Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTFP7AA8)

• DOT Name: ATP-dependent 6-phosphofructokinase, platelet type (PFKP)
• Synonyms: ATP-PFK; PFK-P; EC 2.7.1.11; 6-phosphofructokinase type C; Phosphofructo-1-kinase isozyme C; PFK-C; Phosphohexokinase
• Gene Name: PFKP
• Related Disease:
  Adenocarcinoma
  Breast cancer
  Breast carcinoma
  Intrahepatic cholangiocarcinoma
  Neoplasm
  Renal tubular acidosis
  Her2-receptor negative breast cancer
  HER2/NEU overexpressing breast cancer
  Pancreatic cancer
  Advanced cancer
• UniProt ID: PFKAP_HUMAN
• PDB ID: 4RH3; 4U1R; 4WL0; 4XYJ; 4XYK; 4XZ2; 7TFF
• EC Number: 2.7.1.11
• Pfam ID: PF00365
• Sequence:
  MDADDSRAPKGSLRKFLEHLSGAGKAIGVLTSGGDAQGMNAAVRAVVRMGIYVGAKVYFI
  YEGYQGMVDGGSNIAEADWESVSSILQVGGTIIGSARCQAFRTREGRLKAACNLLQRGIT
  NLCVIGGDGSLTGANLFRKEWSGLLEELARNGQIDKEAVQKYAYLNVVGMVGSIDNDFCG
  TDMTIGTDSALHRIIEVVDAIMTTAQSHQRTFVLEVMGRHCGYLALVSALACGADWVFLP
  ESPPEEGWEEQMCVKLSENRARKKRLNIIIVAEGAIDTQNKPITSEKIKELVVTQLGYDT
  RVTILGHVQRGGTPSAFDRILASRMGVEAVIALLEATPDTPACVVSLNGNHAVRLPLMEC
  VQMTQDVQKAMDERRFQDAVRLRGRSFAGNLNTYKRLAIKLPDDQIPKTNCNVAVINVGA
  PAAGMNAAVRSAVRVGIADGHRMLAIYDGFDGFAKGQIKEIGWTDVGGWTGQGGSILGTK
  RVLPGKYLEEIATQMRTHSINALLIIGGFEAYLGLLELSAAREKHEEFCVPMVMVPATVS
  NNVPGSDFSIGADTALNTITDTCDRIKQSASGTKRRVFIIETMGGYCGYLANMGGLAAGA
  DAAYIFEEPFDIRDLQSNVEHLTEKMKTTIQRGLVLRNESCSENYTTDFIYQLYSEEGKG
  VFDCRKNVLGHMQQGGAPSPFDRNFGTKISARAMEWITAKLKEARGRGKKFTTDDSICVL
  GISKRNVIFQPVAELKKQTDFEHRIPKEQWWLKLRPLMKILAKYKASYDVSDSGQLEHVQ
  PWSV
• Function: Catalyzes the phosphorylation of D-fructose 6-phosphate to fructose 1,6-bisphosphate by ATP, the first committing step of glycolysis.
• KEGG Pathway:
  Glycolysis / Gluconeogenesis (hsa00010)
  Pentose phosphate pathway (hsa00030)
  Fructose and mannose metabolism (hsa00051)
  Galactose metabolism (hsa00052)
  Metabolic pathways (hsa01100)
  Carbon metabolism (hsa01200)
  Biosynthesis of amino acids (hsa01230)
  R. degradation (hsa03018)
  HIF-1 sig.ling pathway (hsa04066)
  AMPK sig.ling pathway (hsa04152)
  Thyroid hormone sig.ling pathway (hsa04919)
  Glucagon sig.ling pathway (hsa04922)
  Central carbon metabolism in cancer (hsa05230)
• Reactome Pathway: Glycolysis (R-HSA-70171)
• BioCyc Pathway: MetaCyc:HS00894-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adenocarcinoma	DIS3IHTY	Strong	Biomarker	[1]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[2]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[2]
Intrahepatic cholangiocarcinoma	DIS6GOC8	Strong	Altered Expression	[3]
Neoplasm	DISZKGEW	Strong	Altered Expression	[4]
Renal tubular acidosis	DISE1NDR	Strong	Genetic Variation	[5]
Her2-receptor negative breast cancer	DISS605N	moderate	Biomarker	[6]
HER2/NEU overexpressing breast cancer	DISYKID5	moderate	Biomarker	[6]
Pancreatic cancer	DISJC981	moderate	Biomarker	[7]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[8]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	ATP-dependent 6-phosphofructokinase, platelet type (PFKP) affects the response to substance of Cisplatin.	[33]
Josamycin	DMKJ8LB	Approved	ATP-dependent 6-phosphofructokinase, platelet type (PFKP) decreases the response to substance of Josamycin.	[34]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of ATP-dependent 6-phosphofructokinase, platelet type (PFKP).	[9]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of ATP-dependent 6-phosphofructokinase, platelet type (PFKP).	[18]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of ATP-dependent 6-phosphofructokinase, platelet type (PFKP).	[24]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of ATP-dependent 6-phosphofructokinase, platelet type (PFKP).	[10]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of ATP-dependent 6-phosphofructokinase, platelet type (PFKP).	[11]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of ATP-dependent 6-phosphofructokinase, platelet type (PFKP).	[12]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of ATP-dependent 6-phosphofructokinase, platelet type (PFKP).	[13]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of ATP-dependent 6-phosphofructokinase, platelet type (PFKP).	[14]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of ATP-dependent 6-phosphofructokinase, platelet type (PFKP).	[15]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of ATP-dependent 6-phosphofructokinase, platelet type (PFKP).	[16]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of ATP-dependent 6-phosphofructokinase, platelet type (PFKP).	[17]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of ATP-dependent 6-phosphofructokinase, platelet type (PFKP).	[17]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of ATP-dependent 6-phosphofructokinase, platelet type (PFKP).	[19]
Liothyronine	DM6IR3P	Approved	Liothyronine increases the expression of ATP-dependent 6-phosphofructokinase, platelet type (PFKP).	[20]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of ATP-dependent 6-phosphofructokinase, platelet type (PFKP).	[17]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of ATP-dependent 6-phosphofructokinase, platelet type (PFKP).	[21]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of ATP-dependent 6-phosphofructokinase, platelet type (PFKP).	[10]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of ATP-dependent 6-phosphofructokinase, platelet type (PFKP).	[22]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of ATP-dependent 6-phosphofructokinase, platelet type (PFKP).	[23]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of ATP-dependent 6-phosphofructokinase, platelet type (PFKP).	[25]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of ATP-dependent 6-phosphofructokinase, platelet type (PFKP).	[26]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of ATP-dependent 6-phosphofructokinase, platelet type (PFKP).	[27]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of ATP-dependent 6-phosphofructokinase, platelet type (PFKP).	[28]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of ATP-dependent 6-phosphofructokinase, platelet type (PFKP).	[29]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of ATP-dependent 6-phosphofructokinase, platelet type (PFKP).	[30]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of ATP-dependent 6-phosphofructokinase, platelet type (PFKP).	[31]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of ATP-dependent 6-phosphofructokinase, platelet type (PFKP).	[32]

References

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