Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTX931AW)

• DOT Name: Polycomb group protein ASXL1 (ASXL1)
• Synonyms: Additional sex combs-like protein 1
• Gene Name: ASXL1
• Related Disease:
  Acute myelogenous leukaemia
  Bohring-Opitz syndrome
  Myeloproliferative neoplasm
  Acute monocytic leukemia
  Aplastic anemia
  Blast phase chronic myelogenous leukemia, BCR-ABL1 positive
  Bone osteosarcoma
  Cardiac failure
  Childhood myelodysplastic syndrome
  Chronic myelomonocytic leukemia
  Congestive heart failure
  Dementia
  Depression
  Hematologic disease
  Inflammatory bowel disease
  Intellectual disability
  Late-onset Parkinson disease
  leukaemia
  Leukemia
  Lung cancer
  Lung carcinoma
  Mastocytosis
  Myelodysplastic/myeloproliferative neoplasm
  Myeloid neoplasm
  Neoplasm
  Osteosarcoma
  Parkinsonian disorder
  Promyelocytic leukaemia
  Systemic mastocytosis
  Wilms tumor
  Breast cancer
  Breast carcinoma
  Prostate cancer
  Prostate carcinoma
  Small lymphocytic lymphoma
  Myeloid leukaemia
  Anxiety
  Anxiety disorder
  Chronic myelomonocytic leukaemia
  Coronary heart disease
  Melanoma
  Movement disorder
  Non-hodgkin lymphoma
  Plasma cell myeloma
  Psychotic disorder
• UniProt ID: ASXL1_HUMAN
• PDB ID: 8H1T; 8SVF
• Pfam ID: PF13919 ; PF05066 ; PF13922
• Sequence:
  MKDKQKKKKERTWAEAARLVLENYSDAPMTPKQILQVIEAEGLKEMRSGTSPLACLNAML
  HSNSRGGEGLFYKLPGRISLFTLKKDALQWSRHPATVEGEEPEDTADVESCGSNEASTVS
  GENDVSLDETSSNASCSTESQSRPLSNPRDSYRASSQANKQKKKTGVMLPRVVLTPLKVN
  GAHVESASGFSGCHADGESGSPSSSSSGSLALGSAAIRGQAEVTQDPAPLLRGFRKPATG
  QMKRNRGEEIDFETPGSILVNTNLRALINSRTFHALPSHFQQQLLFLLPEVDRQVGTDGL
  LRLSSSALNNEFFTHAAQSWRERLADGEFTHEMQVRIRQEMEKEKKVEQWKEKFFEDYYG
  QKLGLTKEESLQQNVGQEEAEIKSGLCVPGESVRIQRGPATRQRDGHFKKRSRPDLRTRA
  RRNLYKKQESEQAGVAKDAKSVASDVPLYKDGEAKTDPAGLSSPHLPGTSSAAPDLEGPE
  FPVESVASRIQAEPDNLARASASPDRIPSLPQETVDQEPKDQKRKSFEQAASASFPEKKP
  RLEDRQSFRNTIESVHTEKPQPTKEEPKVPPIRIQLSRIKPPWVVKGQPTYQICPRIIPT
  TESSCRGWTGARTLADIKARALQVRGARGHHCHREAATTAIGGGGGPGGGGGGATDEGGG
  RGSSSGDGGEACGHPEPRGGPSTPGKCTSDLQRTQLLPPYPLNGEHTQAGTAMSRARRED
  LPSLRKEESCLLQRATVGLTDGLGDASQLPVAPTGDQPCQALPLLSSQTSVAERLVEQPQ
  LHPDVRTECESGTTSWESDDEEQGPTVPADNGPIPSLVGDDTLEKGTGQALDSHPTMKDP
  VNVTPSSTPESSPTDCLQNRAFDDELGLGGSCPPMRESDTRQENLKTKALVSNSSLHWIP
  IPSNDEVVKQPKPESREHIPSVEPQVGEEWEKAAPTPPALPGDLTAEEGLDPLDSLTSLW
  TVPSRGGSDSNGSYCQQVDIEKLKINGDSEALSPHGESTDTASDFEGHLTEDSSEADTRE
  AAVTKGSSVDKDEKPNWNQSAPLSKVNGDMRLVTRTDGMVAPQSWVSRVCAVRQKIPDSL
  LLASTEYQPRAVCLSMPGSSVEATNPLVMQLLQGSLPLEKVLPPAHDDSMSESPQVPLTK
  DQSHGSLRMGSLHGLGKNSGMVDGSSPSSLRALKEPLLPDSCETGTGLARIEATQAPGAP
  QKNCKAVPSFDSLHPVTNPITSSRKLEEMDSKEQFSSFSCEDQKEVRAMSQDSNSNAAPG
  KSPGDLTTSRTPRFSSPNVISFGPEQTGRALGDQSNVTGQGKKLFGSGNVAATLQRPRPA
  DPMPLPAEIPPVFPSGKLGPSTNSMSGGVQTPREDWAPKPHAFVGSVKNEKTFVGGPLKA
  NAENRKATGHSPLELVGHLEGMPFVMDLPFWKLPREPGKGLSEPLEPSSLPSQLSIKQAF
  YGKLSKLQLSSTSFNYSSSSPTFPKGLAGSVVQLSHKANFGASHSASLSLQMFTDSSTVE
  SISLQCACSLKAMIMCQGCGAFCHDDCIGPSKLCVLCLVVR
• Function: Probable Polycomb group (PcG) protein involved in transcriptional regulation mediated by ligand-bound nuclear hormone receptors, such as retinoic acid receptors (RARs) and peroxisome proliferator-activated receptor gamma (PPARG). Acts as a coactivator of RARA and RXRA through association with NCOA1. Acts as a corepressor for PPARG and suppresses its adipocyte differentiation-inducing activity. Non-catalytic component of the PR-DUB complex, a complex that specifically mediates deubiquitination of histone H2A monoubiquitinated at 'Lys-119' (H2AK119ub1). Acts as a sensor of N(6)-methyladenosine methylation on DNA (m6A): recognizes and binds m6A DNA, leading to its ubiquitination and degradation by TRIP12, thereby inactivating the PR-DUB complex and regulating Polycomb silencing.
• Tissue Specificity: Widely expressed at low level. Expressed in heart, brain, skeletal muscle, placenta, pancreas, spleen, prostate, small intestine, colon, peripheral blood, leukocytes, bone marrow and fetal liver. Highly expressed in testes.
• KEGG Pathway: Polycomb repressive complex (hsa03083)
• Reactome Pathway: UCH proteinases (R-HSA-5689603)

Molecular Interaction Atlas (MIA) of This DOT

45 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acute myelogenous leukaemia	DISCSPTN	Definitive	Genetic Variation	[1]
Bohring-Opitz syndrome	DIS1DZV4	Definitive	Autosomal dominant	[2]
Myeloproliferative neoplasm	DIS5KAPA	Definitive	Genetic Variation	[3]
Acute monocytic leukemia	DIS28NEL	Strong	Biomarker	[4]
Aplastic anemia	DISJRSC0	Strong	Biomarker	[5]
Blast phase chronic myelogenous leukemia, BCR-ABL1 positive	DIS3KLUX	Strong	Biomarker	[6]
Bone osteosarcoma	DIST1004	Strong	Biomarker	[7]
Cardiac failure	DISDC067	Strong	Biomarker	[8]
Childhood myelodysplastic syndrome	DISMN80I	Strong	Biomarker	[9]
Chronic myelomonocytic leukemia	DISIL8UR	Strong	Biomarker	[10]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[8]
Dementia	DISXL1WY	Strong	Genetic Variation	[11]
Depression	DIS3XJ69	Strong	Genetic Variation	[12]
Hematologic disease	DIS9XD9A	Strong	Genetic Variation	[13]
Inflammatory bowel disease	DISGN23E	Strong	Biomarker	[14]
Intellectual disability	DISMBNXP	Strong	Biomarker	[15]
Late-onset Parkinson disease	DIS9IOUI	Strong	Biomarker	[16]
leukaemia	DISS7D1V	Strong	Genetic Variation	[6]
Leukemia	DISNAKFL	Strong	Genetic Variation	[6]
Lung cancer	DISCM4YA	Strong	Genetic Variation	[17]
Lung carcinoma	DISTR26C	Strong	Genetic Variation	[17]
Mastocytosis	DIS1TEE0	Strong	Genetic Variation	[18]
Myelodysplastic/myeloproliferative neoplasm	DISDHXQ4	Strong	Genetic Variation	[19]
Myeloid neoplasm	DIS2YOWO	Strong	Biomarker	[20]
Neoplasm	DISZKGEW	Strong	Genetic Variation	[21]
Osteosarcoma	DISLQ7E2	Strong	Biomarker	[7]
Parkinsonian disorder	DISHGY45	Strong	Biomarker	[22]
Promyelocytic leukaemia	DISYGG13	Strong	Biomarker	[23]
Systemic mastocytosis	DISNQ2OY	Strong	Genetic Variation	[24]
Wilms tumor	DISB6T16	Strong	Biomarker	[25]
Breast cancer	DIS7DPX1	moderate	Genetic Variation	[26]
Breast carcinoma	DIS2UE88	moderate	Genetic Variation	[26]
Prostate cancer	DISF190Y	moderate	Genetic Variation	[26]
Prostate carcinoma	DISMJPLE	moderate	Genetic Variation	[26]
Small lymphocytic lymphoma	DIS30POX	moderate	Genetic Variation	[26]
Myeloid leukaemia	DISMN944	Disputed	Genetic Variation	[27]
Anxiety	DISIJDBA	Limited	Biomarker	[28]
Anxiety disorder	DISBI2BT	Limited	Biomarker	[28]
Chronic myelomonocytic leukaemia	DISDN5P7	Limited	Genetic Variation	[29]
Coronary heart disease	DIS5OIP1	Limited	Biomarker	[30]
Melanoma	DIS1RRCY	Limited	Biomarker	[31]
Movement disorder	DISOJJ2D	Limited	Biomarker	[32]
Non-hodgkin lymphoma	DISS2Y8A	Limited	Biomarker	[33]
Plasma cell myeloma	DIS0DFZ0	Limited	Genetic Variation	[34]
Psychotic disorder	DIS4UQOT	Limited	Genetic Variation	[35]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Polycomb group protein ASXL1 (ASXL1).	[36]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Polycomb group protein ASXL1 (ASXL1).	[37]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Polycomb group protein ASXL1 (ASXL1).	[38]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Polycomb group protein ASXL1 (ASXL1).	[39]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Polycomb group protein ASXL1 (ASXL1).	[40]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Polycomb group protein ASXL1 (ASXL1).	[41]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of Polycomb group protein ASXL1 (ASXL1).	[42]
Rigosertib	DMOSTXF	Phase 3	Rigosertib increases the expression of Polycomb group protein ASXL1 (ASXL1).	[43]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Polycomb group protein ASXL1 (ASXL1).	[40]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Polycomb group protein ASXL1 (ASXL1).	[47]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Polycomb group protein ASXL1 (ASXL1).	[41]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Polycomb group protein ASXL1 (ASXL1).	[48]
GALLICACID	DM6Y3A0	Investigative	GALLICACID decreases the expression of Polycomb group protein ASXL1 (ASXL1).	[49]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Polycomb group protein ASXL1 (ASXL1).	[44]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Polycomb group protein ASXL1 (ASXL1).	[45]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Polycomb group protein ASXL1 (ASXL1).	[46]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Polycomb group protein ASXL1 (ASXL1).	[46]

References

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