Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBSJGN3)

• DOT Name: Signal transducer and activator of transcription 5A (STAT5A)
• Gene Name: STAT5A
• Related Disease:
  Undifferentiated carcinoma
  Acute lymphocytic leukaemia
  Adenocarcinoma
  Adult glioblastoma
  Adult lymphoma
  Advanced cancer
  B-cell neoplasm
  Breast lobular carcinoma
  Breast neoplasm
  Childhood acute lymphoblastic leukemia
  Classic Hodgkin lymphoma
  Colorectal carcinoma
  Ductal breast carcinoma in situ
  Hepatitis C virus infection
  Hepatocellular carcinoma
  Lung carcinoma
  Lung neoplasm
  Lymphoma
  Metastatic malignant neoplasm
  Myocardial ischemia
  Non-insulin dependent diabetes
  Non-small-cell lung cancer
  Pediatric lymphoma
  Polycythemia vera
  Precancerous condition
  Prostate cancer
  Prostate carcinoma
  Small lymphocytic lymphoma
  Squamous cell carcinoma
  Systemic lupus erythematosus
  T-cell acute lymphoblastic leukaemia
  Type-1 diabetes
  Chronic kidney disease
  Colon cancer
  Colon carcinoma
  Carcinoma
  leukaemia
  Leukemia
  Lung cancer
  Mastocytosis
  Myeloproliferative neoplasm
  Neoplasm
  Prostate neoplasm
  Systemic mastocytosis
• UniProt ID: STA5A_HUMAN
• PDB ID: 7TVA; 7TVB; 7UBT; 7UC6; 7UC7
• Pfam ID: PF00017 ; PF01017 ; PF02864 ; PF02865 ; PF21354
• Sequence:
  MAGWIQAQQLQGDALRQMQVLYGQHFPIEVRHYLAQWIESQPWDAIDLDNPQDRAQATQL
  LEGLVQELQKKAEHQVGEDGFLLKIKLGHYATQLQKTYDRCPLELVRCIRHILYNEQRLV
  REANNCSSPAGILVDAMSQKHLQINQTFEELRLVTQDTENELKKLQQTQEYFIIQYQESL
  RIQAQFAQLAQLSPQERLSRETALQQKQVSLEAWLQREAQTLQQYRVELAEKHQKTLQLL
  RKQQTIILDDELIQWKRRQQLAGNGGPPEGSLDVLQSWCEKLAEIIWQNRQQIRRAEHLC
  QQLPIPGPVEEMLAEVNATITDIISALVTSTFIIEKQPPQVLKTQTKFAATVRLLVGGKL
  NVHMNPPQVKATIISEQQAKSLLKNENTRNECSGEILNNCCVMEYHQATGTLSAHFRNMS
  LKRIKRADRRGAESVTEEKFTVLFESQFSVGSNELVFQVKTLSLPVVVIVHGSQDHNATA
  TVLWDNAFAEPGRVPFAVPDKVLWPQLCEALNMKFKAEVQSNRGLTKENLVFLAQKLFNN
  SSSHLEDYSGLSVSWSQFNRENLPGWNYTFWQWFDGVMEVLKKHHKPHWNDGAILGFVNK
  QQAHDLLINKPDGTFLLRFSDSEIGGITIAWKFDSPERNLWNLKPFTTRDFSIRSLADRL
  GDLSYLIYVFPDRPKDEVFSKYYTPVLAKAVDGYVKPQIKQVVPEFVNASADAGGSSATY
  MDQAPSPAVCPQAPYNMYPQNPDHVLDQDGEFDLDETMDVARHVEELLRRPMDSLDSRLS
  PPAGLFTSARGSLS
• Function: Carries out a dual signal transduction and activation of transcription. Mediates cellular responses to the cytokine KITLG/SCF and other growth factors. Mediates cellular responses to ERBB4. May mediate cellular responses to activated FGFR1, FGFR2, FGFR3 and FGFR4. Binds to the GAS element and activates PRL-induced transcription. Regulates the expression of milk proteins during lactation.
• KEGG Pathway:
  ErbB sig.ling pathway (hsa04012)
  Necroptosis (hsa04217)
  JAK-STAT sig.ling pathway (hsa04630)
  Th1 and Th2 cell differentiation (hsa04658)
  Th17 cell differentiation (hsa04659)
  Prolactin sig.ling pathway (hsa04917)
  AGE-RAGE sig.ling pathway in diabetic complications (hsa04933)
  Growth hormone synthesis, secretion and action (hsa04935)
  Hepatitis B (hsa05161)
  Measles (hsa05162)
  Human T-cell leukemia virus 1 infection (hsa05166)
  Pathways in cancer (hsa05200)
  Viral carcinogenesis (hsa05203)
  Chemical carcinogenesis - receptor activation (hsa05207)
  Chronic myeloid leukemia (hsa05220)
  Acute myeloid leukemia (hsa05221)
  Non-small cell lung cancer (hsa05223)
• Reactome Pathway:
  Nuclear signaling by ERBB4 (R-HSA-1251985)
  Interleukin-7 signaling (R-HSA-1266695)
  Signaling by SCF-KIT (R-HSA-1433557)
  Signaling by cytosolic FGFR1 fusion mutants (R-HSA-1839117)
  Downstream signal transduction (R-HSA-186763)
  Signaling by Leptin (R-HSA-2586552)
  Interleukin-3, Interleukin-5 and GM-CSF signaling (R-HSA-512988)
  Interleukin-20 family signaling (R-HSA-8854691)
  Interleukin-15 signaling (R-HSA-8983432)
  Interleukin-9 signaling (R-HSA-8985947)
  Interleukin-2 signaling (R-HSA-9020558)
  Interleukin-21 signaling (R-HSA-9020958)
  Erythropoietin activates STAT5 (R-HSA-9027283)
  STAT5 Activation (R-HSA-9645135)
  Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants (R-HSA-9670439)
  Signaling by CSF3 (G-CSF) (R-HSA-9674555)
  STAT5 activation downstream of FLT3 ITD mutants (R-HSA-9702518)
  Signaling by FLT3 fusion proteins (R-HSA-9703465)
  Inactivation of CSF3 (G-CSF) signaling (R-HSA-9705462)
  Nuclear events stimulated by ALK signaling in cancer (R-HSA-9725371)
  Growth hormone receptor signaling (R-HSA-982772)
  Prolactin receptor signaling (R-HSA-1170546)

Molecular Interaction Atlas (MIA) of This DOT

44 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Undifferentiated carcinoma	DISIAZST	Definitive	Biomarker	[1]
Acute lymphocytic leukaemia	DISPX75S	Strong	Posttranslational Modification	[2]
Adenocarcinoma	DIS3IHTY	Strong	Altered Expression	[3]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[4]
Adult lymphoma	DISK8IZR	Strong	Biomarker	[5]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[6]
B-cell neoplasm	DISVY326	Strong	Genetic Variation	[7]
Breast lobular carcinoma	DISBY98Q	Strong	Biomarker	[8]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[9]
Childhood acute lymphoblastic leukemia	DISJ5D6U	Strong	Posttranslational Modification	[2]
Classic Hodgkin lymphoma	DISV1LU6	Strong	Altered Expression	[10]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[11]
Ductal breast carcinoma in situ	DISLCJY7	Strong	Biomarker	[8]
Hepatitis C virus infection	DISQ0M8R	Strong	Altered Expression	[12]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[13]
Lung carcinoma	DISTR26C	Strong	Biomarker	[14]
Lung neoplasm	DISVARNB	Strong	Biomarker	[15]
Lymphoma	DISN6V4S	Strong	Biomarker	[5]
Metastatic malignant neoplasm	DIS86UK6	Strong	Altered Expression	[16]
Myocardial ischemia	DISFTVXF	Strong	Biomarker	[17]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Biomarker	[18]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[19]
Pediatric lymphoma	DIS51BK2	Strong	Biomarker	[5]
Polycythemia vera	DISB5FPO	Strong	Altered Expression	[20]
Precancerous condition	DISV06FL	Strong	Biomarker	[8]
Prostate cancer	DISF190Y	Strong	Biomarker	[21]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[21]
Small lymphocytic lymphoma	DIS30POX	Strong	Altered Expression	[22]
Squamous cell carcinoma	DISQVIFL	Strong	Altered Expression	[23]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[24]
T-cell acute lymphoblastic leukaemia	DIS17AI2	Strong	Biomarker	[25]
Type-1 diabetes	DIS7HLUB	Strong	Biomarker	[26]
Chronic kidney disease	DISW82R7	moderate	Biomarker	[27]
Colon cancer	DISVC52G	moderate	Altered Expression	[28]
Colon carcinoma	DISJYKUO	moderate	Altered Expression	[28]
Carcinoma	DISH9F1N	Limited	Altered Expression	[29]
leukaemia	DISS7D1V	Limited	Altered Expression	[30]
Leukemia	DISNAKFL	Limited	Altered Expression	[30]
Lung cancer	DISCM4YA	Limited	Biomarker	[14]
Mastocytosis	DIS1TEE0	Limited	Biomarker	[31]
Myeloproliferative neoplasm	DIS5KAPA	Limited	Biomarker	[32]
Neoplasm	DISZKGEW	Limited	Biomarker	[30]
Prostate neoplasm	DISHDKGQ	Limited	Altered Expression	[33]
Systemic mastocytosis	DISNQ2OY	Limited	Biomarker	[31]

8 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 Signal transducer and activator of transcription 5A (STAT5A).	[34]
Marinol	DM70IK5	Approved	Marinol increases the phosphorylation of Signal transducer and activator of transcription 5A (STAT5A).	[44]
Tofacitinib	DMBS370	Approved	Tofacitinib decreases the phosphorylation of Signal transducer and activator of transcription 5A (STAT5A).	[52]
AC220	DM8Y4JS	Approved	AC220 decreases the phosphorylation of Signal transducer and activator of transcription 5A (STAT5A).	[53]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate increases the phosphorylation of Signal transducer and activator of transcription 5A (STAT5A).	[58]
AZD1480	DMLK59M	Phase 2	AZD1480 decreases the phosphorylation of Signal transducer and activator of transcription 5A (STAT5A).	[59]
PMID25656651-Compound-5	DMAI95U	Patented	PMID25656651-Compound-5 decreases the phosphorylation of Signal transducer and activator of transcription 5A (STAT5A).	[63]
NORCANTHARIDIN	DM9B6Y1	Investigative	NORCANTHARIDIN decreases the phosphorylation of Signal transducer and activator of transcription 5A (STAT5A).	[65]

24 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 Signal transducer and activator of transcription 5A (STAT5A).	[35]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Signal transducer and activator of transcription 5A (STAT5A).	[36]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Signal transducer and activator of transcription 5A (STAT5A).	[37]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Signal transducer and activator of transcription 5A (STAT5A).	[38]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Signal transducer and activator of transcription 5A (STAT5A).	[39]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of Signal transducer and activator of transcription 5A (STAT5A).	[40]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Signal transducer and activator of transcription 5A (STAT5A).	[41]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Signal transducer and activator of transcription 5A (STAT5A).	[42]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Signal transducer and activator of transcription 5A (STAT5A).	[42]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Signal transducer and activator of transcription 5A (STAT5A).	[43]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Signal transducer and activator of transcription 5A (STAT5A).	[45]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Signal transducer and activator of transcription 5A (STAT5A).	[46]
Dexamethasone	DMMWZET	Approved	Dexamethasone affects the activity of Signal transducer and activator of transcription 5A (STAT5A).	[47]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Signal transducer and activator of transcription 5A (STAT5A).	[48]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of Signal transducer and activator of transcription 5A (STAT5A).	[49]
Sorafenib	DMS8IFC	Approved	Sorafenib decreases the activity of Signal transducer and activator of transcription 5A (STAT5A).	[50]
Diphenylpyraline	DMW4X37	Approved	Diphenylpyraline increases the expression of Signal transducer and activator of transcription 5A (STAT5A).	[51]
Curcumin	DMQPH29	Phase 3	Curcumin decreases the expression of Signal transducer and activator of transcription 5A (STAT5A).	[55]
MLN4924	DMP36KD	Phase 3	MLN4924 affects the expression of Signal transducer and activator of transcription 5A (STAT5A).	[56]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Signal transducer and activator of transcription 5A (STAT5A).	[57]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Signal transducer and activator of transcription 5A (STAT5A).	[60]
Mivebresib	DMCPF90	Phase 1	Mivebresib decreases the expression of Signal transducer and activator of transcription 5A (STAT5A).	[61]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Signal transducer and activator of transcription 5A (STAT5A).	[62]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Signal transducer and activator of transcription 5A (STAT5A).	[64]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Resveratrol	DM3RWXL	Phase 3	Resveratrol affects the localization of Signal transducer and activator of transcription 5A (STAT5A).	[54]

References

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