Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5U41ZP)

• DOT Name: Homeobox protein MSX-1 (MSX1)
• Synonyms: Homeobox protein Hox-7; Msh homeobox 1-like protein
• Gene Name: MSX1
• Related Disease:
  Breast cancer
  Breast carcinoma
  Classic Hodgkin lymphoma
  Orofacial cleft 5
  Tooth agenesis, selective, 1
  Acute myelogenous leukaemia
  Adenoma
  Advanced cancer
  Atrial septal defect
  Autism spectrum disorder
  Barrett esophagus
  Breast neoplasm
  Cervical cancer
  Cervical carcinoma
  Childhood acute lymphoblastic leukemia
  Cleft lip
  Cleft lip/palate
  Cleft palate
  Colorectal carcinoma
  Epithelial ovarian cancer
  Esophageal adenocarcinoma
  Huntington disease
  Isolated cleft lip
  Isolated cleft palate
  leukaemia
  Leukemia
  Mantle cell lymphoma
  Neoplasm
  Orofacial cleft
  Ovarian cancer
  Ovarian neoplasm
  Plasma cell myeloma
  Stomach cancer
  T-cell acute lymphoblastic leukaemia
  T-cell lymphoma
  Wolf-Hirschhorn syndrome
  Adult glioblastoma
  Chronic obstructive pulmonary disease
  Glioblastoma multiforme
  Tooth agenesis
  Tooth and nail syndrome
  Childhood kidney Wilms tumor
  Congenital heart disease
  Cryptorchidism
  Gastric cancer
  Gastric neoplasm
  Hereditary diffuse gastric adenocarcinoma
  Melanoma
  Neuroblastoma
  Wilms tumor
• UniProt ID: MSX1_HUMAN
• Pfam ID: PF00046
• Sequence:
  MAPAADMTSLPLGVKVEDSAFGKPAGGGAGQAPSAAAATAAAMGADEEGAKPKVSPSLLP
  FSVEALMADHRKPGAKESALAPSEGVQAAGGSAQPLGVPPGSLGAPDAPSSPRPLGHFSV
  GGLLKLPEDALVKAESPEKPERTPWMQSPRFSPPPARRLSPPACTLRKHKTNRKPRTPFT
  TAQLLALERKFRQKQYLSIAERAEFSSSLSLTETQVKIWFQNRRAKAKRLQEAELEKLKM
  AAKPMLPPAAFGLSFPLGGPAAVAAAAGASLYGASGPFQRAALPVAPVGLYTAHVGYSMY
  HLT
• Function: Acts as a transcriptional repressor. Capable of transcription autoinactivation. Binds to the consensus sequence 5'-C/GTAAT-3' in downstream activin regulatory elements (DARE) in the gene promoter, thereby repressing the transcription of CGA/alpha-GSU and GNRHR. Represses transcription of myoblast differentiation factors. Binds to core enhancer regions in target gene promoters of myoblast differentiation factors with binding specificity facilitated by interaction with PIAS1. Recruits histone H3 methyltransferases such as EHMT2/G9a to gene promoter regions which leads to inhibition of myoblast differentiation via transcriptional repression of differentiation factors. Regulates, in a stage-specific manner, a developmental program of gene expression in the fetal tooth bud that controls odontoblast differentiation and proliferation of dental mesenchymal cells. At the bud stage, required for mesenchymal molar tooth bud development via facilitating reciprocal signaling between dental epithelial and mesenchymal cells. May also regulate expression of Wnt antagonists such as DKK2 and SFPR2 in the developing tooth mesenchyme. Required for BMP4 expression in dental mesenchyme cells. Also, in response to BMP4, required for BMP4 expression in neighboring dental epithelial cells. Required for maximal FGF4-induced expression of SDC1 in dental mesenchyme cells. Also in response to SDC1, required for SDC1 expression in neighboring dental epithelial cells. At the early bell stage, acts to drive proliferation of dental mesenchyme cells, however during the late bell stage acts as an homeostatic regulator of the cell cycle. Regulates proliferation and inhibits premature mesenchymal odontogenesis during the bell stage via inhibition of the Wnt signaling component CTNNB1 and subsequent repression of the odontoblast differentiation factors BMP2, BMP4, LEF1, ALPL and BGLAP/OCN. Additionally, required for correct development and fusion of the palatal shelves and embryonic mandibular formation. Plays a role in embryonic bone formation of the middle ear, skull and nasal bones. Required for correct formation and thickness of the nail plate. May play a role in limb-pattern formation.
• KEGG Pathway: Human T-cell leukemia virus 1 infection (hsa05166)

Molecular Interaction Atlas (MIA) of This DOT

50 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Definitive	Posttranslational Modification	[1]
Breast carcinoma	DIS2UE88	Definitive	Posttranslational Modification	[1]
Classic Hodgkin lymphoma	DISV1LU6	Definitive	Genetic Variation	[2]
Orofacial cleft 5	DISXH76T	Definitive	Autosomal dominant	[3]
Tooth agenesis, selective, 1	DIS84ERL	Definitive	Autosomal dominant	[4]
Acute myelogenous leukaemia	DISCSPTN	Strong	Altered Expression	[5]
Adenoma	DIS78ZEV	Strong	Altered Expression	[6]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Atrial septal defect	DISJT76B	Strong	Biomarker	[7]
Autism spectrum disorder	DISXK8NV	Strong	Genetic Variation	[8]
Barrett esophagus	DIS416Y7	Strong	Genetic Variation	[9]
Breast neoplasm	DISNGJLM	Strong	Posttranslational Modification	[1]
Cervical cancer	DISFSHPF	Strong	Biomarker	[10]
Cervical carcinoma	DIST4S00	Strong	Biomarker	[10]
Childhood acute lymphoblastic leukemia	DISJ5D6U	Strong	Biomarker	[11]
Cleft lip	DISV3XW6	Strong	Biomarker	[12]
Cleft lip/palate	DIS14IG3	Strong	Genetic Variation	[13]
Cleft palate	DIS6G5TF	Strong	Genetic Variation	[14]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[15]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[16]
Esophageal adenocarcinoma	DISODWFP	Strong	Genetic Variation	[9]
Huntington disease	DISQPLA4	Strong	Genetic Variation	[17]
Isolated cleft lip	DIS2O2JV	Strong	Biomarker	[12]
Isolated cleft palate	DISV80CD	Strong	Genetic Variation	[14]
leukaemia	DISS7D1V	Strong	Biomarker	[11]
Leukemia	DISNAKFL	Strong	Biomarker	[11]
Mantle cell lymphoma	DISFREOV	Strong	Altered Expression	[5]
Neoplasm	DISZKGEW	Strong	Altered Expression	[15]
Orofacial cleft	DIST1HG6	Strong	Biomarker	[18]
Ovarian cancer	DISZJHAP	Strong	Altered Expression	[16]
Ovarian neoplasm	DISEAFTY	Strong	Altered Expression	[16]
Plasma cell myeloma	DIS0DFZ0	Strong	Biomarker	[19]
Stomach cancer	DISKIJSX	Strong	Biomarker	[20]
T-cell acute lymphoblastic leukaemia	DIS17AI2	Strong	Biomarker	[21]
T-cell lymphoma	DISSXRTQ	Strong	Biomarker	[22]
Wolf-Hirschhorn syndrome	DISE4WMQ	Strong	Genetic Variation	[23]
Adult glioblastoma	DISVP4LU	moderate	Biomarker	[24]
Chronic obstructive pulmonary disease	DISQCIRF	moderate	Biomarker	[25]
Glioblastoma multiforme	DISK8246	moderate	Biomarker	[24]
Tooth agenesis	DIS1PWC7	Supportive	Autosomal dominant	[26]
Tooth and nail syndrome	DISXBBN3	Supportive	Autosomal dominant	[27]
Childhood kidney Wilms tumor	DIS0NMK3	Limited	Biomarker	[28]
Congenital heart disease	DISQBA23	Limited	Genetic Variation	[29]
Cryptorchidism	DISYUD2P	Limited	Biomarker	[30]
Gastric cancer	DISXGOUK	Limited	Biomarker	[20]
Gastric neoplasm	DISOKN4Y	Limited	Biomarker	[31]
Hereditary diffuse gastric adenocarcinoma	DISUIBYS	Limited	Biomarker	[31]
Melanoma	DIS1RRCY	Limited	Biomarker	[32]
Neuroblastoma	DISVZBI4	Limited	Biomarker	[33]
Wilms tumor	DISB6T16	Limited	Biomarker	[28]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Homeobox protein MSX-1 (MSX1).	[34]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Homeobox protein MSX-1 (MSX1).	[35]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Homeobox protein MSX-1 (MSX1).	[36]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Homeobox protein MSX-1 (MSX1).	[37]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Homeobox protein MSX-1 (MSX1).	[38]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Homeobox protein MSX-1 (MSX1).	[39]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Homeobox protein MSX-1 (MSX1).	[40]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Homeobox protein MSX-1 (MSX1).	[42]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Homeobox protein MSX-1 (MSX1).	[43]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Homeobox protein MSX-1 (MSX1).	[44]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Homeobox protein MSX-1 (MSX1).	[45]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Homeobox protein MSX-1 (MSX1).	[31]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Homeobox protein MSX-1 (MSX1).	[47]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Homeobox protein MSX-1 (MSX1).	[44]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of Homeobox protein MSX-1 (MSX1).	[48]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of Homeobox protein MSX-1 (MSX1).	[49]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Homeobox protein MSX-1 (MSX1).	[50]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Homeobox protein MSX-1 (MSX1).	[51]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Homeobox protein MSX-1 (MSX1).	[44]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Homeobox protein MSX-1 (MSX1).	[44]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Homeobox protein MSX-1 (MSX1).	[52]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Homeobox protein MSX-1 (MSX1).	[55]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Homeobox protein MSX-1 (MSX1).	[56]
SC-560	DMT1GJL	Investigative	SC-560 decreases the expression of Homeobox protein MSX-1 (MSX1).	[57]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic increases the methylation of Homeobox protein MSX-1 (MSX1).	[41]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Homeobox protein MSX-1 (MSX1).	[53]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Homeobox protein MSX-1 (MSX1).	[54]

References

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