Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTN4YLYR)

• DOT Name: Tropomyosin alpha-4 chain (TPM4)
• Synonyms: TM30p1; Tropomyosin-4
• Gene Name: TPM4
• Related Disease:
  Advanced cancer
  Asbestosis
  Chronic idiopathic urticaria
  Colon cancer
  Colon carcinoma
  Dengue
  Epithelial ovarian cancer
  Esophageal cancer
  Esophageal squamous cell carcinoma
  Invasive ductal breast carcinoma
  Lung cancer
  Lung carcinoma
  Neoplasm
  Neoplasm of esophagus
  Non-insulin dependent diabetes
  Ovarian cancer
  Ovarian neoplasm
  Precancerous condition
  Type-1/2 diabetes
  Inherited bleeding disorder, platelet-type
  Malignant soft tissue neoplasm
  Sarcoma
  TPM4-related platelet disorder
  Autosomal dominant macrothrombocytopenia
  Acute coronary syndrome
  Osteoporosis
  Squamous cell carcinoma
• UniProt ID: TPM4_HUMAN
• Pfam ID: PF00261
• Sequence:
  MAGLNSLEAVKRKIQALQQQADEAEDRAQGLQRELDGERERREKAEGDVAALNRRIQLVE
  EELDRAQERLATALQKLEEAEKAADESERGMKVIENRAMKDEEKMEIQEMQLKEAKHIAE
  EADRKYEEVARKLVILEGELERAEERAEVSELKCGDLEEELKNVTNNLKSLEAASEKYSE
  KEDKYEEEIKLLSDKLKEAETRAEFAERTVAKLEKTIDDLEEKLAQAKEENVGLHQTLDQ
  TLNELNCI
• Function: Binds to actin filaments in muscle and non-muscle cells. Plays a central role, in association with the troponin complex, in the calcium dependent regulation of vertebrate striated muscle contraction. Smooth muscle contraction is regulated by interaction with caldesmon. In non-muscle cells is implicated in stabilizing cytoskeleton actin filaments. Binds calcium.
• Tissue Specificity: Detected in cardiac tissue and platelets, the form found in cardiac tissue is a higher molecular weight than the form found in platelets. Expressed at higher levels in the platelets of hypertensive patients with cardiac hypertrophy than in the platelets of hypertensive patients without cardiac hypertrophy (at protein level).
• KEGG Pathway:
  Cardiac muscle contraction (hsa04260)
  Adrenergic sig.ling in cardiomyocytes (hsa04261)
  Motor proteins (hsa04814)
  Cytoskeleton in muscle cells (hsa04820)
  Hypertrophic cardiomyopathy (hsa05410)
  Dilated cardiomyopathy (hsa05414)
• Reactome Pathway:
  Smooth Muscle Contraction (R-HSA-445355)
  RHOV GTPase cycle (R-HSA-9013424)
  Signaling by ALK fusions and activated point mutants (R-HSA-9725370)
  Striated Muscle Contraction (R-HSA-390522)

Molecular Interaction Atlas (MIA) of This DOT

27 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Asbestosis	DISO5XCZ	Strong	Biomarker	[2]
Chronic idiopathic urticaria	DISZA5CE	Strong	Biomarker	[3]
Colon cancer	DISVC52G	Strong	Biomarker	[4]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[4]
Dengue	DISKH221	Strong	Biomarker	[5]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[6]
Esophageal cancer	DISGB2VN	Strong	Biomarker	[7]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[6]
Invasive ductal breast carcinoma	DIS43J58	Strong	Altered Expression	[8]
Lung cancer	DISCM4YA	Strong	Biomarker	[6]
Lung carcinoma	DISTR26C	Strong	Biomarker	[6]
Neoplasm	DISZKGEW	Strong	Biomarker	[4]
Neoplasm of esophagus	DISOLKAQ	Strong	Biomarker	[7]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Genetic Variation	[9]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[6]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[6]
Precancerous condition	DISV06FL	Strong	Biomarker	[7]
Type-1/2 diabetes	DISIUHAP	Strong	Altered Expression	[10]
Inherited bleeding disorder, platelet-type	DISIUNXT	moderate	Biomarker	[11]
Malignant soft tissue neoplasm	DISTC6NO	moderate	Biomarker	[12]
Sarcoma	DISZDG3U	moderate	Biomarker	[12]
TPM4-related platelet disorder	DIS7PVHV	Moderate	Autosomal dominant	[13]
Autosomal dominant macrothrombocytopenia	DISUTMSW	Supportive	Autosomal dominant	[11]
Acute coronary syndrome	DIS7DYEW	Limited	Biomarker	[14]
Osteoporosis	DISF2JE0	Limited	Biomarker	[15]
Squamous cell carcinoma	DISQVIFL	Limited	Altered Expression	[16]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Afimoxifene	DMFORDT	Phase 2	Tropomyosin alpha-4 chain (TPM4) affects the response to substance of Afimoxifene.	[42]
PEITC	DMOMN31	Phase 2	Tropomyosin alpha-4 chain (TPM4) affects the binding of PEITC.	[43]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Tropomyosin alpha-4 chain (TPM4).	[17]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Tropomyosin alpha-4 chain (TPM4).	[29]

25 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 Tropomyosin alpha-4 chain (TPM4).	[18]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Tropomyosin alpha-4 chain (TPM4).	[19]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Tropomyosin alpha-4 chain (TPM4).	[20]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of Tropomyosin alpha-4 chain (TPM4).	[21]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Tropomyosin alpha-4 chain (TPM4).	[22]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Tropomyosin alpha-4 chain (TPM4).	[23]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Tropomyosin alpha-4 chain (TPM4).	[18]
Ivermectin	DMDBX5F	Approved	Ivermectin affects the expression of Tropomyosin alpha-4 chain (TPM4).	[24]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Tropomyosin alpha-4 chain (TPM4).	[25]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Tropomyosin alpha-4 chain (TPM4).	[26]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Tropomyosin alpha-4 chain (TPM4).	[27]
Decitabine	DMQL8XJ	Approved	Decitabine decreases the expression of Tropomyosin alpha-4 chain (TPM4).	[28]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone affects the expression of Tropomyosin alpha-4 chain (TPM4).	[30]
Ampicillin	DMHWE7P	Approved	Ampicillin increases the expression of Tropomyosin alpha-4 chain (TPM4).	[25]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Tropomyosin alpha-4 chain (TPM4).	[31]
Rigosertib	DMOSTXF	Phase 3	Rigosertib increases the expression of Tropomyosin alpha-4 chain (TPM4).	[32]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Tropomyosin alpha-4 chain (TPM4).	[33]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Tropomyosin alpha-4 chain (TPM4).	[34]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Tropomyosin alpha-4 chain (TPM4).	[35]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Tropomyosin alpha-4 chain (TPM4).	[36]
Geldanamycin	DMS7TC5	Discontinued in Phase 2	Geldanamycin increases the expression of Tropomyosin alpha-4 chain (TPM4).	[37]
Torcetrapib	DMDHYM7	Discontinued in Phase 2	Torcetrapib increases the expression of Tropomyosin alpha-4 chain (TPM4).	[38]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Tropomyosin alpha-4 chain (TPM4).	[39]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Tropomyosin alpha-4 chain (TPM4).	[40]
Paraoxon	DMN4ZKC	Investigative	Paraoxon increases the expression of Tropomyosin alpha-4 chain (TPM4).	[41]

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