Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1WDKE1)

• DOT Name: Homeobox protein MSX-2 (MSX2)
• Synonyms: Homeobox protein Hox-8
• Gene Name: MSX2
• Related Disease:
  Craniosynostosis 2
  Parietal foramina
  Parietal foramina with cleidocranial dysplasia
  Syndactyly
  Advanced cancer
  B-cell neoplasm
  Bone osteosarcoma
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Cervical cancer
  Cervical carcinoma
  Cholangiocarcinoma
  Chronic pancreatitis
  Colon cancer
  Colon carcinoma
  Congenital deformities of limbs
  Congestive heart failure
  Diabetic kidney disease
  Gastric cancer
  Kidney failure
  Liver cirrhosis
  Matthew-Wood syndrome
  Melanoma
  Nasal polyp
  Neoplasm
  Neural tube defect
  Osteosarcoma
  Pancreatic cancer
  Pancreatic tumour
  Parietal foramina 1
  Partial trisomy of the long arm of chromosome 5
  Stomach cancer
  Synostosis
  Tuberculosis
  Coronary atherosclerosis
  Myocardial ischemia
  High blood pressure
  Potocki-Shaffer syndrome
  Ankylosing spondylitis
  Atrial septal defect
  Autism spectrum disorder
  Chronic kidney disease
  Colorectal carcinoma
  Non-insulin dependent diabetes
  Patent ductus arteriosus
  Periodontitis
  T-cell acute lymphoblastic leukaemia
  Type-1/2 diabetes
• UniProt ID: MSX2_HUMAN
• Pfam ID: PF00046
• Sequence:
  MASPSKGNDLFSPDEEGPAVVAGPGPGPGGAEGAAEERRVKVSSLPFSVEALMSDKKPPK
  EASPLPAESASAGATLRPLLLSGHGAREAHSPGPLVKPFETASVKSENSEDGAAWMQEPG
  RYSPPPRHMSPTTCTLRKHKTNRKPRTPFTTSQLLALERKFRQKQYLSIAERAEFSSSLN
  LTETQVKIWFQNRRAKAKRLQEAELEKLKMAAKPMLPSSFSLPFPISSPLQAASIYGASY
  PFHRPVLPIPPVGLYATPVGYGMYHLS
• Function: Acts as a transcriptional regulator in bone development. Represses the ALPL promoter activity and antagonizes the stimulatory effect of DLX5 on ALPL expression during osteoblast differentiation. Probable morphogenetic role. May play a role in limb-pattern formation. In osteoblasts, suppresses transcription driven by the osteocalcin FGF response element (OCFRE). Binds to the homeodomain-response element of the ALPL promoter.
• KEGG Pathway: Human T-cell leukemia virus 1 infection (hsa05166)
• Reactome Pathway: Regulation of RUNX2 expression and activity (R-HSA-8939902)

Molecular Interaction Atlas (MIA) of This DOT

49 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Craniosynostosis 2	DISBJX9D	Definitive	Autosomal dominant	[1]
Parietal foramina	DISS1N5X	Definitive	Autosomal dominant	[1]
Parietal foramina with cleidocranial dysplasia	DISDH5AG	Definitive	Autosomal dominant	[2]
Syndactyly	DISZK2BT	Definitive	Altered Expression	[3]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[4]
B-cell neoplasm	DISVY326	Strong	Biomarker	[5]
Bone osteosarcoma	DIST1004	Strong	Biomarker	[6]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[7]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[7]
Breast neoplasm	DISNGJLM	Strong	Altered Expression	[7]
Cervical cancer	DISFSHPF	Strong	Altered Expression	[8]
Cervical carcinoma	DIST4S00	Strong	Altered Expression	[8]
Cholangiocarcinoma	DIS71F6X	Strong	Altered Expression	[9]
Chronic pancreatitis	DISBUOMJ	Strong	Altered Expression	[10]
Colon cancer	DISVC52G	Strong	Biomarker	[11]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[11]
Congenital deformities of limbs	DISP4N1Q	Strong	Biomarker	[12]
Congestive heart failure	DIS32MEA	Strong	Genetic Variation	[13]
Diabetic kidney disease	DISJMWEY	Strong	Biomarker	[14]
Gastric cancer	DISXGOUK	Strong	Genetic Variation	[15]
Kidney failure	DISOVQ9P	Strong	Altered Expression	[16]
Liver cirrhosis	DIS4G1GX	Strong	Altered Expression	[17]
Matthew-Wood syndrome	DISA7HR7	Strong	Altered Expression	[10]
Melanoma	DIS1RRCY	Strong	Biomarker	[18]
Nasal polyp	DISLP3XE	Strong	Biomarker	[19]
Neoplasm	DISZKGEW	Strong	Biomarker	[20]
Neural tube defect	DIS5J95E	Strong	Genetic Variation	[21]
Osteosarcoma	DISLQ7E2	Strong	Biomarker	[6]
Pancreatic cancer	DISJC981	Strong	Altered Expression	[22]
Pancreatic tumour	DIS3U0LK	Strong	Altered Expression	[23]
Parietal foramina 1	DISQHJZI	Strong	Autosomal dominant	[24]
Partial trisomy of the long arm of chromosome 5	DISFHG81	Strong	Biomarker	[25]
Stomach cancer	DISKIJSX	Strong	Genetic Variation	[15]
Synostosis	DISXGMZW	Strong	Biomarker	[26]
Tuberculosis	DIS2YIMD	Strong	Biomarker	[27]
Coronary atherosclerosis	DISKNDYU	moderate	Biomarker	[28]
Myocardial ischemia	DISFTVXF	moderate	Biomarker	[28]
High blood pressure	DISY2OHH	Disputed	Biomarker	[29]
Potocki-Shaffer syndrome	DISKGU59	Disputed	Biomarker	[30]
Ankylosing spondylitis	DISRC6IR	Limited	Genetic Variation	[31]
Atrial septal defect	DISJT76B	Limited	Biomarker	[32]
Autism spectrum disorder	DISXK8NV	Limited	Biomarker	[32]
Chronic kidney disease	DISW82R7	Limited	Biomarker	[33]
Colorectal carcinoma	DIS5PYL0	Limited	Biomarker	[34]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Biomarker	[33]
Patent ductus arteriosus	DIS9P8YS	Limited	Biomarker	[35]
Periodontitis	DISI9JOI	Limited	Biomarker	[36]
T-cell acute lymphoblastic leukaemia	DIS17AI2	Limited	Altered Expression	[37]
Type-1/2 diabetes	DISIUHAP	Limited	Altered Expression	[34]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic trioxide	DM61TA4	Approved	Homeobox protein MSX-2 (MSX2) decreases the response to substance of Arsenic trioxide.	[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 Homeobox protein MSX-2 (MSX2).	[38]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Homeobox protein MSX-2 (MSX2).	[46]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Homeobox protein MSX-2 (MSX2).	[50]

14 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 Homeobox protein MSX-2 (MSX2).	[39]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Homeobox protein MSX-2 (MSX2).	[40]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Homeobox protein MSX-2 (MSX2).	[41]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Homeobox protein MSX-2 (MSX2).	[42]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Homeobox protein MSX-2 (MSX2).	[43]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Homeobox protein MSX-2 (MSX2).	[44]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Homeobox protein MSX-2 (MSX2).	[45]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Homeobox protein MSX-2 (MSX2).	[45]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Homeobox protein MSX-2 (MSX2).	[45]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Homeobox protein MSX-2 (MSX2).	[47]
GSK2816126	DMJDVW4	Phase 1	GSK2816126 increases the expression of Homeobox protein MSX-2 (MSX2).	[48]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Homeobox protein MSX-2 (MSX2).	[49]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Homeobox protein MSX-2 (MSX2).	[51]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Homeobox protein MSX-2 (MSX2).	[41]

References

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