Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZD5099)

• DOT Name: Microtubule-associated protein 9 (MAP9)
• Synonyms: Aster-associated protein
• Gene Name: MAP9
• Related Disease:
  Cone-rod dystrophy
  Cone-rod dystrophy 2
  Advanced cancer
  Astrocytoma
  Breast cancer
  Colorectal neoplasm
  High blood pressure
  Obesity
  Obstructive sleep apnea
  Osteoporosis
  Postmenopausal osteoporosis
  Prostate cancer
  Prostate carcinoma
  Stroke
  Colorectal carcinoma
  Intestinal neoplasm
  Neoplasm
• UniProt ID: MAP9_HUMAN
• Sequence:
  MSDEVFSTTLAYTKSPKVTKRTTFQDELIRAITARSARQRSSEYSDDFDSDEIVSLGDFS
  DTSADENSVNKKMNDFHISDDEEKNPSKLLFLKTNKSNGNITKDEPVCAIKNEEEMAPDG
  CEDIVVKSFSESQNKDEEFEKDKIKMKPKPRILSIKSTSSAENNSLDTDDHFKPSPRPRS
  MLKKKSHMEEKDGLEDKETALSEELELHSAPSSLPTPNGIQLEAEKKAFSENLDPEDSCL
  TSLASSSLKQILGDSFSPGSEGNASGKDPNEEITENHNSLKSDENKENSFSADHVTTAVE
  KSKESQVTADDLEEEKAKAELIMDDDRTVDPLLSKSQSILISTSATASSKKTIEDRNIKN
  KKSTNNRASSASARLMTSEFLKKSSSKRRTPSTTTSSHYLGTLKVLDQKPSQKQSIEPDR
  ADNIRAAVYQEWLEKKNVYLHEMHRIKRIESENLRIQNEQKKAAKREEALASFEAWKAMK
  EKEAKKIAAKKRLEEKNKKKTEEENAARKGEALQAFEKWKEKKMEYLKEKNRKEREYERA
  KKQKEEETVAEKKKDNLTAVEKWNEKKEAFFKQKEKEKINEKRKEELKRAEKKDKDKQAI
  NEYEKWLENKEKQERIERKQKKRHSFLESEALPPWSPPSRTVFAKVF
• Function: Involved in organization of the bipolar mitotic spindle. Required for bipolar spindle assembly, mitosis progression and cytokinesis. May act by stabilizing interphase microtubules.

Molecular Interaction Atlas (MIA) of This DOT

17 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cone-rod dystrophy	DISY9RWN	Definitive	Genetic Variation	[1]
Cone-rod dystrophy 2	DISX2RWY	Definitive	Genetic Variation	[1]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[2]
Astrocytoma	DISL3V18	Strong	Biomarker	[3]
Breast cancer	DIS7DPX1	Strong	Biomarker	[2]
Colorectal neoplasm	DISR1UCN	Strong	Biomarker	[2]
High blood pressure	DISY2OHH	Strong	Genetic Variation	[4]
Obesity	DIS47Y1K	Strong	Biomarker	[5]
Obstructive sleep apnea	DIS0SVD1	Strong	Biomarker	[4]
Osteoporosis	DISF2JE0	Strong	Biomarker	[6]
Postmenopausal osteoporosis	DISS0RQZ	Strong	Biomarker	[6]
Prostate cancer	DISF190Y	Strong	Biomarker	[7]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[7]
Stroke	DISX6UHX	Strong	Biomarker	[8]
Colorectal carcinoma	DIS5PYL0	moderate	Genetic Variation	[9]
Intestinal neoplasm	DISK0GUH	moderate	Biomarker	[9]
Neoplasm	DISZKGEW	Limited	Biomarker	[9]

9 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 Microtubule-associated protein 9 (MAP9).	[10]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Microtubule-associated protein 9 (MAP9).	[11]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Microtubule-associated protein 9 (MAP9).	[12]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Microtubule-associated protein 9 (MAP9).	[13]
Clorgyline	DMCEUJD	Approved	Clorgyline increases the expression of Microtubule-associated protein 9 (MAP9).	[14]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Microtubule-associated protein 9 (MAP9).	[15]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Microtubule-associated protein 9 (MAP9).	[16]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Microtubule-associated protein 9 (MAP9).	[17]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Microtubule-associated protein 9 (MAP9).	[20]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Microtubule-associated protein 9 (MAP9).	[18]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Microtubule-associated protein 9 (MAP9).	[19]

References

• [1] Variabilities in retinal function and structure in a canine model of cone-rod dystrophy associated with RPGRIP1 support multigenic etiology.Sci Rep. 2017 Oct 9;7(1):12823. doi: 10.1038/s41598-017-13112-w.
• [2] Expression of the microtubule-associated protein MAP9/ASAP and its partners AURKA and PLK1 in colorectal and breast cancers.Dis Markers. 2014;2014:798170. doi: 10.1155/2014/798170. Epub 2014 Apr 30.
• [3] Differential Effects of Doxazosin on Renin-Angiotensin-System- Regulating Aminopeptidase Activities in Neuroblastoma and Glioma Tumoral Cells.CNS Neurol Disord Drug Targets. 2019;18(1):29-36. doi: 10.2174/1871527317666181029111739.
• [4] Auto positive airway pressure therapy reduces pulmonary pressures in adults admitted for acute heart failure with pulmonary hypertension and obstructive sleep apnea. The ASAP-HF Pilot Trial.Sleep. 2019 Jul 8;42(7):zsz100. doi: 10.1093/sleep/zsz100.
• [5] Long-term supplementation of decaffeinated green tea extract does not modify body weight or abdominal obesity in a randomized trial of men at high risk for prostate cancer.Oncotarget. 2017 Jun 29;8(58):99093-99103. doi: 10.18632/oncotarget.18858. eCollection 2017 Nov 17.
• [6] MiR-320a was highly expressed in postmenopausal osteoporosis and acts as a negative regulator in MC3T3E1 cells by reducing MAP9 and inhibiting PI3K/AKT signaling pathway.Exp Mol Pathol. 2019 Oct;110:104282. doi: 10.1016/j.yexmp.2019.104282. Epub 2019 Jul 10.
• [7] Active surveillance outcomes in prostate cancer patients: the use of transperineal template-guided mapping biopsy for patient selection.World J Urol. 2020 Feb;38(2):361-369. doi: 10.1007/s00345-019-02695-w. Epub 2019 Apr 24.
• [8] Propensity-Matched Comparison of OralAnticoagulation Versus Antiplatelet Therapy After Left Atrial Appendage Closure With WATCHMAN.JACC Cardiovasc Interv. 2019 Jun 10;12(11):1055-1063. doi: 10.1016/j.jcin.2019.04.004.
• [9] MAP9 Loss Triggers Chromosomal Instability, Initiates Colorectal Tumorigenesis, and Is Associated with Poor Survival of Patients with Colorectal Cancer.Clin Cancer Res. 2020 Feb 1;26(3):746-757. doi: 10.1158/1078-0432.CCR-19-1611. Epub 2019 Oct 29.
• [10] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [11] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [12] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [13] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [14] Anti-oncogenic and pro-differentiation effects of clorgyline, a monoamine oxidase A inhibitor, on high grade prostate cancer cells. BMC Med Genomics. 2009 Aug 20;2:55. doi: 10.1186/1755-8794-2-55.
• [15] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [16] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [17] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [18] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [19] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [20] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.