Details of Drug Off-Target (DOT)

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

• DOT Name: BAG family molecular chaperone regulator 3 (BAG3)
• Synonyms: BAG-3; Bcl-2-associated athanogene 3; Bcl-2-binding protein Bis; Docking protein CAIR-1
• Gene Name: BAG3
• Related Disease:
  Congestive heart failure
  Dilated cardiomyopathy
  Dilated cardiomyopathy 1HH
  Myofibrillar myopathy
  Myofibrillar myopathy 6
  Neuroblastoma
  Alcohol dependence
  Alzheimer disease
  Anxiety
  Anxiety disorder
  Attention deficit hyperactivity disorder
  Breast cancer
  Breast carcinoma
  Carcinoma
  Cardiovascular disease
  Cervical cancer
  Cervical carcinoma
  Charcot marie tooth disease
  Depression
  Dilated cardiomyopathy 1A
  Epithelial ovarian cancer
  HIV infectious disease
  Mental disorder
  Muscular dystrophy
  Ovarian cancer
  Ovarian neoplasm
  Pancreatic cancer
  Pancreatic ductal carcinoma
  Parkinson disease
  Restrictive cardiomyopathy
  Seasonal affective disorder
  Small lymphocytic lymphoma
  Thyroid cancer
  Triple negative breast cancer
  Adult glioblastoma
  Colorectal carcinoma
  Glioblastoma multiforme
  Neoplasm
  Prostate cancer
  Obsolete familial isolated dilated cardiomyopathy
  Advanced cancer
  Thyroid tumor
  B-cell neoplasm
  Cardiac failure
  Ebola virus infection
  Familial dilated cardiomyopathy
  Matthew-Wood syndrome
  Myocardial infarction
  Pancreatic tumour
  Thyroid gland carcinoma
• UniProt ID: BAG3_HUMAN
• Pfam ID: PF02179 ; PF00397
• Sequence:
  MSAATHSPMMQVASGNGDRDPLPPGWEIKIDPQTGWPFFVDHNSRTTTWNDPRVPSEGPK
  ETPSSANGPSREGSRLPPAREGHPVYPQLRPGYIPIPVLHEGAENRQVHPFHVYPQPGMQ
  RFRTEAAAAAPQRSQSPLRGMPETTQPDKQCGQVAAAAAAQPPASHGPERSQSPAASDCS
  SSSSSASLPSSGRSSLGSHQLPRGYISIPVIHEQNVTRPAAQPSFHQAQKTHYPAQQGEY
  QTHQPVYHKIQGDDWEPRPLRAASPFRSSVQGASSREGSPARSSTPLHSPSPIRVHTVVD
  RPQQPMTHRETAPVSQPENKPESKPGPVGPELPPGHIPIQVIRKEVDSKPVSQKPPPPSE
  KVEVKVPPAPVPCPPPSPGPSAVPSSPKSVATEERAAPSTAPAEATPPKPGEAEAPPKHP
  GVLKVEAILEKVQGLEQAVDNFEGKKTDKKYLMIEEYLTKELLALDSVDPEGRADVRQAR
  RDGVRKVQTILEKLEQKAIDVPGQVQVYELQPSNLEADQPLQAIMEMGAVAADKGKKNAG
  NAEDPHTETQQPEATAAATSNPSSMTDTPGNPAAP
• Function: Co-chaperone for HSP70 and HSC70 chaperone proteins. Acts as a nucleotide-exchange factor (NEF) promoting the release of ADP from the HSP70 and HSC70 proteins thereby triggering client/substrate protein release. Nucleotide release is mediated via its binding to the nucleotide-binding domain (NBD) of HSPA8/HSC70 where as the substrate release is mediated via its binding to the substrate-binding domain (SBD) of HSPA8/HSC70. Has anti-apoptotic activity. Plays a role in the HSF1 nucleocytoplasmic transport.
• Reactome Pathway: Regulation of HSF1-mediated heat shock response (R-HSA-3371453)

Molecular Interaction Atlas (MIA) of This DOT

50 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Congestive heart failure	DIS32MEA	Definitive	Biomarker	[1]
Dilated cardiomyopathy	DISX608J	Definitive	Autosomal dominant	[2]
Dilated cardiomyopathy 1HH	DISDBVQP	Definitive	Autosomal dominant	[3]
Myofibrillar myopathy	DISF24LW	Definitive	Autosomal dominant	[2]
Myofibrillar myopathy 6	DIS6BS3B	Definitive	Autosomal dominant	[4]
Neuroblastoma	DISVZBI4	Definitive	Biomarker	[5]
Alcohol dependence	DIS4ZSCO	Strong	Biomarker	[6]
Alzheimer disease	DISF8S70	Strong	Biomarker	[7]
Anxiety	DISIJDBA	Strong	Biomarker	[8]
Anxiety disorder	DISBI2BT	Strong	Biomarker	[8]
Attention deficit hyperactivity disorder	DISL8MX9	Strong	Genetic Variation	[9]
Breast cancer	DIS7DPX1	Strong	Biomarker	[10]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[10]
Carcinoma	DISH9F1N	Strong	Altered Expression	[11]
Cardiovascular disease	DIS2IQDX	Strong	Biomarker	[12]
Cervical cancer	DISFSHPF	Strong	Biomarker	[13]
Cervical carcinoma	DIST4S00	Strong	Biomarker	[13]
Charcot marie tooth disease	DIS3BT2L	Strong	Genetic Variation	[14]
Depression	DIS3XJ69	Strong	Altered Expression	[15]
Dilated cardiomyopathy 1A	DIS0RK9Z	Strong	Biomarker	[16]
Epithelial ovarian cancer	DIS56MH2	Strong	Altered Expression	[17]
HIV infectious disease	DISO97HC	Strong	Biomarker	[18]
Mental disorder	DIS3J5R8	Strong	Biomarker	[19]
Muscular dystrophy	DISJD6P7	Strong	Biomarker	[20]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[21]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[21]
Pancreatic cancer	DISJC981	Strong	Biomarker	[22]
Pancreatic ductal carcinoma	DIS26F9Q	Strong	Altered Expression	[23]
Parkinson disease	DISQVHKL	Strong	Biomarker	[24]
Restrictive cardiomyopathy	DISFAF31	Strong	Genetic Variation	[25]
Seasonal affective disorder	DIS908VO	Strong	Altered Expression	[26]
Small lymphocytic lymphoma	DIS30POX	Strong	Altered Expression	[27]
Thyroid cancer	DIS3VLDH	Strong	Altered Expression	[28]
Triple negative breast cancer	DISAMG6N	Strong	Biomarker	[29]
Adult glioblastoma	DISVP4LU	moderate	Altered Expression	[30]
Colorectal carcinoma	DIS5PYL0	moderate	Biomarker	[31]
Glioblastoma multiforme	DISK8246	moderate	Altered Expression	[30]
Neoplasm	DISZKGEW	moderate	Biomarker	[29]
Prostate cancer	DISF190Y	moderate	Altered Expression	[32]
Obsolete familial isolated dilated cardiomyopathy	DIS4FXO4	Supportive	Autosomal dominant	[33]
Advanced cancer	DISAT1Z9	Disputed	Genetic Variation	[23]
Thyroid tumor	DISLVKMD	Disputed	Altered Expression	[28]
B-cell neoplasm	DISVY326	Limited	Biomarker	[34]
Cardiac failure	DISDC067	Limited	Biomarker	[1]
Ebola virus infection	DISJAVM1	Limited	Biomarker	[35]
Familial dilated cardiomyopathy	DISBHDU9	Limited	Biomarker	[16]
Matthew-Wood syndrome	DISA7HR7	Limited	Biomarker	[36]
Myocardial infarction	DIS655KI	Limited	Biomarker	[37]
Pancreatic tumour	DIS3U0LK	Limited	Biomarker	[22]
Thyroid gland carcinoma	DISMNGZ0	Limited	Altered Expression	[38]

This DOT Affected the Drug Response of 3 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Fluorouracil	DMUM7HZ	Approved	BAG family molecular chaperone regulator 3 (BAG3) affects the response to substance of Fluorouracil.	[72]
ABT-737	DML0DBV	Terminated	BAG family molecular chaperone regulator 3 (BAG3) decreases the response to substance of ABT-737.	[32]
Staurosporine	DM0E9BR	Investigative	BAG family molecular chaperone regulator 3 (BAG3) decreases the response to substance of Staurosporine.	[74]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of BAG family molecular chaperone regulator 3 (BAG3).	[39]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of BAG family molecular chaperone regulator 3 (BAG3).	[40]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of BAG family molecular chaperone regulator 3 (BAG3).	[41]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of BAG family molecular chaperone regulator 3 (BAG3).	[42]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of BAG family molecular chaperone regulator 3 (BAG3).	[43]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of BAG family molecular chaperone regulator 3 (BAG3).	[44]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of BAG family molecular chaperone regulator 3 (BAG3).	[45]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of BAG family molecular chaperone regulator 3 (BAG3).	[46]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of BAG family molecular chaperone regulator 3 (BAG3).	[47]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide affects the expression of BAG family molecular chaperone regulator 3 (BAG3).	[48]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of BAG family molecular chaperone regulator 3 (BAG3).	[49]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of BAG family molecular chaperone regulator 3 (BAG3).	[44]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of BAG family molecular chaperone regulator 3 (BAG3).	[50]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of BAG family molecular chaperone regulator 3 (BAG3).	[51]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of BAG family molecular chaperone regulator 3 (BAG3).	[52]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of BAG family molecular chaperone regulator 3 (BAG3).	[53]
Menthol	DMG2KW7	Approved	Menthol increases the expression of BAG family molecular chaperone regulator 3 (BAG3).	[54]
Capsaicin	DMGMF6V	Approved	Capsaicin increases the expression of BAG family molecular chaperone regulator 3 (BAG3).	[55]
Acetic Acid, Glacial	DM4SJ5Y	Approved	Acetic Acid, Glacial increases the expression of BAG family molecular chaperone regulator 3 (BAG3).	[56]
Motexafin gadolinium	DMEJKRF	Approved	Motexafin gadolinium increases the expression of BAG family molecular chaperone regulator 3 (BAG3).	[56]
Beta-carotene	DM0RXBT	Approved	Beta-carotene decreases the expression of BAG family molecular chaperone regulator 3 (BAG3).	[57]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of BAG family molecular chaperone regulator 3 (BAG3).	[58]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of BAG family molecular chaperone regulator 3 (BAG3).	[59]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of BAG family molecular chaperone regulator 3 (BAG3).	[40]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of BAG family molecular chaperone regulator 3 (BAG3).	[60]
Celastrol	DMWQIJX	Preclinical	Celastrol increases the expression of BAG family molecular chaperone regulator 3 (BAG3).	[62]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of BAG family molecular chaperone regulator 3 (BAG3).	[63]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of BAG family molecular chaperone regulator 3 (BAG3).	[64]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of BAG family molecular chaperone regulator 3 (BAG3).	[65]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of BAG family molecular chaperone regulator 3 (BAG3).	[66]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of BAG family molecular chaperone regulator 3 (BAG3).	[67]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of BAG family molecular chaperone regulator 3 (BAG3).	[68]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate decreases the expression of BAG family molecular chaperone regulator 3 (BAG3).	[69]
crotylaldehyde	DMTWRQI	Investigative	crotylaldehyde increases the expression of BAG family molecular chaperone regulator 3 (BAG3).	[70]
Tributylstannanyl	DMHN7CB	Investigative	Tributylstannanyl affects the expression of BAG family molecular chaperone regulator 3 (BAG3).	[71]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of BAG family molecular chaperone regulator 3 (BAG3).	[61]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of BAG family molecular chaperone regulator 3 (BAG3).	[61]

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