Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTY183WJ)

• DOT Name: Suppressor of cytokine signaling 3 (SOCS3)
• Synonyms: SOCS-3; Cytokine-inducible SH2 protein 3; CIS-3; STAT-induced STAT inhibitor 3; SSI-3
• Gene Name: SOCS3
• UniProt ID: SOCS3_HUMAN
• Pfam ID: PF00017
• Sequence:
  MVTHSKFPAAGMSRPLDTSLRLKTFSSKSEYQLVVNAVRKLQESGFYWSAVTGGEANLLL
  SAEPAGTFLIRDSSDQRHFFTLSVKTQSGTKNLRIQCEGGSFSLQSDPRSTQPVPRFDCV
  LKLVHHYMPPPGAPSFPSPPTEPSSEVPEQPSAQPLPGSPPRRAYYIYSGGEKIPLVLSR
  PLSSNVATLQHLCRKTVNGHLDSYEKVTQLPGPIREFLDQYDAPL
• Function: SOCS family proteins form part of a classical negative feedback system that regulates cytokine signal transduction. SOCS3 is involved in negative regulation of cytokines that signal through the JAK/STAT pathway. Inhibits cytokine signal transduction by binding to tyrosine kinase receptors including IL6ST/gp130, LIF, erythropoietin, insulin, IL12, GCSF and leptin receptors. Binding to JAK2 inhibits its kinase activity and regulates IL6 signaling. Suppresses fetal liver erythropoiesis. Regulates onset and maintenance of allergic responses mediated by T-helper type 2 cells. Probable substrate recognition component of a SCF-like ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins.
• Tissue Specificity: Widely expressed with high expression in heart, placenta, skeletal muscle, peripheral blood leukocytes, fetal and adult lung, and fetal liver and kidney. Lower levels in thymus.
• KEGG Pathway:
  Ubiquitin mediated proteolysis (hsa04120)
  Osteoclast differentiation (hsa04380)
  JAK-STAT sig.ling pathway (hsa04630)
  TNF sig.ling pathway (hsa04668)
  Insulin sig.ling pathway (hsa04910)
  Prolactin sig.ling pathway (hsa04917)
  Adipocytokine sig.ling pathway (hsa04920)
  Type II diabetes mellitus (hsa04930)
  Insulin resistance (hsa04931)
  Non-alcoholic fatty liver disease (hsa04932)
  Growth hormone synthesis, secretion and action (hsa04935)
  Hepatitis C (hsa05160)
  Influenza A (hsa05164)
  Herpes simplex virus 1 infection (hsa05168)
• Reactome Pathway:
  Signaling by Leptin (R-HSA-2586552)
  Interleukin-4 and Interleukin-13 signaling (R-HSA-6785807)
  Interferon gamma signaling (R-HSA-877300)
  Regulation of IFNG signaling (R-HSA-877312)
  PTK6 Activates STAT3 (R-HSA-8849474)
  RUNX1 regulates transcription of genes involved in differentiation of keratinocytes (R-HSA-8939242)
  Neddylation (R-HSA-8951664)
  Interferon alpha/beta signaling (R-HSA-909733)
  Regulation of IFNA/IFNB signaling (R-HSA-912694)
  Signaling by CSF3 (G-CSF) (R-HSA-9674555)
  Inactivation of CSF3 (G-CSF) signaling (R-HSA-9705462)
  Growth hormone receptor signaling (R-HSA-982772)
  Antigen processing (R-HSA-983168)
  Interleukin-6 signaling (R-HSA-1059683)

Molecular Interaction Atlas (MIA) of This DOT

2 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 Suppressor of cytokine signaling 3 (SOCS3).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Suppressor of cytokine signaling 3 (SOCS3).	[26]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Suppressor of cytokine signaling 3 (SOCS3).	[2]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Suppressor of cytokine signaling 3 (SOCS3).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Suppressor of cytokine signaling 3 (SOCS3).	[4]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Suppressor of cytokine signaling 3 (SOCS3).	[5]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of Suppressor of cytokine signaling 3 (SOCS3).	[6]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Suppressor of cytokine signaling 3 (SOCS3).	[7]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Suppressor of cytokine signaling 3 (SOCS3).	[8]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Suppressor of cytokine signaling 3 (SOCS3).	[9]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Suppressor of cytokine signaling 3 (SOCS3).	[10]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Suppressor of cytokine signaling 3 (SOCS3).	[11]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of Suppressor of cytokine signaling 3 (SOCS3).	[8]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the expression of Suppressor of cytokine signaling 3 (SOCS3).	[12]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Suppressor of cytokine signaling 3 (SOCS3).	[13]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Suppressor of cytokine signaling 3 (SOCS3).	[14]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of Suppressor of cytokine signaling 3 (SOCS3).	[15]
Malathion	DMXZ84M	Approved	Malathion decreases the expression of Suppressor of cytokine signaling 3 (SOCS3).	[16]
Azacitidine	DMTA5OE	Approved	Azacitidine affects the expression of Suppressor of cytokine signaling 3 (SOCS3).	[17]
Simvastatin	DM30SGU	Approved	Simvastatin increases the expression of Suppressor of cytokine signaling 3 (SOCS3).	[18]
Ibuprofen	DM8VCBE	Approved	Ibuprofen affects the expression of Suppressor of cytokine signaling 3 (SOCS3).	[19]
Diphenylpyraline	DMW4X37	Approved	Diphenylpyraline decreases the expression of Suppressor of cytokine signaling 3 (SOCS3).	[20]
Rofecoxib	DM3P5DA	Approved	Rofecoxib increases the expression of Suppressor of cytokine signaling 3 (SOCS3).	[19]
Tofacitinib	DMBS370	Approved	Tofacitinib decreases the expression of Suppressor of cytokine signaling 3 (SOCS3).	[21]
Pyrimethamine	DM5X7VY	Approved	Pyrimethamine decreases the expression of Suppressor of cytokine signaling 3 (SOCS3).	[22]
Fedratinib	DM4ZBK6	Approved	Fedratinib decreases the expression of Suppressor of cytokine signaling 3 (SOCS3).	[22]
Isoflavone	DM7U58J	Phase 4	Isoflavone increases the expression of Suppressor of cytokine signaling 3 (SOCS3).	[23]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Suppressor of cytokine signaling 3 (SOCS3).	[8]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Suppressor of cytokine signaling 3 (SOCS3).	[24]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Suppressor of cytokine signaling 3 (SOCS3).	[25]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of Suppressor of cytokine signaling 3 (SOCS3).	[8]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate increases the expression of Suppressor of cytokine signaling 3 (SOCS3).	[23]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Suppressor of cytokine signaling 3 (SOCS3).	[27]
PF-3758309	DM36PKZ	Phase 1	PF-3758309 decreases the expression of Suppressor of cytokine signaling 3 (SOCS3).	[28]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Suppressor of cytokine signaling 3 (SOCS3).	[29]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Suppressor of cytokine signaling 3 (SOCS3).	[30]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Suppressor of cytokine signaling 3 (SOCS3).	[31]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Suppressor of cytokine signaling 3 (SOCS3).	[32]
Hexadecanoic acid	DMWUXDZ	Investigative	Hexadecanoic acid affects the expression of Suppressor of cytokine signaling 3 (SOCS3).	[33]
Phencyclidine	DMQBEYX	Investigative	Phencyclidine increases the expression of Suppressor of cytokine signaling 3 (SOCS3).	[34]
Forskolin	DM6ITNG	Investigative	Forskolin increases the expression of Suppressor of cytokine signaling 3 (SOCS3).	[23]
Apigenin	DMI3491	Investigative	Apigenin increases the expression of Suppressor of cytokine signaling 3 (SOCS3).	[23]
1,6-hexamethylene diisocyanate	DMLB3RT	Investigative	1,6-hexamethylene diisocyanate affects the expression of Suppressor of cytokine signaling 3 (SOCS3).	[35]
Flavone	DMEQH6J	Investigative	Flavone increases the expression of Suppressor of cytokine signaling 3 (SOCS3).	[23]
Fenthion	DMKEG49	Investigative	Fenthion increases the expression of Suppressor of cytokine signaling 3 (SOCS3).	[36]
ROLIPRAM	DMJ03UM	Investigative	ROLIPRAM increases the expression of Suppressor of cytokine signaling 3 (SOCS3).	[23]
4-[1-(4-hydroxyphenyl)-2-phenylbut-1-enyl]phenol	DMTMLXU	Investigative	4-[1-(4-hydroxyphenyl)-2-phenylbut-1-enyl]phenol decreases the expression of Suppressor of cytokine signaling 3 (SOCS3).	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
MG-132	DMKA2YS	Preclinical	MG-132 decreases the degradation of Suppressor of cytokine signaling 3 (SOCS3).	[23]

References

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