Details of Drug Off-Target (DOT)

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

• DOT Name: Nuclear receptor coactivator 2 (NCOA2)
• Synonyms: NCoA-2; Class E basic helix-loop-helix protein 75; bHLHe75; Transcriptional intermediary factor 2; hTIF2
• Gene Name: NCOA2
• Related Disease:
  Acute biphenotypic leukaemia
  Acute leukaemia
  Acute monocytic leukemia
  Acute myelomonocytic leukemia M4
  Advanced cancer
  Androgen insensitivity syndrome
  Carcinoma of liver and intrahepatic biliary tract
  Chondrosarcoma
  Colorectal carcinoma
  Endometrial cancer
  Endometrial carcinoma
  Glucocorticoid resistance
  Hepatocellular carcinoma
  Hereditary chronic pancreatitis
  Hyperglycemia
  Hypothyroidism
  Leiomyoma
  Leukemia
  Liver cancer
  Lung carcinoma
  Malabsorption syndrome
  Mixed phenotype acute leukemia
  Multiple sclerosis
  Non-alcoholic fatty liver disease
  Non-alcoholic steatohepatitis
  Obesity
  Uterine fibroids
  Bone osteosarcoma
  Ductal breast carcinoma in situ
  Osteosarcoma
  Kaposi sarcoma
  Acute myelogenous leukaemia
  Breast neoplasm
  Castration-resistant prostate carcinoma
  Her2-receptor negative breast cancer
  leukaemia
  Malignant soft tissue neoplasm
  Prostate neoplasm
  Rhabdomyosarcoma
  Sarcoma
• UniProt ID: NCOA2_HUMAN
• PDB ID: 1GWQ ; 1GWR ; 1M2Z ; 1MV9 ; 1MVC ; 1MZN ; 1P93 ; 1T63 ; 1T65 ; 1UHL ; 1YOK ; 1ZDT ; 1ZDU ; 1ZKY ; 2AO6 ; 2B1V ; 2B1Z ; 2B23 ; 2FAI ; 2G44 ; 2G5O ; 2LDC ; 2P15 ; 2P1T ; 2P1U ; 2P1V ; 2Q7J ; 2Q7L ; 2YJD ; 2ZXZ ; 2ZY0 ; 3A9E ; 3CLD ; 3DZU ; 3DZY ; 3E00 ; 3E7C ; 3E94 ; 3ERD ; 3FUG ; 3GN8 ; 3K22 ; 3K23 ; 3KWY ; 3KYT ; 3L0E ; 3L0J ; 3L0L ; 3O1D ; 3O1E ; 3OAP ; 3OZJ ; 3PCU ; 3PLZ ; 3Q95 ; 3R5M ; 3UP0 ; 3UP3 ; 4CSJ ; 4DOS ; 4E2J ; 4FHH ; 4FHI ; 4IA1 ; 4IA2 ; 4IA3 ; 4IA7 ; 4IQR ; 4IU7 ; 4IUI ; 4IV2 ; 4IV4 ; 4IVW ; 4IVY ; 4IW6 ; 4IW8 ; 4IWC ; 4IWF ; 4K4J ; 4K6I ; 4M8E ; 4M8H ; 4NIE ; 4NQA ; 4OC7 ; 4P6W ; 4P6X ; 4PLD ; 4PLE ; 4POH ; 4POJ ; 4PP3 ; 4PP5 ; 4PP6 ; 4PPP ; 4PPS ; 4PXM ; 4Q0A ; 4Q13 ; 4QE8 ; 4RFW ; 4RMC ; 4RMD ; 4RME ; 4RUO ; 4UDC ; 4UDD ; 4WG0 ; 4ZN7 ; 4ZN9 ; 4ZNH ; 4ZNS ; 4ZNT ; 4ZNU ; 4ZNV ; 4ZNW ; 4ZO1 ; 4ZSH ; 5APH ; 5APJ ; 5DI7 ; 5DID ; 5DIE ; 5DIG ; 5DK9 ; 5DKB ; 5DKE ; 5DKG ; 5DKS ; 5DL4 ; 5DLR ; 5DMC ; 5DMF ; 5DP0 ; 5DRJ ; 5DRM ; 5DTV ; 5DU5 ; 5DUE ; 5DUG ; 5DUH ; 5DVS ; 5DVV ; 5DWE ; 5DWG ; 5DWI ; 5DWJ ; 5DX3 ; 5DXB ; 5DXE ; 5DXG ; 5DXK ; 5DXM ; 5DXP ; 5DXQ ; 5DXR ; 5DY8 ; 5DYB ; 5DYD ; 5DZ0 ; 5DZ1 ; 5DZ3 ; 5DZH ; 5DZI ; 5E0W ; 5E0X ; 5E14 ; 5E15 ; 5E19 ; 5E1C ; 5EC9 ; 5EGV ; 5EHJ ; 5EI1 ; 5EIT ; 5G3J ; 5G42 ; 5G43 ; 5G44 ; 5G45 ; 5G46 ; 5G5W ; 5H1E ; 5HYR ; 5I4V ; 5IAW ; 5ICK ; 5KCC ; 5KCD ; 5KCE ; 5KCF ; 5KCT ; 5KCU ; 5KCW ; 5KD9 ; 5KR9 ; 5KRA ; 5KRC ; 5KRF ; 5KRH ; 5KRI ; 5KRJ ; 5KRK ; 5KRL ; 5KRM ; 5KRO ; 5L11 ; 5LGA ; 5LYQ ; 5MK4 ; 5NFP ; 5NFT ; 5NI5 ; 5NI7 ; 5NI8 ; 5NIB ; 5Q17 ; 5SYZ ; 5T1Z ; 5TLD ; 5TLF ; 5TLG ; 5TLL ; 5TLM ; 5TLO ; 5TLP ; 5TLT ; 5TLU ; 5TLV ; 5TLX ; 5TLY ; 5TM1 ; 5TM2 ; 5TM3 ; 5TM4 ; 5TM5 ; 5TM6 ; 5TM7 ; 5TM8 ; 5TM9 ; 5TML ; 5TMM ; 5TMO ; 5TMQ ; 5TMR ; 5TMS ; 5TMT ; 5TMU ; 5TMV ; 5TMW ; 5TMZ ; 5TN1 ; 5TN3 ; 5TN4 ; 5TN5 ; 5TN6 ; 5TN7 ; 5TN8 ; 5U2D ; 5UAN ; 5VB3 ; 5VB5 ; 5VB6 ; 5VB7 ; 5VQK ; 5VQL ; 5WGQ ; 5WZX ; 5XPL ; 5Y1J ; 5Y49 ; 5YP5 ; 5YXB ; 5YXD ; 5YXJ ; 5YXL ; 5Z12 ; 6CZN ; 6D0F ; 6EL6 ; 6EL7 ; 6EL9 ; 6ESN ; 6HL1 ; 6KKB ; 6KKE ; 6KNU ; 6KNV ; 6KNW ; 6LB4 ; 6LB5 ; 6LB6 ; 6LIT ; 6OQX ; 6OQY ; 6OR1 ; 6R7A ; 6R7J ; 6R7K ; 6SJM ; 6STI ; 6VC2 ; 6VIF ; 7A77 ; 7A78 ; 7A79 ; 7APO ; 7B88 ; 7B9O ; 7BK4 ; 7D42 ; 7JHD ; 7JYD ; 7JYE ; 7KCO ; 7NEL ; 7NFB ; 7NKE ; 7OFI ; 7OFK ; 7PDQ ; 7PDT ; 7RAE ; 7RAF ; 7RKE ; 7SFO ; 7T2X ; 7TT8 ; 7UW2 ; 7UW4 ; 7VUE ; 7W3P ; 7W3Q ; 7WLX ; 7WMG ; 7WMH ; 7WMJ ; 7WML ; 7WMN ; 7WMO ; 7YMK ; 8DAF ; 8EV1 ; 8EV2 ; 8F8M ; 8PZ7 ; 8PZ9
• Pfam ID: PF07469 ; PF16279 ; PF16665 ; PF08815 ; PF00989 ; PF14598 ; PF08832
• Sequence:
  MSGMGENTSDPSRAETRKRKECPDQLGPSPKRNTEKRNREQENKYIEELAELIFANFNDI
  DNFNFKPDKCAILKETVKQIRQIKEQEKAAAANIDEVQKSDVSSTGQGVIDKDALGPMML
  EALDGFFFVVNLEGNVVFVSENVTQYLRYNQEELMNKSVYSILHVGDHTEFVKNLLPKSI
  VNGGSWSGEPPRRNSHTFNCRMLVKPLPDSEEEGHDNQEAHQKYETMQCFAVSQPKSIKE
  EGEDLQSCLICVARRVPMKERPVLPSSESFTTRQDLQGKITSLDTSTMRAAMKPGWEDLV
  RRCIQKFHAQHEGESVSYAKRHHHEVLRQGLAFSQIYRFSLSDGTLVAAQTKSKLIRSQT
  TNEPQLVISLHMLHREQNVCVMNPDLTGQTMGKPLNPISSNSPAHQALCSGNPGQDMTLS
  SNINFPINGPKEQMGMPMGRFGGSGGMNHVSGMQATTPQGSNYALKMNSPSQSSPGMNPG
  QPTSMLSPRHRMSPGVAGSPRIPPSQFSPAGSLHSPVGVCSSTGNSHSYTNSSLNALQAL
  SEGHGVSLGSSLASPDLKMGNLQNSPVNMNPPPLSKMGSLDSKDCFGLYGEPSEGTTGQA
  ESSCHPGEQKETNDPNLPPAVSSERADGQSRLHDSKGQTKLLQLLTTKSDQMEPSPLASS
  LSDTNKDSTGSLPGSGSTHGTSLKEKHKILHRLLQDSSSPVDLAKLTAEATGKDLSQESS
  STAPGSEVTIKQEPVSPKKKENALLRYLLDKDDTKDIGLPEITPKLERLDSKTDPASNTK
  LIAMKTEKEEMSFEPGDQPGSELDNLEEILDDLQNSQLPQLFPDTRPGAPAGSVDKQAII
  NDLMQLTAENSPVTPVGAQKTALRISQSTFNNPRPGQLGRLLPNQNLPLDITLQSPTGAG
  PFPPIRNSSPYSVIPQPGMMGNQGMIGNQGNLGNSSTGMIGNSASRPTMPSGEWAPQSSA
  VRVTCAATTSAMNRPVQGGMIRNPAASIPMRPSSQPGQRQTLQSQVMNIGPSELEMNMGG
  PQYSQQQAPPNQTAPWPESILPIDQASFASQNRQPFGSSPDDLLCPHPAAESPSDEGALL
  DQLYLALRNFDGLEEIDRALGIPELVSQSQAVDPEQFSSQDSNIMLEQKAPVFPQQYASQ
  AQMAQGSYSPMQDPNFHTMGQRPSYATLRMQPRPGLRPTGLVQNQPNQLRLQLQHRLQAQ
  QNRQPLMNQISNVSNVNLTLRPGVPTQAPINAQMLAQRQREILNQHLRQRQMHQQQQVQQ
  RTLMMRGQGLNMTPSMVAPSGMPATMSNPRIPQANAQQFPFPPNYGISQQPDPGFTGATT
  PQSPLMSPRMAHTQSPMMQQSQANPAYQAPSDINGWAQGNMGGNSMFSQQSPPHFGQQAN
  TSMYSNNMNINVSMATNTGGMSSMNQMTGQISMTSVTSVPTSGLSSMGPEQVNDPALRGG
  NLFPNQLPGMDMIKQEGDTTRKYC
• Function: Transcriptional coactivator for steroid receptors and nuclear receptors. Coactivator of the steroid binding domain (AF-2) but not of the modulating N-terminal domain (AF-1). Required with NCOA1 to control energy balance between white and brown adipose tissues. Critical regulator of glucose metabolism regulation, acts as a RORA coactivator to specifically modulate G6PC1 expression. Involved in the positive regulation of the transcriptional activity of the glucocorticoid receptor NR3C1 by sumoylation enhancer RWDD3. Positively regulates the circadian clock by acting as a transcriptional coactivator for the CLOCK-BMAL1 heterodimer.
• KEGG Pathway:
  Estrogen sig.ling pathway (hsa04915)
  Thyroid hormone sig.ling pathway (hsa04919)
• Reactome Pathway:
  BMAL1 (R-HSA-1368108)
  Recycling of bile acids and salts (R-HSA-159418)
  Synthesis of bile acids and bile salts (R-HSA-192105)
  Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol (R-HSA-193368)
  Synthesis of bile acids and bile salts via 27-hydroxycholesterol (R-HSA-193807)
  PPARA activates gene expression (R-HSA-1989781)
  Endogenous sterols (R-HSA-211976)
  Transcriptional activation of mitochondrial biogenesis (R-HSA-2151201)
  Activation of gene expression by SREBF (SREBP) (R-HSA-2426168)
  HATs acetylate histones (R-HSA-3214847)
  Transcriptional regulation of white adipocyte differentiation (R-HSA-381340)
  SUMOylation of transcription cofactors (R-HSA-3899300)
  Regulation of lipid metabolism by PPARalpha (R-HSA-400206)
  Circadian Clock (R-HSA-400253)
  Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3 (R-HSA-5625886)
  Estrogen-dependent gene expression (R-HSA-9018519)
  Cytoprotection by HMOX1 (R-HSA-9707564)
  Heme signaling (R-HSA-9707616)
  RORA activates gene expression (R-HSA-1368082)

Molecular Interaction Atlas (MIA) of This DOT

40 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute biphenotypic leukaemia	DISWE1R7	Strong	Genetic Variation	[1]
Acute leukaemia	DISDQFDI	Strong	Biomarker	[2]
Acute monocytic leukemia	DIS28NEL	Strong	Biomarker	[3]
Acute myelomonocytic leukemia M4	DISRRMV2	Strong	Genetic Variation	[4]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[5]
Androgen insensitivity syndrome	DISUZBBO	Strong	Genetic Variation	[6]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Strong	Biomarker	[7]
Chondrosarcoma	DIS4I7JB	Strong	Biomarker	[8]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[9]
Endometrial cancer	DISW0LMR	Strong	Biomarker	[5]
Endometrial carcinoma	DISXR5CY	Strong	Biomarker	[5]
Glucocorticoid resistance	DIS3HNXT	Strong	Genetic Variation	[10]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[11]
Hereditary chronic pancreatitis	DISF0J1Q	Strong	Altered Expression	[12]
Hyperglycemia	DIS0BZB5	Strong	Altered Expression	[13]
Hypothyroidism	DISR0H6D	Strong	Altered Expression	[14]
Leiomyoma	DISLDDFN	Strong	Altered Expression	[15]
Leukemia	DISNAKFL	Strong	Biomarker	[16]
Liver cancer	DISDE4BI	Strong	Biomarker	[7]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[17]
Malabsorption syndrome	DISGMUVS	Strong	Genetic Variation	[18]
Mixed phenotype acute leukemia	DISNCHV9	Strong	Genetic Variation	[1]
Multiple sclerosis	DISB2WZI	Strong	Genetic Variation	[19]
Non-alcoholic fatty liver disease	DISDG1NL	Strong	Biomarker	[11]
Non-alcoholic steatohepatitis	DIST4788	Strong	Biomarker	[11]
Obesity	DIS47Y1K	Strong	Genetic Variation	[20]
Uterine fibroids	DISBZRMJ	Strong	Altered Expression	[15]
Bone osteosarcoma	DIST1004	moderate	Altered Expression	[21]
Ductal breast carcinoma in situ	DISLCJY7	moderate	Altered Expression	[22]
Osteosarcoma	DISLQ7E2	moderate	Altered Expression	[21]
Kaposi sarcoma	DISC1H1Z	Disputed	Biomarker	[23]
Acute myelogenous leukaemia	DISCSPTN	Limited	Biomarker	[16]
Breast neoplasm	DISNGJLM	Limited	Biomarker	[24]
Castration-resistant prostate carcinoma	DISVGAE6	Limited	Biomarker	[25]
Her2-receptor negative breast cancer	DISS605N	Limited	Altered Expression	[26]
leukaemia	DISS7D1V	Limited	Biomarker	[16]
Malignant soft tissue neoplasm	DISTC6NO	Limited	Biomarker	[27]
Prostate neoplasm	DISHDKGQ	Limited	Biomarker	[28]
Rhabdomyosarcoma	DISNR7MS	Limited	Genetic Variation	[29]
Sarcoma	DISZDG3U	Limited	Biomarker	[27]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Calcitriol	DM8ZVJ7	Approved	Nuclear receptor coactivator 2 (NCOA2) increases the response to substance of Calcitriol.	[48]

5 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 Nuclear receptor coactivator 2 (NCOA2).	[30]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Nuclear receptor coactivator 2 (NCOA2).	[41]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Nuclear receptor coactivator 2 (NCOA2).	[42]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Nuclear receptor coactivator 2 (NCOA2).	[42]
Hexadecanoic acid	DMWUXDZ	Investigative	Hexadecanoic acid increases the phosphorylation of Nuclear receptor coactivator 2 (NCOA2).	[46]

17 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 Nuclear receptor coactivator 2 (NCOA2).	[31]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Nuclear receptor coactivator 2 (NCOA2).	[32]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Nuclear receptor coactivator 2 (NCOA2).	[33]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Nuclear receptor coactivator 2 (NCOA2).	[34]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Nuclear receptor coactivator 2 (NCOA2).	[35]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Nuclear receptor coactivator 2 (NCOA2).	[36]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Nuclear receptor coactivator 2 (NCOA2).	[37]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Nuclear receptor coactivator 2 (NCOA2).	[38]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the expression of Nuclear receptor coactivator 2 (NCOA2).	[34]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Nuclear receptor coactivator 2 (NCOA2).	[39]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Nuclear receptor coactivator 2 (NCOA2).	[36]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Nuclear receptor coactivator 2 (NCOA2).	[38]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Nuclear receptor coactivator 2 (NCOA2).	[40]
Geldanamycin	DMS7TC5	Discontinued in Phase 2	Geldanamycin increases the expression of Nuclear receptor coactivator 2 (NCOA2).	[43]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Nuclear receptor coactivator 2 (NCOA2).	[44]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Nuclear receptor coactivator 2 (NCOA2).	[45]
OXYBENZONE	DMMZYX6	Investigative	OXYBENZONE increases the expression of Nuclear receptor coactivator 2 (NCOA2).	[47]

References

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• [39] Dexamethasone controls aryl hydrocarbon receptor (AhR)-mediated CYP1A1 and CYP1A2 expression and activity in primary cultures of human hepatocytes. Chem Biol Interact. 2009 May 15;179(2-3):288-96.
• [40] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
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• [42] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
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