Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9799VN)

• DOT Name: SCL-interrupting locus protein (STIL)
• Synonyms: TAL-1-interrupting locus protein
• Gene Name: STIL
• Related Disease:
  Autosomal recessive primary microcephaly
  Hepatic encephalopathy
  Wilms tumor
  Acute leukaemia
  Acute undifferentiated leukemia
  Advanced cancer
  Anal intraepithelial neoplasia
  Cervical cancer
  Cervical carcinoma
  Cervical Intraepithelial neoplasia
  Epithelial ovarian cancer
  Human papillomavirus infection
  Leukemia
  Lissencephaly spectrum disorders
  Lymphoblastic lymphoma
  Lymphoma, non-Hodgkin, familial
  Microcephaly 6, primary, autosomal recessive
  Microcephaly 7, primary, autosomal recessive
  Neoplasm
  Non-hodgkin lymphoma
  Ovarian cancer
  Ovarian neoplasm
  Prostate cancer
  Prostate carcinoma
  Small lymphocytic lymphoma
  T-cell acute lymphoblastic leukaemia
  Carcinoma
  Intellectual disability
  Intrahepatic cholangiocarcinoma
  Isolated congenital microcephaly
  Lobar holoprosencephaly
  Methicillin-resistant staphylococci infection
  Pancreatic ductal carcinoma
  Patent ductus arteriosus
  Squamous cell carcinoma
  Vulvar squamous intraepithelial lesion
  Holoprosencephaly
  Acute lymphocytic leukaemia
  Childhood acute lymphoblastic leukemia
  Gastric cancer
  Stomach cancer
  Arrhythmia
  Disseminated intravascular coagulation
  leukaemia
  Nasopharyngeal carcinoma
• UniProt ID: STIL_HUMAN
• PDB ID: 4YYP; 5LHW; 5LHZ; 8OYK; 8OYL
• Pfam ID: PF15253
• Sequence:
  MEPIYPFARPQMNTRFPSSRMVPFHFPPSKCALWNPTPTGDFIYLHLSYYRNPKLVVTEK
  TIRLAYRHAKQNKKNSSCFLLGSLTADEDEEGVTLTVDRFDPGREVPECLEITPTASLPG
  DFLIPCKVHTQELCSREMIVHSVDDFSSALKALQCHICSKDSLDCGKLLSLRVHITSRES
  LDSVEFDLHWAAVTLANNFKCTPVKPIPIIPTALARNLSSNLNISQVQGTYKYGYLTMDE
  TRKLLLLLESDPKVYSLPLVGIWLSGITHIYSPQVWACCLRYIFNSSVQERVFSESGNFI
  IVLYSMTHKEPEFYECFPCDGKIPDFRFQLLTSKETLHLFKNVEPPDKNPIRCELSAESQ
  NAETEFFSKASKNFSIKRSSQKLSSGKMPIHDHDSGVEDEDFSPRPIPSPHPVSQKISKI
  QPSVPELSLVLDGNFIESNPLPTPLEMVNNENPPLINHLEHLKPLQPQLYDEKHSPEVEA
  GEPSLRGIPNQLNQDKPALLRHCKVRQPPAYKKGNPHTRNSIKPSSHNGPSHDIFEKLQT
  VSAGNVQNEEYPIRPSTLNSRQSSLAPQSQPHDFVFSPHNSGRPMELQIPTPPLPSYCST
  NVCRCCQHHSHIQYSPLNSWQGANTVGSIQDVQSEALQKHSLFHPSGCPALYCNAFCSSS
  SPIALRPQGDMGSCSPHSNIEPSPVARPPSHMDLCNPQPCTVCMHTPKTESDNGMMGLSP
  DAYRFLTEQDRQLRLLQAQIQRLLEAQSLMPCSPKTTAVEDTVQAGRQMELVSVEAQSSP
  GLHMRKGVSIAVSTGASLFWNAAGEDQEPDSQMKQDDTKISSEDMNFSVDINNEVTSLPG
  SASSLKAVDIPSFEESNIAVEEEFNQPLSVSNSSLVVRKEPDVPVFFPSGQLAESVSMCL
  QTGPTGGASNNSETSEEPKIEHVMQPLLHQPSDNQKIYQDLLGQVNHLLNSSSKETEQPS
  TKAVIISHECTRTQNVYHTKKKTHHSRLVDKDCVLNATLKQLRSLGVKIDSPTKVKKNAH
  NVDHASVLACISPEAVISGLNCMSFANVGMSGLSPNGVDLSMEANAIALKYLNENQLSQL
  SVTRSNQNNCDPFSLLHINTDRSTVGLSLISPNNMSFATKKYMKRYGLLQSSDNSEDEEE
  PPDNADSKSEYLLNQNLRSIPEQLGGQKEPSKNDHEIINCSNCESVGTNADTPVLRNITN
  EVLQTKAKQQLTEKPAFLVKNLKPSPAVNLRTGKAEFTQHPEKENEGDITIFPESLQPSE
  TLKQMNSMNSVGTFLDVKRLRQLPKLF
• Function: Immediate-early gene. Plays an important role in embryonic development as well as in cellular growth and proliferation; its long-term silencing affects cell survival and cell cycle distribution as well as decreases CDK1 activity correlated with reduced phosphorylation of CDK1. Plays a role as a positive regulator of the sonic hedgehog pathway, acting downstream of PTCH1. Plays an important role in the regulation of centriole duplication. Required for the onset of procentriole formation and proper mitotic progression. During procentriole formation, is essential for the correct loading of SASS6 and CENPJ to the base of the procentriole to initiate procentriole assembly. In complex with STIL acts as a modulator of PLK4-driven cytoskeletal rearrangements and directional cell motility.
• Tissue Specificity: Expressed in all hematopoietic tissues and cell lines. Highly expressed in a variety of tumors characterized by increased mitotic activity with highest expression in lung cancer.

Molecular Interaction Atlas (MIA) of This DOT

45 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autosomal recessive primary microcephaly	DIS29IE3	Definitive	Autosomal recessive	[1]
Hepatic encephalopathy	DISEAKAN	Definitive	Biomarker	[2]
Wilms tumor	DISB6T16	Definitive	Altered Expression	[3]
Acute leukaemia	DISDQFDI	Strong	Biomarker	[4]
Acute undifferentiated leukemia	DISJ4SSG	Strong	Genetic Variation	[5]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[6]
Anal intraepithelial neoplasia	DISJ0JW3	Strong	Biomarker	[7]
Cervical cancer	DISFSHPF	Strong	Biomarker	[8]
Cervical carcinoma	DIST4S00	Strong	Biomarker	[8]
Cervical Intraepithelial neoplasia	DISXP757	Strong	Biomarker	[9]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[10]
Human papillomavirus infection	DISX61LX	Strong	Biomarker	[11]
Leukemia	DISNAKFL	Strong	Biomarker	[12]
Lissencephaly spectrum disorders	DISBCZL7	Strong	Genetic Variation	[13]
Lymphoblastic lymphoma	DISB9ZYC	Strong	Genetic Variation	[14]
Lymphoma, non-Hodgkin, familial	DISCXYIZ	Strong	Biomarker	[15]
Microcephaly 6, primary, autosomal recessive	DISWFNUJ	Strong	Genetic Variation	[16]
Microcephaly 7, primary, autosomal recessive	DISY36JJ	Strong	Autosomal recessive	[17]
Neoplasm	DISZKGEW	Strong	Biomarker	[18]
Non-hodgkin lymphoma	DISS2Y8A	Strong	Biomarker	[15]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[10]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[10]
Prostate cancer	DISF190Y	Strong	Biomarker	[18]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[18]
Small lymphocytic lymphoma	DIS30POX	Strong	Biomarker	[15]
T-cell acute lymphoblastic leukaemia	DIS17AI2	Strong	Biomarker	[4]
Carcinoma	DISH9F1N	moderate	Biomarker	[11]
Intellectual disability	DISMBNXP	moderate	Genetic Variation	[19]
Intrahepatic cholangiocarcinoma	DIS6GOC8	moderate	Biomarker	[20]
Isolated congenital microcephaly	DISUXHZ6	moderate	Biomarker	[21]
Lobar holoprosencephaly	DISVK1YW	moderate	Genetic Variation	[22]
Methicillin-resistant staphylococci infection	DIS6DRDZ	moderate	Biomarker	[23]
Pancreatic ductal carcinoma	DIS26F9Q	moderate	Altered Expression	[24]
Patent ductus arteriosus	DIS9P8YS	moderate	Biomarker	[24]
Squamous cell carcinoma	DISQVIFL	moderate	Biomarker	[25]
Vulvar squamous intraepithelial lesion	DISULIZR	moderate	Biomarker	[11]
Holoprosencephaly	DISR35EC	Supportive	Autosomal recessive	[26]
Acute lymphocytic leukaemia	DISPX75S	Disputed	Genetic Variation	[27]
Childhood acute lymphoblastic leukemia	DISJ5D6U	Disputed	Genetic Variation	[27]
Gastric cancer	DISXGOUK	Disputed	Altered Expression	[28]
Stomach cancer	DISKIJSX	Disputed	Altered Expression	[28]
Arrhythmia	DISFF2NI	Limited	Biomarker	[29]
Disseminated intravascular coagulation	DISCAVOZ	Limited	Biomarker	[30]
leukaemia	DISS7D1V	Limited	Biomarker	[30]
Nasopharyngeal carcinoma	DISAOTQ0	Limited	Biomarker	[31]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of SCL-interrupting locus protein (STIL).	[32]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of SCL-interrupting locus protein (STIL).	[33]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of SCL-interrupting locus protein (STIL).	[34]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of SCL-interrupting locus protein (STIL).	[35]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of SCL-interrupting locus protein (STIL).	[36]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of SCL-interrupting locus protein (STIL).	[37]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of SCL-interrupting locus protein (STIL).	[37]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of SCL-interrupting locus protein (STIL).	[38]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of SCL-interrupting locus protein (STIL).	[39]
Dasatinib	DMJV2EK	Approved	Dasatinib decreases the expression of SCL-interrupting locus protein (STIL).	[40]
Palbociclib	DMD7L94	Approved	Palbociclib decreases the expression of SCL-interrupting locus protein (STIL).	[41]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of SCL-interrupting locus protein (STIL).	[42]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of SCL-interrupting locus protein (STIL).	[43]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of SCL-interrupting locus protein (STIL).	[44]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of SCL-interrupting locus protein (STIL).	[45]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of SCL-interrupting locus protein (STIL).	[46]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of SCL-interrupting locus protein (STIL).	[48]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of SCL-interrupting locus protein (STIL).	[35]
OXYQUINOLINE	DMZVS9Y	Investigative	OXYQUINOLINE decreases the expression of SCL-interrupting locus protein (STIL).	[36]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of SCL-interrupting locus protein (STIL).	[47]

References

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