Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTLROA7G)

• DOT Name: Inositol polyphosphate 4-phosphatase type II (INPP4B)
• Synonyms: Type II inositol 3,4-bisphosphate 4-phosphatase; EC 3.1.3.66
• Gene Name: INPP4B
• Related Disease:
  Thyroid gland carcinoma
  Adenocarcinoma
  Advanced cancer
  Bladder cancer
  Breast cancer
  Breast carcinoma
  Cervical cancer
  Cervical carcinoma
  Clear cell renal carcinoma
  Epithelial ovarian cancer
  Hepatocellular carcinoma
  Laryngeal carcinoma
  Lymphoma
  Multiple sclerosis
  Neoplasm
  Ovarian cancer
  Ovarian neoplasm
  Papillary renal cell carcinoma
  Prostate neoplasm
  Renal cell carcinoma
  Thyroid cancer
  Triple negative breast cancer
  Urinary bladder cancer
  Urinary bladder neoplasm
  Carcinoma
  leukaemia
  Leukemia
  Metastatic malignant neoplasm
  Nasopharyngeal carcinoma
  Prostate carcinoma
  Acute myelogenous leukaemia
  Amyotrophic lateral sclerosis type 1
  Bone osteosarcoma
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Lung cancer
  Lung carcinoma
  Melanoma
  Osteosarcoma
  Pancreatic cancer
  Prostate cancer
• UniProt ID: INP4B_HUMAN
• EC Number: 3.1.3.66
• Sequence:
  MEIKEEGASEEGQHFLPTAQANDPGDCQFTSIQKTPNEPQLEFILACKDLVAPVRDRKLN
  TLVQISVIHPVEQSLTRYSSTEIVEGTRDPLFLTGVTFPSEYPIYEETKIKLTVYDVKDK
  SHDTVRTSVLPEHKDPPPEVGRSFLGYASFKVGELLKSKEQLLVLSLRTSDGGKVVGTIE
  VSVVKMGEIEDGEADHITTDVQGQKCALVCECTAPESVSGKDNLPFLNSVLKNPVCKLYR
  FPTSDNKWMRIREQMSESILSFHIPKELISLHIKEDLCRNQEIKELGELSPHWDNLRKNV
  LTHCDQMVNMYQDILTELSKETGSSFKSSSSKGEKTLEFVPINLHLQRMQVHSPHLKDAL
  YDVITVGAPAAHFQGFKNGGLRKLLHRFETERRNTGYQFIYYSPENTAKAKEVLSNINQL
  QPLIATHADLLLNSASQHSPDSLKNSLKMLSEKTELFVHAFKDQLVRSALLALYTARPGG
  ILKKPPSPKSSTEESSPQDQPPVMRGQDSIPHHSDYDEEEWDRVWANVGKSLNCIIAMVD
  KLIERDGGSEGSGGNNDGEKEPSLTDAIPSHPREDWYEQLYPLILTLKDCMGEVVNRAKQ
  SLTFVLLQELAYSLPQCLMLTLRRDIVFSQALAGLVCGFIIKLQTSLYDPGFLQQLHTVG
  LIVQYEGLLSTYSDEIGMLEDMAVGISDLKKVAFKIIEAKSNDVLPVITGRREHYVVEVK
  LPARMFESLPLQIKEGQLLHVYPVLFNVGINEQQTLAERFGDVSLQESINQENFELLQEY
  YKIFMEKMPPDYISHFQEQNDLKALLENLLQNIQSKKRKNVEIMWLAATICRKLNGIRFT
  CCKSAKDRTSMSVTLEQCSILRDEHQLHKDFFIRALDCMRREGCRIENVLKNIKCRKYAF
  NMLQLMAFPKYYRPPEGTYGKADT
• Function: Catalyzes the hydrolysis of the 4-position phosphate of phosphatidylinositol 3,4-bisphosphate, inositol 1,3,4-trisphosphate and inositol 3,4-trisphosphate. Plays a role in the late stages of macropinocytosis by dephosphorylating phosphatidylinositol 3,4-bisphosphate in membrane ruffles. The lipid phosphatase activity is critical for tumor suppressor function. Antagonizes the PI3K-AKT/PKB signaling pathway by dephosphorylating phosphoinositides and thereby modulating cell cycle progression and cell survival.
• Tissue Specificity: Widely expressed with highest levels occurring in the skeletal muscle and heart.
• KEGG Pathway:
  Inositol phosphate metabolism (hsa00562)
  Metabolic pathways (hsa01100)
  Phosphatidylinositol sig.ling system (hsa04070)
• Reactome Pathway:
  Synthesis of PIPs at the early endosome membrane (R-HSA-1660516)
  Synthesis of IP2, IP, and Ins in the cytosol (R-HSA-1855183)
  Synthesis of PIPs at the plasma membrane (R-HSA-1660499)
• BioCyc Pathway: MetaCyc:HS03227-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

42 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Thyroid gland carcinoma	DISMNGZ0	Definitive	Altered Expression	[1]
Adenocarcinoma	DIS3IHTY	Strong	Biomarker	[2]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[3]
Bladder cancer	DISUHNM0	Strong	Altered Expression	[4]
Breast cancer	DIS7DPX1	Strong	Biomarker	[5]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[5]
Cervical cancer	DISFSHPF	Strong	Biomarker	[6]
Cervical carcinoma	DIST4S00	Strong	Biomarker	[6]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[7]
Epithelial ovarian cancer	DIS56MH2	Strong	Genetic Variation	[8]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[9]
Laryngeal carcinoma	DISNHCIV	Strong	Altered Expression	[10]
Lymphoma	DISN6V4S	Strong	Biomarker	[11]
Multiple sclerosis	DISB2WZI	Strong	Genetic Variation	[12]
Neoplasm	DISZKGEW	Strong	Biomarker	[3]
Ovarian cancer	DISZJHAP	Strong	Genetic Variation	[8]
Ovarian neoplasm	DISEAFTY	Strong	Genetic Variation	[8]
Papillary renal cell carcinoma	DIS25HBV	Strong	Biomarker	[7]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[13]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[7]
Thyroid cancer	DIS3VLDH	Strong	Genetic Variation	[14]
Triple negative breast cancer	DISAMG6N	Strong	Altered Expression	[15]
Urinary bladder cancer	DISDV4T7	Strong	Biomarker	[7]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[7]
Carcinoma	DISH9F1N	moderate	Altered Expression	[16]
leukaemia	DISS7D1V	moderate	Biomarker	[17]
Leukemia	DISNAKFL	moderate	Biomarker	[17]
Metastatic malignant neoplasm	DIS86UK6	moderate	Altered Expression	[9]
Nasopharyngeal carcinoma	DISAOTQ0	moderate	Altered Expression	[18]
Prostate carcinoma	DISMJPLE	moderate	Altered Expression	[19]
Acute myelogenous leukaemia	DISCSPTN	Limited	Altered Expression	[20]
Amyotrophic lateral sclerosis type 1	DIS5A2M0	Limited	Genetic Variation	[21]
Bone osteosarcoma	DIST1004	Limited	Altered Expression	[22]
Colon cancer	DISVC52G	Limited	Biomarker	[23]
Colon carcinoma	DISJYKUO	Limited	Biomarker	[23]
Colorectal carcinoma	DIS5PYL0	Limited	Biomarker	[24]
Lung cancer	DISCM4YA	Limited	Biomarker	[25]
Lung carcinoma	DISTR26C	Limited	Biomarker	[25]
Melanoma	DIS1RRCY	Limited	Biomarker	[23]
Osteosarcoma	DISLQ7E2	Limited	Altered Expression	[22]
Pancreatic cancer	DISJC981	Limited	Biomarker	[26]
Prostate cancer	DISF190Y	Limited	Altered Expression	[19]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Daunorubicin	DMQUSBT	Approved	Inositol polyphosphate 4-phosphatase type II (INPP4B) affects the response to substance of Daunorubicin.	[52]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Inositol polyphosphate 4-phosphatase type II (INPP4B).	[27]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Inositol polyphosphate 4-phosphatase type II (INPP4B).	[33]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Inositol polyphosphate 4-phosphatase type II (INPP4B).	[46]

22 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 Inositol polyphosphate 4-phosphatase type II (INPP4B).	[28]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Inositol polyphosphate 4-phosphatase type II (INPP4B).	[29]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Inositol polyphosphate 4-phosphatase type II (INPP4B).	[30]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Inositol polyphosphate 4-phosphatase type II (INPP4B).	[31]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Inositol polyphosphate 4-phosphatase type II (INPP4B).	[32]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Inositol polyphosphate 4-phosphatase type II (INPP4B).	[34]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Inositol polyphosphate 4-phosphatase type II (INPP4B).	[35]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Inositol polyphosphate 4-phosphatase type II (INPP4B).	[36]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Inositol polyphosphate 4-phosphatase type II (INPP4B).	[37]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Inositol polyphosphate 4-phosphatase type II (INPP4B).	[38]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Inositol polyphosphate 4-phosphatase type II (INPP4B).	[39]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Inositol polyphosphate 4-phosphatase type II (INPP4B).	[40]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Inositol polyphosphate 4-phosphatase type II (INPP4B).	[41]
Seocalcitol	DMKL9QO	Phase 3	Seocalcitol increases the expression of Inositol polyphosphate 4-phosphatase type II (INPP4B).	[42]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Inositol polyphosphate 4-phosphatase type II (INPP4B).	[43]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Inositol polyphosphate 4-phosphatase type II (INPP4B).	[44]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Inositol polyphosphate 4-phosphatase type II (INPP4B).	[45]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Inositol polyphosphate 4-phosphatase type II (INPP4B).	[47]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Inositol polyphosphate 4-phosphatase type II (INPP4B).	[48]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Inositol polyphosphate 4-phosphatase type II (INPP4B).	[49]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Inositol polyphosphate 4-phosphatase type II (INPP4B).	[50]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate decreases the expression of Inositol polyphosphate 4-phosphatase type II (INPP4B).	[51]

References

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• [4] Estrogen receptor alpha prevents bladder cancer via INPP4B inhibited akt pathway in vitro and in vivo.Oncotarget. 2014 Sep 15;5(17):7917-35. doi: 10.18632/oncotarget.1421.
• [5] miR-181 elevates Akt signaling by co-targeting PHLPP2 and INPP4B phosphatases in luminal breast cancer.Int J Cancer. 2017 May 15;140(10):2310-2320. doi: 10.1002/ijc.30661. Epub 2017 Mar 11.
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• [25] miR-937 contributes to the lung cancer cell proliferation by targeting INPP4B.Life Sci. 2016 Jun 15;155:110-5. doi: 10.1016/j.lfs.2016.05.014. Epub 2016 May 12.
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