Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTD73X6R)

• DOT Name: Tropomyosin alpha-1 chain (TPM1)
• Synonyms: Alpha-tropomyosin; Tropomyosin-1
• Gene Name: TPM1
• Related Disease:
  Benign prostatic hyperplasia
  Familial dilated cardiomyopathy
  Hypertrophic cardiomyopathy
  Hypertrophic cardiomyopathy 3
  Neoplasm
  Alzheimer disease
  Arrhythmia
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Carcinoma
  Carcinoma of esophagus
  Cardiac disease
  Cardiac failure
  Cholangiocarcinoma
  Clear cell renal carcinoma
  Congestive heart failure
  Dilated cardiomyopathy 1A
  Dilated cardiomyopathy 1Y
  Ebstein anomaly
  Esophageal squamous cell carcinoma
  Familial hypertrophic cardiomyopathy
  Glioma
  High blood pressure
  Hypercholesterolemia, familial, 1
  Keloid
  Melanoma
  Non-insulin dependent diabetes
  Polycystic ovarian syndrome
  Psoriasis
  Renal cell carcinoma
  Cervical carcinoma
  Dilated cardiomyopathy
  Metastatic malignant neoplasm
  Left ventricular noncompaction
  Obsolete familial isolated dilated cardiomyopathy
  Advanced cancer
  Bone osteosarcoma
  Cardiomyopathy
  Colorectal carcinoma
  Esophageal cancer
  Myopathy
  Neoplasm of esophagus
  Osteoarthritis
  Osteosarcoma
  Parkinson disease
  Squamous cell carcinoma
  Tetralogy of fallot
  Arrhythmogenic right ventricular cardiomyopathy
• UniProt ID: TPM1_HUMAN
• PDB ID: 3MUD; 5KHT; 6UT2; 6X5Z; 7UTI; 7UTL; 8EFH; 8EFI; 8ENC
• Pfam ID: PF00261
• Sequence:
  MDAIKKKMQMLKLDKENALDRAEQAEADKKAAEDRSKQLEDELVSLQKKLKGTEDELDKY
  SEALKDAQEKLELAEKKATDAEADVASLNRRIQLVEEELDRAQERLATALQKLEEAEKAA
  DESERGMKVIESRAQKDEEKMEIQEIQLKEAKHIAEDADRKYEEVARKLVIIESDLERAE
  ERAELSEGKCAELEEELKTVTNNLKSLEAQAEKYSQKEDRYEEEIKVLSDKLKEAETRAE
  FAERSVTKLEKSIDDLEDELYAQKLKYKAISEELDHALNDMTSI
• 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.
• Tissue Specificity: Detected in primary breast cancer tissues but undetectable in normal breast tissues in Sudanese patients. Isoform 1 is expressed in adult and fetal skeletal muscle and cardiac tissues, with higher expression levels in the cardiac tissues. Isoform 10 is expressed in adult and fetal cardiac tissues, but not in skeletal muscle.
• KEGG Pathway:
  Cardiac muscle contraction (hsa04260)
  Adrenergic sig.ling in cardiomyocytes (hsa04261)
  Motor proteins (hsa04814)
  Cytoskeleton in muscle cells (hsa04820)
  MicroR.s in cancer (hsa05206)
  Hypertrophic cardiomyopathy (hsa05410)
  Dilated cardiomyopathy (hsa05414)
• Reactome Pathway:
  Smooth Muscle Contraction (R-HSA-445355)
  Striated Muscle Contraction (R-HSA-390522)

Molecular Interaction Atlas (MIA) of This DOT

49 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Benign prostatic hyperplasia	DISI3CW2	Definitive	Altered Expression	[1]
Familial dilated cardiomyopathy	DISBHDU9	Definitive	Genetic Variation	[2]
Hypertrophic cardiomyopathy	DISQG2AI	Definitive	Autosomal dominant	[3]
Hypertrophic cardiomyopathy 3	DISBVV0E	Definitive	Autosomal dominant	[4]
Neoplasm	DISZKGEW	Definitive	Altered Expression	[5]
Alzheimer disease	DISF8S70	Strong	Biomarker	[6]
Arrhythmia	DISFF2NI	Strong	Genetic Variation	[7]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[8]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[8]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[9]
Carcinoma	DISH9F1N	Strong	Altered Expression	[10]
Carcinoma of esophagus	DISS6G4D	Strong	Altered Expression	[11]
Cardiac disease	DISVO1I5	Strong	Biomarker	[12]
Cardiac failure	DISDC067	Strong	Genetic Variation	[12]
Cholangiocarcinoma	DIS71F6X	Strong	Biomarker	[13]
Clear cell renal carcinoma	DISBXRFJ	Strong	Altered Expression	[5]
Congestive heart failure	DIS32MEA	Strong	Genetic Variation	[12]
Dilated cardiomyopathy 1A	DIS0RK9Z	Strong	Genetic Variation	[14]
Dilated cardiomyopathy 1Y	DISX0ETB	Strong	Autosomal dominant	[15]
Ebstein anomaly	DISO3NHV	Strong	Genetic Variation	[16]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Altered Expression	[17]
Familial hypertrophic cardiomyopathy	DISQ89HN	Strong	CausalMutation	[18]
Glioma	DIS5RPEH	Strong	Altered Expression	[19]
High blood pressure	DISY2OHH	Strong	Biomarker	[20]
Hypercholesterolemia, familial, 1	DISU411W	Strong	Genetic Variation	[21]
Keloid	DISV09JY	Strong	Biomarker	[22]
Melanoma	DIS1RRCY	Strong	Biomarker	[23]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Altered Expression	[24]
Polycystic ovarian syndrome	DISZ2BNG	Strong	Biomarker	[25]
Psoriasis	DIS59VMN	Strong	Posttranslational Modification	[26]
Renal cell carcinoma	DISQZ2X8	Strong	Altered Expression	[5]
Cervical carcinoma	DIST4S00	moderate	Biomarker	[27]
Dilated cardiomyopathy	DISX608J	Moderate	Autosomal dominant	[3]
Metastatic malignant neoplasm	DIS86UK6	moderate	Altered Expression	[5]
Left ventricular noncompaction	DISJ4QEG	Supportive	Autosomal dominant	[28]
Obsolete familial isolated dilated cardiomyopathy	DIS4FXO4	Supportive	Autosomal dominant	[29]
Advanced cancer	DISAT1Z9	Disputed	Altered Expression	[5]
Bone osteosarcoma	DIST1004	Limited	Altered Expression	[30]
Cardiomyopathy	DISUPZRG	Limited	Genetic Variation	[31]
Colorectal carcinoma	DIS5PYL0	Limited	Genetic Variation	[32]
Esophageal cancer	DISGB2VN	Limited	Altered Expression	[11]
Myopathy	DISOWG27	Limited	Genetic Variation	[33]
Neoplasm of esophagus	DISOLKAQ	Limited	Altered Expression	[11]
Osteoarthritis	DIS05URM	Limited	Altered Expression	[34]
Osteosarcoma	DISLQ7E2	Limited	Altered Expression	[30]
Parkinson disease	DISQVHKL	Limited	Genetic Variation	[35]
Squamous cell carcinoma	DISQVIFL	Limited	Altered Expression	[36]
Tetralogy of fallot	DISMHFNW	Limited	Genetic Variation	[37]
Arrhythmogenic right ventricular cardiomyopathy	DIS3V2BE	No Known	Autosomal dominant	[3]

This DOT Affected the Drug Response of 6 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Fluorouracil	DMUM7HZ	Approved	Tropomyosin alpha-1 chain (TPM1) affects the response to substance of Fluorouracil.	[67]
Topotecan	DMP6G8T	Approved	Tropomyosin alpha-1 chain (TPM1) affects the response to substance of Topotecan.	[67]
Mitoxantrone	DMM39BF	Approved	Tropomyosin alpha-1 chain (TPM1) affects the response to substance of Mitoxantrone.	[67]
Cyclophosphamide	DM4O2Z7	Approved	Tropomyosin alpha-1 chain (TPM1) affects the response to substance of Cyclophosphamide.	[67]
PEITC	DMOMN31	Phase 2	Tropomyosin alpha-1 chain (TPM1) affects the binding of PEITC.	[68]
Sulforaphane	DMQY3L0	Investigative	Tropomyosin alpha-1 chain (TPM1) affects the binding of Sulforaphane.	[68]

28 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 Tropomyosin alpha-1 chain (TPM1).	[38]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Tropomyosin alpha-1 chain (TPM1).	[39]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Tropomyosin alpha-1 chain (TPM1).	[40]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Tropomyosin alpha-1 chain (TPM1).	[41]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Tropomyosin alpha-1 chain (TPM1).	[42]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Tropomyosin alpha-1 chain (TPM1).	[43]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Tropomyosin alpha-1 chain (TPM1).	[44]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Tropomyosin alpha-1 chain (TPM1).	[46]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Tropomyosin alpha-1 chain (TPM1).	[47]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Tropomyosin alpha-1 chain (TPM1).	[48]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Tropomyosin alpha-1 chain (TPM1).	[49]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Tropomyosin alpha-1 chain (TPM1).	[50]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Tropomyosin alpha-1 chain (TPM1).	[51]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Tropomyosin alpha-1 chain (TPM1).	[52]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of Tropomyosin alpha-1 chain (TPM1).	[53]
Ethinyl estradiol	DMODJ40	Approved	Ethinyl estradiol decreases the expression of Tropomyosin alpha-1 chain (TPM1).	[54]
Etretinate	DM2CZFA	Approved	Etretinate decreases the expression of Tropomyosin alpha-1 chain (TPM1).	[56]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Tropomyosin alpha-1 chain (TPM1).	[57]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Tropomyosin alpha-1 chain (TPM1).	[58]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Tropomyosin alpha-1 chain (TPM1).	[59]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Tropomyosin alpha-1 chain (TPM1).	[61]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Tropomyosin alpha-1 chain (TPM1).	[62]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Tropomyosin alpha-1 chain (TPM1).	[52]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Tropomyosin alpha-1 chain (TPM1).	[58]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Tropomyosin alpha-1 chain (TPM1).	[63]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Tropomyosin alpha-1 chain (TPM1).	[64]
Lithium chloride	DMHYLQ2	Investigative	Lithium chloride increases the expression of Tropomyosin alpha-1 chain (TPM1).	[65]
CH-223191	DMMJZYC	Investigative	CH-223191 increases the expression of Tropomyosin alpha-1 chain (TPM1).	[66]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic increases the ubiquitination of Tropomyosin alpha-1 chain (TPM1).	[45]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Tropomyosin alpha-1 chain (TPM1).	[60]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Dihydroartemisinin	DMBXVMZ	Approved	Dihydroartemisinin affects the binding of Tropomyosin alpha-1 chain (TPM1).	[55]

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