Details of Drug Off-Target (DOT)

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

• DOT Name: Regulator of G-protein signaling 1 (RGS1)
• Synonyms: RGS1; B-cell activation protein BL34; Early response protein 1R20
• Gene Name: RGS1
• Related Disease:
  Advanced cancer
  Allergic contact dermatitis
  Burkitt lymphoma
  Melanoma
  Neoplasm
  Pediatric lymphoma
  Adult T-cell leukemia/lymphoma
  Allergic rhinitis
  Anxiety
  Anxiety disorder
  Aortic aneurysm
  Arteriosclerosis
  Arthritis
  Atherosclerosis
  Autoimmune disease
  B-cell lymphoma
  Colorectal carcinoma
  Depression
  IgA nephropathy
  Rheumatoid arthritis
  Skin disease
  T-cell leukaemia
  Vascular disease
  High blood pressure
  Osteosarcoma
  Plasma cell myeloma
  Adult lymphoma
  Lymphoma
  Adenocarcinoma
  Coeliac disease
  Type-1 diabetes
  Type-1/2 diabetes
• UniProt ID: RGS1_HUMAN
• PDB ID: 2BV1; 2GTP
• Pfam ID: PF00615
• Sequence:
  MRAAAISTPKLDKMPGMFFSANPKELKGTTHSLLDDKMQKRRPKTFGMDMKAYLRSMIPH
  LESGMKSSKSKDVLSAAEVMQWSQSLEKLLANQTGQNVFGSFLKSEFSEENIEFWLACED
  YKKTESDLLPCKAEEIYKAFVHSDAAKQINIDFRTRESTAKKIKAPTPTCFDEAQKVIYT
  LMEKDSYPRFLKSDIYLNLLNDLQANSLK
• Function: Regulates G protein-coupled receptor signaling cascades, including signaling downstream of the N-formylpeptide chemoattractant receptors and leukotriene receptors. Inhibits B cell chemotaxis toward CXCL12. Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits thereby driving them into their inactive GDP-bound form.
• Tissue Specificity: Detected in peripheral blood monocytes . Expression is relatively low in B-cells and chronic lymphocytic leukemia B-cells; however, in other types of malignant B-cell such as non-Hodgkin lymphoma and hairy cell leukemia, expression is constitutively high .
• Reactome Pathway:
  G alpha (i) signalling events (R-HSA-418594)
  G alpha (q) signalling events (R-HSA-416476)

Molecular Interaction Atlas (MIA) of This DOT

32 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Definitive	Biomarker	[1]
Allergic contact dermatitis	DISFFVF9	Definitive	Biomarker	[2]
Burkitt lymphoma	DIS9D5XU	Definitive	Altered Expression	[3]
Melanoma	DIS1RRCY	Definitive	Biomarker	[1]
Neoplasm	DISZKGEW	Definitive	Biomarker	[4]
Pediatric lymphoma	DIS51BK2	Definitive	Altered Expression	[3]
Adult T-cell leukemia/lymphoma	DIS882XU	Strong	Biomarker	[5]
Allergic rhinitis	DIS3U9HN	Strong	Biomarker	[6]
Anxiety	DISIJDBA	Strong	Genetic Variation	[7]
Anxiety disorder	DISBI2BT	Strong	Genetic Variation	[7]
Aortic aneurysm	DISQ5KRA	Strong	Biomarker	[8]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[8]
Arthritis	DIST1YEL	Strong	Biomarker	[9]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[8]
Autoimmune disease	DISORMTM	Strong	Biomarker	[10]
B-cell lymphoma	DISIH1YQ	Strong	Altered Expression	[11]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[12]
Depression	DIS3XJ69	Strong	Genetic Variation	[7]
IgA nephropathy	DISZ8MTK	Strong	Genetic Variation	[13]
Rheumatoid arthritis	DISTSB4J	Strong	Biomarker	[9]
Skin disease	DISDW8R6	Strong	Biomarker	[14]
T-cell leukaemia	DISJ6YIF	Strong	Biomarker	[5]
Vascular disease	DISVS67S	Strong	Biomarker	[8]
High blood pressure	DISY2OHH	moderate	Biomarker	[15]
Osteosarcoma	DISLQ7E2	moderate	Biomarker	[16]
Plasma cell myeloma	DIS0DFZ0	moderate	Altered Expression	[17]
Adult lymphoma	DISK8IZR	Disputed	Altered Expression	[3]
Lymphoma	DISN6V4S	Disputed	Altered Expression	[3]
Adenocarcinoma	DIS3IHTY	Limited	Biomarker	[18]
Coeliac disease	DISIY60C	Limited	Genetic Variation	[19]
Type-1 diabetes	DIS7HLUB	Limited	Biomarker	[20]
Type-1/2 diabetes	DISIUHAP	Limited	Biomarker	[20]

2 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 Regulator of G-protein signaling 1 (RGS1).	[21]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Regulator of G-protein signaling 1 (RGS1).	[39]

22 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 Regulator of G-protein signaling 1 (RGS1).	[22]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of Regulator of G-protein signaling 1 (RGS1).	[23]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of Regulator of G-protein signaling 1 (RGS1).	[14]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Regulator of G-protein signaling 1 (RGS1).	[25]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Regulator of G-protein signaling 1 (RGS1).	[26]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Regulator of G-protein signaling 1 (RGS1).	[27]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Regulator of G-protein signaling 1 (RGS1).	[28]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Regulator of G-protein signaling 1 (RGS1).	[29]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil affects the expression of Regulator of G-protein signaling 1 (RGS1).	[23]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Regulator of G-protein signaling 1 (RGS1).	[30]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Regulator of G-protein signaling 1 (RGS1).	[31]
Irinotecan	DMP6SC2	Approved	Irinotecan increases the expression of Regulator of G-protein signaling 1 (RGS1).	[32]
Nicotine	DMWX5CO	Approved	Nicotine increases the expression of Regulator of G-protein signaling 1 (RGS1).	[33]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of Regulator of G-protein signaling 1 (RGS1).	[34]
Pioglitazone	DMKJ485	Approved	Pioglitazone decreases the expression of Regulator of G-protein signaling 1 (RGS1).	[35]
Cholecalciferol	DMGU74E	Approved	Cholecalciferol affects the expression of Regulator of G-protein signaling 1 (RGS1).	[36]
DNCB	DMDTVYC	Phase 2	DNCB increases the expression of Regulator of G-protein signaling 1 (RGS1).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Regulator of G-protein signaling 1 (RGS1).	[33]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Regulator of G-protein signaling 1 (RGS1).	[38]
Eugenol	DM7US1H	Patented	Eugenol increases the expression of Regulator of G-protein signaling 1 (RGS1).	[2]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Regulator of G-protein signaling 1 (RGS1).	[30]
Phencyclidine	DMQBEYX	Investigative	Phencyclidine increases the expression of Regulator of G-protein signaling 1 (RGS1).	[40]

References

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• [36] Targeting iron homeostasis induces cellular differentiation and synergizes with differentiating agents in acute myeloid leukemia. J Exp Med. 2010 Apr 12;207(4):731-50. doi: 10.1084/jem.20091488. Epub 2010 Apr 5.
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• [38] Targeting MYC dependence in cancer by inhibiting BET bromodomains. Proc Natl Acad Sci U S A. 2011 Oct 4;108(40):16669-74. doi: 10.1073/pnas.1108190108. Epub 2011 Sep 26.
• [39] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
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