Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT97RQQM)

• DOT Name: Runt-related transcription factor 2 (RUNX2)
• Synonyms: Acute myeloid leukemia 3 protein; Core-binding factor subunit alpha-1; CBF-alpha-1; Oncogene AML-3; Osteoblast-specific transcription factor 2; OSF-2; Polyomavirus enhancer-binding protein 2 alpha A subunit; PEA2-alpha A; PEBP2-alpha A; SL3-3 enhancer factor 1 alpha A subunit; SL3/AKV core-binding factor alpha A subunit
• Gene Name: RUNX2
• Related Disease:
  Cleidocranial dysplasia 1
  Metaphyseal dysplasia-maxillary hypoplasia-brachydacty syndrome
• UniProt ID: RUNX2_HUMAN
• PDB ID: 6VG8; 6VGD; 6VGE; 6VGG
• Pfam ID: PF00853 ; PF08504
• Sequence:
  MASNSLFSTVTPCQQNFFWDPSTSRRFSPPSSSLQPGKMSDVSPVVAAQQQQQQQQQQQQ
  QQQQQQQQQQQEAAAAAAAAAAAAAAAAAVPRLRPPHDNRTMVEIIADHPAELVRTDSPN
  FLCSVLPSHWRCNKTLPVAFKVVALGEVPDGTVVTVMAGNDENYSAELRNASAVMKNQVA
  RFNDLRFVGRSGRGKSFTLTITVFTNPPQVATYHRAIKVTVDGPREPRRHRQKLDDSKPS
  LFSDRLSDLGRIPHPSMRVGVPPQNPRPSLNSAPSPFNPQGQSQITDPRQAQSSPPWSYD
  QSYPSYLSQMTSPSIHSTTPLSSTRGTGLPAITDVPRRISDDDTATSDFCLWPSTLSKKS
  QAGASELGPFSDPRQFPSISSLTESRFSNPRMHYPATFTYTPPVTSGMSLGMSATTHYHT
  YLPPPYPGSSQSQSGPFQTSSTPYLYYGTSSGSYQFPMVPGGDRSPSRMLPPCTTTSNGS
  TLLNPNLPNQNDGVDADGSHSSSPTVLNSSGRMDESVWRPY
• Function: Transcription factor involved in osteoblastic differentiation and skeletal morphogenesis. Essential for the maturation of osteoblasts and both intramembranous and endochondral ossification. CBF binds to the core site, 5'-PYGPYGGT-3', of a number of enhancers and promoters, including murine leukemia virus, polyomavirus enhancer, T-cell receptor enhancers, osteocalcin, osteopontin, bone sialoprotein, alpha 1(I) collagen, LCK, IL-3 and GM-CSF promoters. In osteoblasts, supports transcription activation: synergizes with SPEN/MINT to enhance FGFR2-mediated activation of the osteocalcin FGF-responsive element (OCFRE). Inhibits KAT6B-dependent transcriptional activation.
• Tissue Specificity: Specifically expressed in osteoblasts.
• KEGG Pathway:
  Parathyroid hormone synthesis, secretion and action (hsa04928)
  Transcriptio.l misregulation in cancer (hsa05202)
• Reactome Pathway:
  Transcriptional regulation by RUNX2 (R-HSA-8878166)
  RUNX1 regulates transcription of genes involved in differentiation of myeloid cells (R-HSA-8939246)
  Regulation of RUNX2 expression and activity (R-HSA-8939902)
  RUNX2 regulates osteoblast differentiation (R-HSA-8940973)
  RUNX2 regulates chondrocyte maturation (R-HSA-8941284)
  RUNX2 regulates bone development (R-HSA-8941326)
  RUNX2 regulates genes involved in cell migration (R-HSA-8941332)
  RUNX2 regulates genes involved in differentiation of myeloid cells (R-HSA-8941333)
  YAP1- and WWTR1 (TAZ)-stimulated gene expression (R-HSA-2032785)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cleidocranial dysplasia 1	DIS2OHLA	Definitive	Autosomal dominant	[1]
Metaphyseal dysplasia-maxillary hypoplasia-brachydacty syndrome	DISS03DP	Strong	Autosomal dominant	[2]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Methotrexate	DM2TEOL	Approved	Runt-related transcription factor 2 (RUNX2) decreases the response to substance of Methotrexate.	[41]
(S)-Norfluoxetine	DM8ZTPF	Investigative	Runt-related transcription factor 2 (RUNX2) increases the Fracture ADR of (S)-Norfluoxetine.	[42]

3 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 Runt-related transcription factor 2 (RUNX2).	[3]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Runt-related transcription factor 2 (RUNX2).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Runt-related transcription factor 2 (RUNX2).	[30]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Runt-related transcription factor 2 (RUNX2).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Runt-related transcription factor 2 (RUNX2).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Runt-related transcription factor 2 (RUNX2).	[6]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Runt-related transcription factor 2 (RUNX2).	[7]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Runt-related transcription factor 2 (RUNX2).	[9]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Runt-related transcription factor 2 (RUNX2).	[10]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Runt-related transcription factor 2 (RUNX2).	[11]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Runt-related transcription factor 2 (RUNX2).	[12]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Runt-related transcription factor 2 (RUNX2).	[13]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Runt-related transcription factor 2 (RUNX2).	[14]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Runt-related transcription factor 2 (RUNX2).	[15]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Runt-related transcription factor 2 (RUNX2).	[16]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Runt-related transcription factor 2 (RUNX2).	[17]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the expression of Runt-related transcription factor 2 (RUNX2).	[18]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of Runt-related transcription factor 2 (RUNX2).	[19]
Cidofovir	DMA13GD	Approved	Cidofovir increases the expression of Runt-related transcription factor 2 (RUNX2).	[14]
Simvastatin	DM30SGU	Approved	Simvastatin increases the expression of Runt-related transcription factor 2 (RUNX2).	[20]
Clodronate	DM9Y6X7	Approved	Clodronate increases the expression of Runt-related transcription factor 2 (RUNX2).	[14]
Vitamin C	DMXJ7O8	Approved	Vitamin C increases the expression of Runt-related transcription factor 2 (RUNX2).	[21]
Melatonin	DMKWFBT	Approved	Melatonin increases the expression of Runt-related transcription factor 2 (RUNX2).	[22]
Glucosamine	DM4ZLFD	Approved	Glucosamine increases the expression of Runt-related transcription factor 2 (RUNX2).	[23]
Ximelegatran	DMU8ANS	Approved	Ximelegatran decreases the expression of Runt-related transcription factor 2 (RUNX2).	[24]
Calcidiol	DMN4CV5	Approved	Calcidiol increases the expression of Runt-related transcription factor 2 (RUNX2).	[25]
Berberine	DMC5Q8X	Phase 4	Berberine increases the expression of Runt-related transcription factor 2 (RUNX2).	[26]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Runt-related transcription factor 2 (RUNX2).	[27]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene decreases the expression of Runt-related transcription factor 2 (RUNX2).	[4]
Curcumin	DMQPH29	Phase 3	Curcumin decreases the expression of Runt-related transcription factor 2 (RUNX2).	[28]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate increases the expression of Runt-related transcription factor 2 (RUNX2).	[29]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Runt-related transcription factor 2 (RUNX2).	[31]
GSK2816126	DMJDVW4	Phase 1	GSK2816126 increases the expression of Runt-related transcription factor 2 (RUNX2).	[32]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Runt-related transcription factor 2 (RUNX2).	[33]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Runt-related transcription factor 2 (RUNX2).	[34]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Runt-related transcription factor 2 (RUNX2).	[35]
D-glucose	DMMG2TO	Investigative	D-glucose decreases the expression of Runt-related transcription factor 2 (RUNX2).	[36]
CH-223191	DMMJZYC	Investigative	CH-223191 decreases the expression of Runt-related transcription factor 2 (RUNX2).	[37]
U0126	DM31OGF	Investigative	U0126 decreases the expression of Runt-related transcription factor 2 (RUNX2).	[38]
PD98059	DMZC90M	Investigative	PD98059 decreases the expression of Runt-related transcription factor 2 (RUNX2).	[27]
Benzoquinone	DMNBA0G	Investigative	Benzoquinone increases the expression of Runt-related transcription factor 2 (RUNX2).	[17]
Naringin	DM4DG1Y	Investigative	Naringin increases the expression of Runt-related transcription factor 2 (RUNX2).	[39]
Alpha-ketoglutaric acid	DM5LFYN	Investigative	Alpha-ketoglutaric acid increases the expression of Runt-related transcription factor 2 (RUNX2).	[40]

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