Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZU4G9W)

• DOT Name: Alkaline phosphatase, placental type (ALPP)
• Synonyms: EC 3.1.3.1; Alkaline phosphatase Regan isozyme; Placental alkaline phosphatase 1; PLAP-1
• Gene Name: ALPP
• Related Disease:
  Choriocarcinoma
  Pancreatic cancer
  Type-1/2 diabetes
  Acute myelogenous leukaemia
  Advanced cancer
  Ankylosing spondylitis
  Bladder cancer
  Bone osteosarcoma
  Carcinoma
  Cervical cancer
  Cervical carcinoma
  Clear cell renal carcinoma
  Colon cancer
  Colon carcinoma
  Congenital disorder of glycosylation
  Epithelial ovarian cancer
  Gastric cancer
  Glioblastoma multiforme
  Hepatocellular carcinoma
  Hypercalcaemia
  Liver cirrhosis
  Lung cancer
  Lung carcinoma
  Nasopharyngeal carcinoma
  Non-alcoholic fatty liver disease
  Osteosarcoma
  Ovarian cancer
  Prostate cancer
  Prostate carcinoma
  Pyropoikilocytosis, hereditary
  Renal cell carcinoma
  Stomach cancer
  Urinary bladder cancer
  Urinary bladder neoplasm
  Alzheimer disease
  Amyotrophic lateral sclerosis
  Hepatitis C virus infection
  Huntington disease
  Leukemia
  Rheumatoid arthritis
  Breast cancer
  Breast carcinoma
  Familial hypocalciuric hypercalcemia 1
  Hypophosphatasia
  Melanoma
  Metastatic malignant neoplasm
  Neuroblastoma
  Osteoporosis
  Plasma cell myeloma
• UniProt ID: PPB1_HUMAN
• PDB ID: 1EW2; 1ZEB; 1ZED; 1ZEF; 2GLQ; 3MK0; 3MK1; 3MK2
• EC Number: 3.1.3.1
• Pfam ID: PF00245
• Sequence:
  MLGPCMLLLLLLLGLRLQLSLGIIPVEEENPDFWNREAAEALGAAKKLQPAQTAAKNLII
  FLGDGMGVSTVTAARILKGQKKDKLGPEIPLAMDRFPYVALSKTYNVDKHVPDSGATATA
  YLCGVKGNFQTIGLSAAARFNQCNTTRGNEVISVMNRAKKAGKSVGVVTTTRVQHASPAG
  TYAHTVNRNWYSDADVPASARQEGCQDIATQLISNMDIDVILGGGRKYMFRMGTPDPEYP
  DDYSQGGTRLDGKNLVQEWLAKRQGARYVWNRTELMQASLDPSVTHLMGLFEPGDMKYEI
  HRDSTLDPSLMEMTEAALRLLSRNPRGFFLFVEGGRIDHGHHESRAYRALTETIMFDDAI
  ERAGQLTSEEDTLSLVTADHSHVFSFGGYPLRGSSIFGLAPGKARDRKAYTVLLYGNGPG
  YVLKDGARPDVTESESGSPEYRQQSAVPLDEETHAGEDVAVFARGPQAHLVHGVQEQTFI
  AHVMAFAACLEPYTACDLAPPAGTTDAAHPGRSVVPALLPLLAGTLLLLETATAP
• Function: Alkaline phosphatase that can hydrolyze various phosphate compounds.
• Tissue Specificity: Detected in placenta (at protein level).
• KEGG Pathway:
  Thiamine metabolism (hsa00730)
  Folate biosynthesis (hsa00790)
  Metabolic pathways (hsa01100)
  Biosynthesis of cofactors (hsa01240)
• Reactome Pathway: Intra-Golgi traffic (R-HSA-6811438)

Molecular Interaction Atlas (MIA) of This DOT

49 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Choriocarcinoma	DISDBVNL	Definitive	Altered Expression	[1]
Pancreatic cancer	DISJC981	Definitive	Biomarker	[2]
Type-1/2 diabetes	DISIUHAP	Definitive	Biomarker	[3]
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[4]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[5]
Ankylosing spondylitis	DISRC6IR	Strong	Altered Expression	[6]
Bladder cancer	DISUHNM0	Strong	Genetic Variation	[7]
Bone osteosarcoma	DIST1004	Strong	Biomarker	[8]
Carcinoma	DISH9F1N	Strong	Altered Expression	[9]
Cervical cancer	DISFSHPF	Strong	Altered Expression	[10]
Cervical carcinoma	DIST4S00	Strong	Altered Expression	[10]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[11]
Colon cancer	DISVC52G	Strong	Altered Expression	[12]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[12]
Congenital disorder of glycosylation	DIS400QP	Strong	Genetic Variation	[13]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[14]
Gastric cancer	DISXGOUK	Strong	Biomarker	[15]
Glioblastoma multiforme	DISK8246	Strong	Genetic Variation	[16]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[17]
Hypercalcaemia	DISKQ2K7	Strong	Biomarker	[18]
Liver cirrhosis	DIS4G1GX	Strong	Biomarker	[19]
Lung cancer	DISCM4YA	Strong	Biomarker	[20]
Lung carcinoma	DISTR26C	Strong	Biomarker	[20]
Nasopharyngeal carcinoma	DISAOTQ0	Strong	Biomarker	[21]
Non-alcoholic fatty liver disease	DISDG1NL	Strong	Biomarker	[22]
Osteosarcoma	DISLQ7E2	Strong	Biomarker	[8]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[14]
Prostate cancer	DISF190Y	Strong	Biomarker	[23]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[23]
Pyropoikilocytosis, hereditary	DISZGN3B	Strong	Biomarker	[24]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[11]
Stomach cancer	DISKIJSX	Strong	Biomarker	[15]
Urinary bladder cancer	DISDV4T7	Strong	Genetic Variation	[7]
Urinary bladder neoplasm	DIS7HACE	Strong	Genetic Variation	[7]
Alzheimer disease	DISF8S70	moderate	Biomarker	[25]
Amyotrophic lateral sclerosis	DISF7HVM	moderate	Biomarker	[25]
Hepatitis C virus infection	DISQ0M8R	moderate	Genetic Variation	[26]
Huntington disease	DISQPLA4	moderate	Biomarker	[25]
Leukemia	DISNAKFL	moderate	Biomarker	[27]
Rheumatoid arthritis	DISTSB4J	moderate	Altered Expression	[28]
Breast cancer	DIS7DPX1	Limited	Biomarker	[29]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[29]
Familial hypocalciuric hypercalcemia 1	DISPW6O5	Limited	Genetic Variation	[30]
Hypophosphatasia	DISCQ0O2	Limited	Biomarker	[31]
Melanoma	DIS1RRCY	Limited	Biomarker	[32]
Metastatic malignant neoplasm	DIS86UK6	Limited	Biomarker	[33]
Neuroblastoma	DISVZBI4	Limited	Biomarker	[34]
Osteoporosis	DISF2JE0	Limited	Altered Expression	[35]
Plasma cell myeloma	DIS0DFZ0	Limited	Biomarker	[36]

This DOT Affected the Biotransformations of 3 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Testosterone	DM7HUNW	Approved	Alkaline phosphatase, placental type (ALPP) increases the chemical synthesis of Testosterone.	[55]
Estrone	DM5T6US	Approved	Alkaline phosphatase, placental type (ALPP) increases the chemical synthesis of Estrone.	[55]
4-nitrophenyl phosphate	DMBX4UJ	Investigative	Alkaline phosphatase, placental type (ALPP) increases the chemical synthesis of 4-nitrophenyl phosphate.	[55]

This DOT Affected the Drug Response of 5 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Methotrexate	DM2TEOL	Approved	Alkaline phosphatase, placental type (ALPP) affects the response to substance of Methotrexate.	[56]
Dexamethasone	DMMWZET	Approved	Alkaline phosphatase, placental type (ALPP) increases the Bone disorder ADR of Dexamethasone.	[57]
Etoposide	DMNH3PG	Approved	Alkaline phosphatase, placental type (ALPP) affects the response to substance of Etoposide.	[56]
Lidocaine	DML4ZOT	Approved	Alkaline phosphatase, placental type (ALPP) increases the Pyrexia ADR of Lidocaine.	[57]
Paricalcitol	DMYBV3G	Approved	Alkaline phosphatase, placental type (ALPP) increases the Iron and trace metal metabolism disorders ADR of Paricalcitol.	[57]

4 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 Alkaline phosphatase, placental type (ALPP).	[37]
Decitabine	DMQL8XJ	Approved	Decitabine affects the methylation of Alkaline phosphatase, placental type (ALPP).	[42]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Alkaline phosphatase, placental type (ALPP).	[48]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Alkaline phosphatase, placental type (ALPP).	[51]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Alkaline phosphatase, placental type (ALPP).	[38]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Alkaline phosphatase, placental type (ALPP).	[39]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Alkaline phosphatase, placental type (ALPP).	[40]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Alkaline phosphatase, placental type (ALPP).	[41]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Alkaline phosphatase, placental type (ALPP).	[43]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Alkaline phosphatase, placental type (ALPP).	[44]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Alkaline phosphatase, placental type (ALPP).	[45]
Ethinyl estradiol	DMODJ40	Approved	Ethinyl estradiol increases the expression of Alkaline phosphatase, placental type (ALPP).	[46]
Isoproterenol	DMK7MEY	Approved	Isoproterenol increases the expression of Alkaline phosphatase, placental type (ALPP).	[47]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Alkaline phosphatase, placental type (ALPP).	[39]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Alkaline phosphatase, placental type (ALPP).	[49]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Alkaline phosphatase, placental type (ALPP).	[39]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Alkaline phosphatase, placental type (ALPP).	[50]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Alkaline phosphatase, placental type (ALPP).	[52]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Alkaline phosphatase, placental type (ALPP).	[53]
Lithium chloride	DMHYLQ2	Investigative	Lithium chloride increases the activity of Alkaline phosphatase, placental type (ALPP).	[54]
Forskolin	DM6ITNG	Investigative	Forskolin increases the expression of Alkaline phosphatase, placental type (ALPP).	[47]

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