Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTW2O4GD)

• DOT Name: GTP-binding protein RAD (RRAD)
• Synonyms: RAD1; Ras associated with diabetes
• Gene Name: RRAD
• Related Disease:
  Chondrosarcoma
  Glioblastoma multiforme
  Melanoma
  Adult glioblastoma
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Carcinoma of esophagus
  Cardiac disease
  Cardiac failure
  Chagas disease
  Chromosomal disorder
  Congestive heart failure
  Coronary heart disease
  Esophageal adenocarcinoma
  Esophageal cancer
  Esophageal squamous cell carcinoma
  Familial multiple trichoepithelioma
  Lung adenocarcinoma
  Lung cancer
  Lung carcinoma
  Nasopharyngeal carcinoma
  Neoplasm
  Neoplasm of esophagus
  Non-small-cell lung cancer
  Stroke
  Amyotrophic lateral sclerosis
  Carcinoma
  Brugada syndrome
  Hepatocellular carcinoma
  High blood pressure
  Motor neurone disease
  Prostate cancer
  Prostate carcinoma
• UniProt ID: RAD_HUMAN
• PDB ID: 2DPX; 2GJS; 3Q72; 3Q7P; 3Q7Q
• Pfam ID: PF00071
• Sequence:
  MTLNGGGSGAGGSRGGGQERERRRGSTPWGPAPPLHRRSMPVDERDLQAALTPGALTAAA
  AGTGTQGPRLDWPEDSEDSLSSGGSDSDESVYKVLLLGAPGVGKSALARIFGGVEDGPEA
  EAAGHTYDRSIVVDGEEASLMVYDIWEQDGGRWLPGHCMAMGDAYVIVYSVTDKGSFEKA
  SELRVQLRRARQTDDVPIILVGNKSDLVRSREVSVDEGRACAVVFDCKFIETSAALHHNV
  QALFEGVVRQIRLRRDSKEANARRQAGTRRRESLGKKAKRFLGRIVARNSRKMAFRAKSK
  SCHDLSVL
• Function: May regulate basal voltage-dependent L-type Ca(2+) currents and be required for beta-adrenergic augmentation of Ca(2+) influx in cardiomyocytes, thereby regulating increases in heart rate and contractile force. May play an important role in cardiac antiarrhythmia via the strong suppression of voltage-gated L-type Ca(2+) currents. Regulates voltage-dependent L-type calcium channel subunit alpha-1C trafficking to the cell membrane. Inhibits cardiac hypertrophy through the calmodulin-dependent kinase II (CaMKII) pathway. Inhibits phosphorylation and activation of CAMK2D.
• Tissue Specificity: Most abundantly expressed in the heart. Also found in the skeletal muscle and lung. Lesser amounts in placenta and kidney. Also detected in adipose tissue. Overexpressed in muscle of type II diabetic humans.
• Reactome Pathway: NGF-stimulated transcription (R-HSA-9031628)

Molecular Interaction Atlas (MIA) of This DOT

35 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Chondrosarcoma	DIS4I7JB	Definitive	Altered Expression	[1]
Glioblastoma multiforme	DISK8246	Definitive	Biomarker	[2]
Melanoma	DIS1RRCY	Definitive	Biomarker	[3]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[4]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[5]
Breast cancer	DIS7DPX1	Strong	Biomarker	[6]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[6]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[7]
Carcinoma of esophagus	DISS6G4D	Strong	Posttranslational Modification	[8]
Cardiac disease	DISVO1I5	Strong	Biomarker	[9]
Cardiac failure	DISDC067	Strong	Altered Expression	[10]
Chagas disease	DIS8KNVF	Strong	Biomarker	[11]
Chromosomal disorder	DISM5BB5	Strong	Biomarker	[12]
Congestive heart failure	DIS32MEA	Strong	Altered Expression	[10]
Coronary heart disease	DIS5OIP1	Strong	Genetic Variation	[13]
Esophageal adenocarcinoma	DISODWFP	Strong	Posttranslational Modification	[8]
Esophageal cancer	DISGB2VN	Strong	Posttranslational Modification	[8]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Posttranslational Modification	[8]
Familial multiple trichoepithelioma	DISKZAUY	Strong	Posttranslational Modification	[8]
Lung adenocarcinoma	DISD51WR	Strong	Posttranslational Modification	[7]
Lung cancer	DISCM4YA	Strong	Altered Expression	[14]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[14]
Nasopharyngeal carcinoma	DISAOTQ0	Strong	Biomarker	[15]
Neoplasm	DISZKGEW	Strong	Altered Expression	[5]
Neoplasm of esophagus	DISOLKAQ	Strong	Posttranslational Modification	[8]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[16]
Stroke	DISX6UHX	Strong	Biomarker	[17]
Amyotrophic lateral sclerosis	DISF7HVM	moderate	Biomarker	[18]
Carcinoma	DISH9F1N	moderate	Genetic Variation	[19]
Brugada syndrome	DISSGN0E	Limited	Autosomal dominant	[20]
Hepatocellular carcinoma	DIS0J828	Limited	Altered Expression	[5]
High blood pressure	DISY2OHH	Limited	Genetic Variation	[21]
Motor neurone disease	DISUHWUI	Limited	Biomarker	[18]
Prostate cancer	DISF190Y	Limited	Biomarker	[22]
Prostate carcinoma	DISMJPLE	Limited	Biomarker	[22]

28 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 GTP-binding protein RAD (RRAD).	[23]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of GTP-binding protein RAD (RRAD).	[24]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of GTP-binding protein RAD (RRAD).	[25]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of GTP-binding protein RAD (RRAD).	[26]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of GTP-binding protein RAD (RRAD).	[27]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of GTP-binding protein RAD (RRAD).	[23]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of GTP-binding protein RAD (RRAD).	[28]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of GTP-binding protein RAD (RRAD).	[29]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of GTP-binding protein RAD (RRAD).	[30]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of GTP-binding protein RAD (RRAD).	[31]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of GTP-binding protein RAD (RRAD).	[7]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of GTP-binding protein RAD (RRAD).	[33]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of GTP-binding protein RAD (RRAD).	[34]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of GTP-binding protein RAD (RRAD).	[35]
Ethanol	DMDRQZU	Approved	Ethanol decreases the expression of GTP-binding protein RAD (RRAD).	[36]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of GTP-binding protein RAD (RRAD).	[37]
Malathion	DMXZ84M	Approved	Malathion increases the expression of GTP-binding protein RAD (RRAD).	[38]
Amphotericin B	DMTAJQE	Approved	Amphotericin B decreases the expression of GTP-binding protein RAD (RRAD).	[39]
Melphalan	DMOLNHF	Approved	Melphalan increases the expression of GTP-binding protein RAD (RRAD).	[40]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of GTP-binding protein RAD (RRAD).	[41]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of GTP-binding protein RAD (RRAD).	[42]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of GTP-binding protein RAD (RRAD).	[43]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of GTP-binding protein RAD (RRAD).	[45]
PIRINIXIC ACID	DM82Y75	Preclinical	PIRINIXIC ACID increases the expression of GTP-binding protein RAD (RRAD).	[46]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of GTP-binding protein RAD (RRAD).	[47]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of GTP-binding protein RAD (RRAD).	[48]
Paraquat	DMR8O3X	Investigative	Paraquat increases the expression of GTP-binding protein RAD (RRAD).	[49]
Lithium chloride	DMHYLQ2	Investigative	Lithium chloride increases the expression of GTP-binding protein RAD (RRAD).	[50]

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 GTP-binding protein RAD (RRAD).	[44]

References

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