Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNJKJ6Q)

• DOT Name: Caldesmon (CALD1)
• Synonyms: CDM
• Gene Name: CALD1
• Related Disease:
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Adult teratoma
  Autosomal dominant polycystic kidney disease
  Bladder cancer
  Breast cancer
  Breast carcinoma
  Carcinoma of liver and intrahepatic biliary tract
  Depression
  Diabetic kidney disease
  Endometriosis
  Glioma
  Hepatitis B virus infection
  Hepatocellular carcinoma
  High blood pressure
  Huntington disease
  Juvenile idiopathic arthritis
  Leiomyoma
  Limb-girdle muscular dystrophy
  Liver cancer
  Malignant soft tissue neoplasm
  Metastatic malignant neoplasm
  Myopathy
  Nephropathy
  Obesity
  Oral cavity squamous cell carcinoma
  Parkinson disease
  Polymyositis
  Polyp
  Sarcoma
  Stroke
  Teratoma
  Type-1 diabetes
  Uterine fibroids
  Acute myelogenous leukaemia
  Adenovirus infection
  Gastric cancer
  Gastrointestinal stromal tumour
  Hypoglycemia
  Lateral meningocele syndrome
  Leiomyosarcoma
  Limb-mammary syndrome
  Stomach cancer
  Fetal growth restriction
  Prostate cancer
  Rheumatoid arthritis
• UniProt ID: CALD1_HUMAN
• Pfam ID: PF02029
• Sequence:
  MDDFERRRELRRQKREEMRLEAERIAYQRNDDDEEEAARERRRRARQERLRQKQEEESLG
  QVTDQVEVNAQNSVPDEEAKTTTTNTQVEGDDEAAFLERLARREERRQKRLQEALERQKE
  FDPTITDASLSLPSRRMQNDTAENETTEKEEKSESRQERYEIEETETVTKSYQKNDWRDA
  EENKKEDKEKEEEEEEKPKRGSIGENQVEVMVEEKTTESQEETVVMSLKNGQISSEEPKQ
  EEEREQGSDEISHHEKMEEEDKERAEAERARLEAEERERIKAEQDKKIADERARIEAEEK
  AAAQERERREAEERERMREEEKRAAEERQRIKEEEKRAAEERQRIKEEEKRAAEERQRIK
  EEEKRAAEERQRARAEEEEKAKVEEQKRNKQLEEKKHAMQETKIKGEKVEQKIEGKWVNE
  KKAQEDKLQTAVLKKQGEEKGTKVQAKREKLQEDKPTFKKEEIKDEKIKKDKEPKEEVKS
  FMDRKKGFTEVKSQNGEFMTHKLKHTENTFSRPGGRASVDTKEAEGAPQVEAGKRLEELR
  RRRGETESEEFEKLKQKQQEAALELEELKKKREERRKVLEEEEQRRKQEEADRKLREEEE
  KRRLKEEIERRRAEAAEKRQKMPEDGLSDDKKPFKCFTPKGSSLKIEERAEFLNKSVQKS
  SGVKSTHQAAIVSKIDSRLEQYTSAIEGTKSAKPTKPAASDLPVPAEGVRNIKSMWEKGN
  VFSSPTAAGTPNKETAGLKVGVSSRINEWLTKTPDGNKSPAPKPSDLRPGDVSSKRNLWE
  KQSVDKVTSPTKV
• Function: Actin- and myosin-binding protein implicated in the regulation of actomyosin interactions in smooth muscle and nonmuscle cells (could act as a bridge between myosin and actin filaments). Stimulates actin binding of tropomyosin which increases the stabilization of actin filament structure. In muscle tissues, inhibits the actomyosin ATPase by binding to F-actin. This inhibition is attenuated by calcium-calmodulin and is potentiated by tropomyosin. Interacts with actin, myosin, two molecules of tropomyosin and with calmodulin. Also plays an essential role during cellular mitosis and receptor capping. Involved in Schwann cell migration during peripheral nerve regeneration.
• Tissue Specificity: High-molecular-weight caldesmon (isoform 1) is predominantly expressed in smooth muscles, whereas low-molecular-weight caldesmon (isoforms 2, 3, 4 and 5) are widely distributed in non-muscle tissues and cells. Not expressed in skeletal muscle or heart.
• KEGG Pathway: Vascular smooth muscle contraction (hsa04270)
• Reactome Pathway: Smooth Muscle Contraction (R-HSA-445355)

Molecular Interaction Atlas (MIA) of This DOT

47 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colon cancer	DISVC52G	Definitive	Altered Expression	[1]
Colon carcinoma	DISJYKUO	Definitive	Altered Expression	[1]
Colorectal carcinoma	DIS5PYL0	Definitive	Altered Expression	[1]
Adult teratoma	DISBY81U	Strong	Biomarker	[2]
Autosomal dominant polycystic kidney disease	DISBHWUI	Strong	Altered Expression	[3]
Bladder cancer	DISUHNM0	Strong	Altered Expression	[4]
Breast cancer	DIS7DPX1	Strong	Biomarker	[5]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[5]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Strong	Biomarker	[6]
Depression	DIS3XJ69	Strong	Genetic Variation	[7]
Diabetic kidney disease	DISJMWEY	Strong	Genetic Variation	[8]
Endometriosis	DISX1AG8	Strong	Altered Expression	[9]
Glioma	DIS5RPEH	Strong	Altered Expression	[10]
Hepatitis B virus infection	DISLQ2XY	Strong	Biomarker	[11]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[12]
High blood pressure	DISY2OHH	Strong	Genetic Variation	[7]
Huntington disease	DISQPLA4	Strong	Genetic Variation	[13]
Juvenile idiopathic arthritis	DISQZGBV	Strong	Biomarker	[14]
Leiomyoma	DISLDDFN	Strong	Biomarker	[15]
Limb-girdle muscular dystrophy	DISI9Y1Z	Strong	Genetic Variation	[16]
Liver cancer	DISDE4BI	Strong	Biomarker	[6]
Malignant soft tissue neoplasm	DISTC6NO	Strong	Biomarker	[17]
Metastatic malignant neoplasm	DIS86UK6	Strong	Altered Expression	[18]
Myopathy	DISOWG27	Strong	Biomarker	[16]
Nephropathy	DISXWP4P	Strong	Biomarker	[19]
Obesity	DIS47Y1K	Strong	Genetic Variation	[20]
Oral cavity squamous cell carcinoma	DISQVJVA	Strong	Altered Expression	[18]
Parkinson disease	DISQVHKL	Strong	Biomarker	[21]
Polymyositis	DIS5DHFP	Strong	Biomarker	[11]
Polyp	DISRSLYF	Strong	Biomarker	[22]
Sarcoma	DISZDG3U	Strong	Biomarker	[17]
Stroke	DISX6UHX	Strong	Genetic Variation	[20]
Teratoma	DIS6ICY4	Strong	Biomarker	[2]
Type-1 diabetes	DIS7HLUB	Strong	Genetic Variation	[8]
Uterine fibroids	DISBZRMJ	Strong	Biomarker	[23]
Acute myelogenous leukaemia	DISCSPTN	moderate	Genetic Variation	[24]
Adenovirus infection	DISUYSBZ	moderate	Biomarker	[25]
Gastric cancer	DISXGOUK	moderate	Biomarker	[26]
Gastrointestinal stromal tumour	DIS6TJYS	moderate	Biomarker	[27]
Hypoglycemia	DISRCKR7	moderate	Biomarker	[28]
Lateral meningocele syndrome	DISG74RP	moderate	Biomarker	[29]
Leiomyosarcoma	DIS6COXM	moderate	Biomarker	[30]
Limb-mammary syndrome	DIS7H4FP	moderate	Biomarker	[29]
Stomach cancer	DISKIJSX	moderate	Biomarker	[26]
Fetal growth restriction	DIS5WEJ5	Limited	Altered Expression	[31]
Prostate cancer	DISF190Y	Limited	Posttranslational Modification	[32]
Rheumatoid arthritis	DISTSB4J	Limited	Biomarker	[33]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Caldesmon (CALD1) affects the response to substance of Doxorubicin.	[59]
NAPQI	DM8F5LR	Investigative	Caldesmon (CALD1) affects the response to substance of NAPQI.	[60]

5 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 Caldesmon (CALD1).	[34]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Caldesmon (CALD1).	[38]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Caldesmon (CALD1).	[48]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of Caldesmon (CALD1).	[50]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Caldesmon (CALD1).	[57]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Caldesmon (CALD1).	[35]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Caldesmon (CALD1).	[36]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Caldesmon (CALD1).	[37]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Caldesmon (CALD1).	[39]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Caldesmon (CALD1).	[40]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Caldesmon (CALD1).	[41]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Caldesmon (CALD1).	[42]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Caldesmon (CALD1).	[43]
Isotretinoin	DM4QTBN	Approved	Isotretinoin increases the expression of Caldesmon (CALD1).	[44]
Azacitidine	DMTA5OE	Approved	Azacitidine increases the expression of Caldesmon (CALD1).	[45]
Simvastatin	DM30SGU	Approved	Simvastatin decreases the expression of Caldesmon (CALD1).	[46]
Benzatropine	DMF7EXL	Approved	Benzatropine decreases the expression of Caldesmon (CALD1).	[47]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Caldesmon (CALD1).	[42]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Caldesmon (CALD1).	[49]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Caldesmon (CALD1).	[51]
Geldanamycin	DMS7TC5	Discontinued in Phase 2	Geldanamycin increases the expression of Caldesmon (CALD1).	[52]
Torcetrapib	DMDHYM7	Discontinued in Phase 2	Torcetrapib increases the expression of Caldesmon (CALD1).	[53]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Caldesmon (CALD1).	[54]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Caldesmon (CALD1).	[55]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Caldesmon (CALD1).	[56]
Rapamycin Immunosuppressant Drug	DM678IB	Investigative	Rapamycin Immunosuppressant Drug increases the expression of Caldesmon (CALD1).	[58]

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