Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTSGJ8SV)

• DOT Name: Probable global transcription activator SNF2L2 (SMARCA2)
• Synonyms: EC 3.6.4.-; ATP-dependent helicase SMARCA2; BRG1-associated factor 190B; BAF190B; Protein brahma homolog; hBRM; SNF2-alpha; SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 2
• Gene Name: SMARCA2
• Related Disease:
  Acute myelogenous leukaemia
  Coffin-Siris syndrome 1
  Intellectual disability-sparse hair-brachydactyly syndrome
  Small-cell lung cancer
  Adult glioblastoma
  Astrocytoma
  Autism
  Breast neoplasm
  Carcinoma of esophagus
  Coffin-Siris syndrome
  Endometrial carcinoma
  Esophageal cancer
  Esophageal squamous cell carcinoma
  Gastric cancer
  Glioblastoma multiforme
  Glioma
  Head and neck cancer
  Head and neck carcinoma
  Head-neck squamous cell carcinoma
  Hepatitis C virus infection
  Intellectual disability
  Liver cirrhosis
  Lung neoplasm
  Malignant mesothelioma
  Neoplasm
  Neoplasm of esophagus
  Neurodevelopmental disorder
  Obesity
  Prostate cancer
  Prostate neoplasm
  Schimke immuno-osseous dysplasia
  Skin cancer
  Squamous cell carcinoma
  leukaemia
  Leukemia
  Lung adenocarcinoma
  Movement disorder
  Non-small-cell lung cancer
  Alpha thalassemia-X-linked intellectual disability syndrome
  Aplasia cutis congenita
  Autism spectrum disorder
  Carcinoma
  Chronic renal failure
  Clear cell renal carcinoma
  Corpus callosum, agenesis of
  End-stage renal disease
  Lung cancer
  Lung carcinoma
  Melanoma
  Pancreatic cancer
• UniProt ID: SMCA2_HUMAN
• PDB ID: 2DAT; 4QY4; 5DKC; 5DKH; 6EG2; 6EG3; 6HAX; 6HAY; 6HAZ; 7S4E; 7Z6L; 7Z76; 7Z77; 7Z78
• EC Number: 3.6.4.-
• Pfam ID: PF07533 ; PF00439 ; PF00271 ; PF07529 ; PF08880 ; PF14619 ; PF00176
• Sequence:
  MSTPTDPGAMPHPGPSPGPGPSPGPILGPSPGPGPSPGSVHSMMGPSPGPPSVSHPMPTM
  GSTDFPQEGMHQMHKPIDGIHDKGIVEDIHCGSMKGTGMRPPHPGMGPPQSPMDQHSQGY
  MSPHPSPLGAPEHVSSPMSGGGPTPPQMPPSQPGALIPGDPQAMSQPNRGPSPFSPVQLH
  QLRAQILAYKMLARGQPLPETLQLAVQGKRTLPGLQQQQQQQQQQQQQQQQQQQQQQQPQ
  QQPPQPQTQQQQQPALVNYNRPSGPGPELSGPSTPQKLPVPAPGGRPSPAPPAAAQPPAA
  AVPGPSVPQPAPGQPSPVLQLQQKQSRISPIQKPQGLDPVEILQEREYRLQARIAHRIQE
  LENLPGSLPPDLRTKATVELKALRLLNFQRQLRQEVVACMRRDTTLETALNSKAYKRSKR
  QTLREARMTEKLEKQQKIEQERKRRQKHQEYLNSILQHAKDFKEYHRSVAGKIQKLSKAV
  ATWHANTEREQKKETERIEKERMRRLMAEDEEGYRKLIDQKKDRRLAYLLQQTDEYVANL
  TNLVWEHKQAQAAKEKKKRRRRKKKAEENAEGGESALGPDGEPIDESSQMSDLPVKVTHT
  ETGKVLFGPEAPKASQLDAWLEMNPGYEVAPRSDSEESDSDYEEEDEEEESSRQETEEKI
  LLDPNSEEVSEKDAKQIIETAKQDVDDEYSMQYSARGSQSYYTVAHAISERVEKQSALLI
  NGTLKHYQLQGLEWMVSLYNNNLNGILADEMGLGKTIQTIALITYLMEHKRLNGPYLIIV
  PLSTLSNWTYEFDKWAPSVVKISYKGTPAMRRSLVPQLRSGKFNVLLTTYEYIIKDKHIL
  AKIRWKYMIVDEGHRMKNHHCKLTQVLNTHYVAPRRILLTGTPLQNKLPELWALLNFLLP
  TIFKSCSTFEQWFNAPFAMTGERVDLNEEETILIIRRLHKVLRPFLLRRLKKEVESQLPE
  KVEYVIKCDMSALQKILYRHMQAKGILLTDGSEKDKKGKGGAKTLMNTIMQLRKICNHPY
  MFQHIEESFAEHLGYSNGVINGAELYRASGKFELLDRILPKLRATNHRVLLFCQMTSLMT
  IMEDYFAFRNFLYLRLDGTTKSEDRAALLKKFNEPGSQYFIFLLSTRAGGLGLNLQAADT
  VVIFDSDWNPHQDLQAQDRAHRIGQQNEVRVLRLCTVNSVEEKILAAAKYKLNVDQKVIQ
  AGMFDQKSSSHERRAFLQAILEHEEENEEEDEVPDDETLNQMIARREEEFDLFMRMDMDR
  RREDARNPKRKPRLMEEDELPSWIIKDDAEVERLTCEEEEEKIFGRGSRQRRDVDYSDAL
  TEKQWLRAIEDGNLEEMEEEVRLKKRKRRRNVDKDPAKEDVEKAKKRRGRPPAEKLSPNP
  PKLTKQMNAIIDTVINYKDRCNVEKVPSNSQLEIEGNSSGRQLSEVFIQLPSRKELPEYY
  ELIRKPVDFKKIKERIRNHKYRSLGDLEKDVMLLCHNAQTFNLEGSQIYEDSIVLQSVFK
  SARQKIAKEEESEDESNEEEEEEDEEESESEAKSVKVKIKLNKKDDKGRDKGKGKKRPNR
  GKAKPVVSDFDSDEEQDEREQSEGSGTDDE
• Function: Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology). Component of SWI/SNF chromatin remodeling complexes that carry out key enzymatic activities, changing chromatin structure by altering DNA-histone contacts within a nucleosome in an ATP-dependent manner. Binds DNA non-specifically. Belongs to the neural progenitors-specific chromatin remodeling complex (npBAF complex) and the neuron-specific chromatin remodeling complex (nBAF complex). During neural development a switch from a stem/progenitor to a postmitotic chromatin remodeling mechanism occurs as neurons exit the cell cycle and become committed to their adult state. The transition from proliferating neural stem/progenitor cells to postmitotic neurons requires a switch in subunit composition of the npBAF and nBAF complexes. As neural progenitors exit mitosis and differentiate into neurons, npBAF complexes which contain ACTL6A/BAF53A and PHF10/BAF45A, are exchanged for homologous alternative ACTL6B/BAF53B and DPF1/BAF45B or DPF3/BAF45C subunits in neuron-specific complexes (nBAF). The npBAF complex is essential for the self-renewal/proliferative capacity of the multipotent neural stem cells. The nBAF complex along with CREST plays a role regulating the activity of genes essential for dendrite growth.
• KEGG Pathway:
  ATP-dependent chromatin remodeling (hsa03082)
  Thermogenesis (hsa04714)
  Hepatocellular carcinoma (hsa05225)
• Reactome Pathway:
  RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known (R-HSA-8939243)
  RMTs methylate histone arginines (R-HSA-3214858)

Molecular Interaction Atlas (MIA) of This DOT

50 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	Definitive	Genetic Variation	[1]
Coffin-Siris syndrome 1	DIS95FRP	Definitive	Autosomal dominant	[2]
Intellectual disability-sparse hair-brachydactyly syndrome	DISEB2FS	Definitive	Autosomal dominant	[3]
Small-cell lung cancer	DISK3LZD	Definitive	Biomarker	[4]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[5]
Astrocytoma	DISL3V18	Strong	Biomarker	[5]
Autism	DISV4V1Z	Strong	Biomarker	[6]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[7]
Carcinoma of esophagus	DISS6G4D	Strong	Altered Expression	[8]
Coffin-Siris syndrome	DIS8L03H	Strong	Genetic Variation	[9]
Endometrial carcinoma	DISXR5CY	Strong	Genetic Variation	[10]
Esophageal cancer	DISGB2VN	Strong	Altered Expression	[8]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Altered Expression	[8]
Gastric cancer	DISXGOUK	Strong	Genetic Variation	[11]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[5]
Glioma	DIS5RPEH	Strong	Genetic Variation	[5]
Head and neck cancer	DISBPSQZ	Strong	Genetic Variation	[12]
Head and neck carcinoma	DISOU1DS	Strong	Genetic Variation	[12]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Genetic Variation	[13]
Hepatitis C virus infection	DISQ0M8R	Strong	Altered Expression	[14]
Intellectual disability	DISMBNXP	Strong	Biomarker	[15]
Liver cirrhosis	DIS4G1GX	Strong	Altered Expression	[14]
Lung neoplasm	DISVARNB	Strong	Biomarker	[16]
Malignant mesothelioma	DISTHJGH	Strong	Biomarker	[17]
Neoplasm	DISZKGEW	Strong	Biomarker	[18]
Neoplasm of esophagus	DISOLKAQ	Strong	Altered Expression	[8]
Neurodevelopmental disorder	DIS372XH	Strong	Genetic Variation	[19]
Obesity	DIS47Y1K	Strong	Biomarker	[20]
Prostate cancer	DISF190Y	Strong	Altered Expression	[21]
Prostate neoplasm	DISHDKGQ	Strong	Altered Expression	[21]
Schimke immuno-osseous dysplasia	DISGEL3Z	Strong	Genetic Variation	[22]
Skin cancer	DISTM18U	Strong	Altered Expression	[23]
Squamous cell carcinoma	DISQVIFL	Strong	Biomarker	[24]
leukaemia	DISS7D1V	moderate	Genetic Variation	[25]
Leukemia	DISNAKFL	moderate	Genetic Variation	[25]
Lung adenocarcinoma	DISD51WR	moderate	Altered Expression	[26]
Movement disorder	DISOJJ2D	moderate	CausalMutation	[27]
Non-small-cell lung cancer	DIS5Y6R9	moderate	Biomarker	[18]
Alpha thalassemia-X-linked intellectual disability syndrome	DISV7OEV	Limited	Biomarker	[15]
Aplasia cutis congenita	DISMDAYM	Limited	Biomarker	[28]
Autism spectrum disorder	DISXK8NV	Limited	Genetic Variation	[29]
Carcinoma	DISH9F1N	Limited	Genetic Variation	[10]
Chronic renal failure	DISGG7K6	Limited	Genetic Variation	[30]
Clear cell renal carcinoma	DISBXRFJ	Limited	Posttranslational Modification	[31]
Corpus callosum, agenesis of	DISO9P40	Limited	Biomarker	[28]
End-stage renal disease	DISXA7GG	Limited	Genetic Variation	[30]
Lung cancer	DISCM4YA	Limited	Biomarker	[32]
Lung carcinoma	DISTR26C	Limited	Biomarker	[32]
Melanoma	DIS1RRCY	Limited	Altered Expression	[33]
Pancreatic cancer	DISJC981	Limited	Biomarker	[34]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Probable global transcription activator SNF2L2 (SMARCA2).	[35]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Probable global transcription activator SNF2L2 (SMARCA2).	[36]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Probable global transcription activator SNF2L2 (SMARCA2).	[37]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Probable global transcription activator SNF2L2 (SMARCA2).	[38]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Probable global transcription activator SNF2L2 (SMARCA2).	[39]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Probable global transcription activator SNF2L2 (SMARCA2).	[40]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Probable global transcription activator SNF2L2 (SMARCA2).	[41]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Probable global transcription activator SNF2L2 (SMARCA2).	[42]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Probable global transcription activator SNF2L2 (SMARCA2).	[43]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Probable global transcription activator SNF2L2 (SMARCA2).	[44]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Probable global transcription activator SNF2L2 (SMARCA2).	[45]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Probable global transcription activator SNF2L2 (SMARCA2).	[44]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Probable global transcription activator SNF2L2 (SMARCA2).	[44]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Probable global transcription activator SNF2L2 (SMARCA2).	[46]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Probable global transcription activator SNF2L2 (SMARCA2).	[47]
Geldanamycin	DMS7TC5	Discontinued in Phase 2	Geldanamycin increases the expression of Probable global transcription activator SNF2L2 (SMARCA2).	[49]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Probable global transcription activator SNF2L2 (SMARCA2).	[50]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Probable global transcription activator SNF2L2 (SMARCA2).	[51]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Probable global transcription activator SNF2L2 (SMARCA2).	[52]
geraniol	DMS3CBD	Investigative	geraniol decreases the expression of Probable global transcription activator SNF2L2 (SMARCA2).	[53]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Probable global transcription activator SNF2L2 (SMARCA2).	[48]

References

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