).	[11]
Marinol	DM70IK5	Approved	Marinol increases the expression of Protransforming growth factor alpha (TGFA).	[12]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the expression of Protransforming growth factor alpha (TGFA).	[7]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of Protransforming growth factor alpha (TGFA).	[13]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of Protransforming growth factor alpha (TGFA).	[14]
Etoposide	DMNH3PG	Approved	Etoposide increases the expression of Protransforming growth factor alpha (TGFA).	[15]
Diclofenac	DMPIHLS	Approved	Diclofenac increases the expression of Protransforming growth factor alpha (TGFA).	[13]
Ethinyl estradiol	DMODJ40	Approved	Ethinyl estradiol increases the expression of Protransforming growth factor alpha (TGFA).	[17]
Lansoprazole	DMXYLQ3	Approved	Lansoprazole increases the expression of Protransforming growth factor alpha (TGFA).	[19]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Protransforming growth factor alpha (TGFA).	[20]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Protransforming growth factor alpha (TGFA).	[14]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Protransforming growth factor alpha (TGFA).	[21]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Protransforming growth factor alpha (TGFA).	[22]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Protransforming growth factor alpha (TGFA).	[23]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Protransforming growth factor alpha (TGFA).	[24]
Scriptaid	DM9JZ21	Preclinical	Scriptaid affects the expression of Protransforming growth factor alpha (TGFA).	[25]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Protransforming growth factor alpha (TGFA).	[14]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Protransforming growth factor alpha (TGFA).	[27]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Protransforming growth factor alpha (TGFA).	[28]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Protransforming growth factor alpha (TGFA).	[29]
D-glucose	DMMG2TO	Investigative	D-glucose increases the expression of Protransforming growth factor alpha (TGFA).	[30]
Cycloheximide	DMGDA3C	Investigative	Cycloheximide increases the expression of Protransforming growth factor alpha (TGFA).	[15]
Hydroxydimethylarsine Oxide	DMPS2B1	Investigative	Hydroxydimethylarsine Oxide increases the expression of Protransforming growth factor alpha (TGFA).	[31]
PHA-665752	DMCGX9U	Investigative	PHA-665752 increases the expression of Protransforming growth factor alpha (TGFA).	[33]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Irinotecan	DMP6SC2	Approved	Irinotecan increases the secretion of Protransforming growth factor alpha (TGFA).	[16]
Adenosine	DMM2NSK	Approved	Adenosine increases the secretion of Protransforming growth factor alpha (TGFA).	[18]
Batimastat	DM92VRP	Preclinical	Batimastat decreases the secretion of Protransforming growth factor alpha (TGFA).	[26]
carvacrol	DMINM2D	Investigative	carvacrol increases the secretion of Protransforming growth factor alpha (TGFA).	[32]

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