Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTZK5G8)

• DOT Name: Paired mesoderm homeobox protein 1 (PRRX1)
• Synonyms: Homeobox protein PHOX1; Paired-related homeobox protein 1; PRX-1
• Gene Name: PRRX1
• Related Disease:
  Matthew-Wood syndrome
  Non-small-cell lung cancer
  Parkinson disease
  Subarachnoid hemorrhage
  Alzheimer disease
  Arteriosclerosis
  Atherosclerosis
  Beta-thalassemia major
  Breast cancer
  Breast carcinoma
  Carcinoma of esophagus
  Chronic graft versus host disease
  Colorectal carcinoma
  Craniosynostosis
  Esophageal cancer
  Hamartoma
  Head-neck squamous cell carcinoma
  Hepatocellular carcinoma
  High blood pressure
  leukaemia
  Leukemia
  Liver cirrhosis
  Myeloid leukaemia
  Neoplasm
  Neoplasm of esophagus
  Non-insulin dependent diabetes
  Obesity
  Pancreatic cancer
  Pick disease
  Prostate cancer
  Prostate neoplasm
  Squamous cell carcinoma
  Triple negative breast cancer
  Atrial fibrillation
  Familial atrial fibrillation
  Osteoarthritis
  Agnathia-otocephaly complex
  Acute myelogenous leukaemia
  Advanced cancer
  Carcinoma of liver and intrahepatic biliary tract
  Clear cell renal carcinoma
  Liver cancer
  Tuberous sclerosis
• UniProt ID: PRRX1_HUMAN
• Pfam ID: PF00046 ; PF03826
• Sequence:
  MTSSYGHVLERQPALGGRLDSPGNLDTLQAKKNFSVSHLLDLEEAGDMVAAQADENVGEA
  GRSLLESPGLTSGSDTPQQDNDQLNSEEKKKRKQRRNRTTFNSSQLQALERVFERTHYPD
  AFVREDLARRVNLTEARVQVWFQNRRAKFRRNERAMLANKNASLLKSYSGDVTAVEQPIV
  PRPAPRPTDYLSWGTASPYSAMATYSATCANNSPAQGINMANSIANLRLKAKEYSLQRNQ
  VPTVN
• Function: Master transcription factor of stromal fibroblasts for myofibroblastic lineage progression. Orchestrates the functional drift of fibroblasts into myofibroblastic phenotype via TGF-beta signaling by remodeling a super-enhancer landscape. Through this function, plays an essential role in wound healing process. Acts as a transcriptional regulator of muscle creatine kinase (MCK) and so has a role in the establishment of diverse mesodermal muscle types. The protein binds to an A/T-rich element in the muscle creatine enhancer. May play a role in homeostasis and regeneration of bone, white adipose tissue and derm; [Isoform 1]: Transcriptional activator, when transfected in fibroblastic or myoblastic cell lines. This activity may be masked by the C-terminal OAR domain; [Isoform 2]: Transcriptional repressor, when transfected in fibroblastic or myoblastic cell lines.
• Tissue Specificity: .Widely expressed in embryonic and adult tissues, with highest levels in skeletal muscle. Isoform 1 is either expressed at similar or higher levels compared to isoform 2 in all embryonic tissues but skeletal muscle and heart. In adult tissues, expressed at lower levels compared to isoform 2.; [Isoform 2]: Widely expressed in embryonic and adult tissues, with highest levels in skeletal muscle. Isoform 2 is either expressed at similar or lower levels compared to isoform 1 in all embryonic tissues but skeletal muscle and heart, where it is expressed at higher levels. In adult tissues, expressed at higher levels compared to isoform 1.

Molecular Interaction Atlas (MIA) of This DOT

43 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Matthew-Wood syndrome	DISA7HR7	Definitive	Biomarker	[1]
Non-small-cell lung cancer	DIS5Y6R9	Definitive	Altered Expression	[2]
Parkinson disease	DISQVHKL	Definitive	Altered Expression	[3]
Subarachnoid hemorrhage	DISI7I8Y	Definitive	Altered Expression	[4]
Alzheimer disease	DISF8S70	Strong	Biomarker	[5]
Arteriosclerosis	DISK5QGC	Strong	Altered Expression	[6]
Atherosclerosis	DISMN9J3	Strong	Altered Expression	[6]
Beta-thalassemia major	DISW06BV	Strong	Biomarker	[7]
Breast cancer	DIS7DPX1	Strong	Genetic Variation	[8]
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[8]
Carcinoma of esophagus	DISS6G4D	Strong	Biomarker	[9]
Chronic graft versus host disease	DIS1MM9J	Strong	Biomarker	[10]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[11]
Craniosynostosis	DIS6J405	Strong	Genetic Variation	[12]
Esophageal cancer	DISGB2VN	Strong	Biomarker	[9]
Hamartoma	DIS0I87H	Strong	Biomarker	[13]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Biomarker	[14]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[15]
High blood pressure	DISY2OHH	Strong	Genetic Variation	[16]
leukaemia	DISS7D1V	Strong	Biomarker	[17]
Leukemia	DISNAKFL	Strong	Biomarker	[17]
Liver cirrhosis	DIS4G1GX	Strong	Biomarker	[18]
Myeloid leukaemia	DISMN944	Strong	Biomarker	[17]
Neoplasm	DISZKGEW	Strong	Biomarker	[14]
Neoplasm of esophagus	DISOLKAQ	Strong	Biomarker	[9]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Genetic Variation	[19]
Obesity	DIS47Y1K	Strong	Altered Expression	[20]
Pancreatic cancer	DISJC981	Strong	Biomarker	[1]
Pick disease	DISP6X50	Strong	Altered Expression	[21]
Prostate cancer	DISF190Y	Strong	Biomarker	[22]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[22]
Squamous cell carcinoma	DISQVIFL	Strong	Biomarker	[23]
Triple negative breast cancer	DISAMG6N	Strong	Biomarker	[24]
Atrial fibrillation	DIS15W6U	moderate	Genetic Variation	[25]
Familial atrial fibrillation	DISL4AGF	moderate	Biomarker	[26]
Osteoarthritis	DIS05URM	moderate	Genetic Variation	[27]
Agnathia-otocephaly complex	DISFA33B	Supportive	Autosomal dominant	[28]
Acute myelogenous leukaemia	DISCSPTN	Limited	Genetic Variation	[29]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[14]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Limited	Altered Expression	[30]
Clear cell renal carcinoma	DISBXRFJ	Limited	Altered Expression	[31]
Liver cancer	DISDE4BI	Limited	Altered Expression	[30]
Tuberous sclerosis	DISEMUGZ	Limited	Biomarker	[32]

20 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 Paired mesoderm homeobox protein 1 (PRRX1).	[33]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Paired mesoderm homeobox protein 1 (PRRX1).	[34]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Paired mesoderm homeobox protein 1 (PRRX1).	[35]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Paired mesoderm homeobox protein 1 (PRRX1).	[36]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Paired mesoderm homeobox protein 1 (PRRX1).	[37]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Paired mesoderm homeobox protein 1 (PRRX1).	[38]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Paired mesoderm homeobox protein 1 (PRRX1).	[39]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Paired mesoderm homeobox protein 1 (PRRX1).	[40]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Paired mesoderm homeobox protein 1 (PRRX1).	[41]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Paired mesoderm homeobox protein 1 (PRRX1).	[42]
Indomethacin	DMSC4A7	Approved	Indomethacin decreases the expression of Paired mesoderm homeobox protein 1 (PRRX1).	[41]
Rofecoxib	DM3P5DA	Approved	Rofecoxib affects the expression of Paired mesoderm homeobox protein 1 (PRRX1).	[43]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Paired mesoderm homeobox protein 1 (PRRX1).	[42]
Fenretinide	DMRD5SP	Phase 3	Fenretinide increases the expression of Paired mesoderm homeobox protein 1 (PRRX1).	[44]
PD-0325901	DM27D4J	Phase 2	PD-0325901 decreases the expression of Paired mesoderm homeobox protein 1 (PRRX1).	[45]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Paired mesoderm homeobox protein 1 (PRRX1).	[47]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Paired mesoderm homeobox protein 1 (PRRX1).	[48]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Paired mesoderm homeobox protein 1 (PRRX1).	[49]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate decreases the expression of Paired mesoderm homeobox protein 1 (PRRX1).	[50]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID decreases the expression of Paired mesoderm homeobox protein 1 (PRRX1).	[51]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Paired mesoderm homeobox protein 1 (PRRX1).	[46]

References

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