Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTH9DKAD)

• DOT Name: Homeobox protein Meis1 (MEIS1)
• Gene Name: MEIS1
• Related Disease:
  T-cell acute lymphoblastic leukaemia
  Acute leukaemia
  Acute monocytic leukemia
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Cardiovascular disease
  Childhood acute lymphoblastic leukemia
  Childhood myelodysplastic syndrome
  Colonic neoplasm
  Colorectal carcinoma
  Depression
  Epithelial neoplasm
  Ewing sarcoma
  Malignant peripheral nerve sheath tumor
  Matthew-Wood syndrome
  Medulloblastoma
  Melanoma
  Migraine disorder
  Myelodysplastic syndrome
  Neoplasm
  Neuroblastoma
  Promyelocytic leukaemia
  Prostate neoplasm
  Sleep disorder
  Sleep disorder, initiating and maintaining sleep
  Tourette syndrome
  Wilms tumor
  Chronic renal failure
  End-stage renal disease
  Endometriosis
  Myeloid leukaemia
  Chromosomal disorder
  Pneumonia
  Acute lymphocytic leukaemia
  Acute myelogenous leukaemia
  Acute undifferentiated leukemia
  Advanced cancer
  Cardiomyopathy
  Meningioma
  Microphthalmia
  Myeloproliferative neoplasm
  Prostate cancer
  Prostate carcinoma
• UniProt ID: MEIS1_HUMAN
• PDB ID: 4XRS; 5EGO
• Pfam ID: PF05920 ; PF16493
• Sequence:
  MAQRYDDLPHYGGMDGVGIPSTMYGDPHAARSMQPVHHLNHGPPLHSHQYPHTAHTNAMA
  PSMGSSVNDALKRDKDAIYGHPLFPLLALIFEKCELATCTPREPGVAGGDVCSSESFNED
  IAVFAKQIRAEKPLFSSNPELDNLMIQAIQVLRFHLLELEKVHELCDNFCHRYISCLKGK
  MPIDLVIDDREGGSKSDSEDITRSANLTDQPSWNRDHDDTASTRSGGTPGPSSGGHTSHS
  GDNSSEQGDGLDNSVASPSTGDDDDPDKDKKRHKKRGIFPKVATNIMRAWLFQHLTHPYP
  SEEQKKQLAQDTGLTILQVNNWFINARRRIVQPMIDQSNRAVSQGTPYNPDGQPMGGFVM
  DGQQHMGIRAPGPMSGMGMNMGMEGQWHYM
• Function: Acts as a transcriptional regulator of PAX6. Acts as a transcriptional activator of PF4 in complex with PBX1 or PBX2. Required for hematopoiesis, megakaryocyte lineage development and vascular patterning. May function as a cofactor for HOXA7 and HOXA9 in the induction of myeloid leukemias.
• Tissue Specificity: Expressed at low level in normal immunohepatopoietic tissues, including the fetal liver. Expressed in a subset of myeloid leukemia cell lines, with the highest expression seen in those with a megakaryocytic-erythroid phenotype. Also expressed at high levels in the cerebellum.
• KEGG Pathway:
  Sig.ling pathways regulating pluripotency of stem cells (hsa04550)
  Transcriptio.l misregulation in cancer (hsa05202)
• Reactome Pathway: Activation of anterior HOX genes in hindbrain development during early embryogenesis (R-HSA-5617472)

Molecular Interaction Atlas (MIA) of This DOT

44 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
T-cell acute lymphoblastic leukaemia	DIS17AI2	Definitive	Altered Expression	[1]
Acute leukaemia	DISDQFDI	Strong	Biomarker	[2]
Acute monocytic leukemia	DIS28NEL	Strong	Biomarker	[3]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[4]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[4]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[4]
Cardiovascular disease	DIS2IQDX	Strong	Genetic Variation	[5]
Childhood acute lymphoblastic leukemia	DISJ5D6U	Strong	Altered Expression	[6]
Childhood myelodysplastic syndrome	DISMN80I	Strong	Altered Expression	[7]
Colonic neoplasm	DISSZ04P	Strong	Genetic Variation	[8]
Colorectal carcinoma	DIS5PYL0	Strong	Altered Expression	[8]
Depression	DIS3XJ69	Strong	Genetic Variation	[9]
Epithelial neoplasm	DIS0T594	Strong	Posttranslational Modification	[8]
Ewing sarcoma	DISQYLV3	Strong	Altered Expression	[10]
Malignant peripheral nerve sheath tumor	DIS0JTN6	Strong	Biomarker	[11]
Matthew-Wood syndrome	DISA7HR7	Strong	Biomarker	[12]
Medulloblastoma	DISZD2ZL	Strong	Altered Expression	[13]
Melanoma	DIS1RRCY	Strong	Biomarker	[14]
Migraine disorder	DISFCQTG	Strong	Genetic Variation	[9]
Myelodysplastic syndrome	DISYHNUI	Strong	Altered Expression	[7]
Neoplasm	DISZKGEW	Strong	Biomarker	[15]
Neuroblastoma	DISVZBI4	Strong	Biomarker	[16]
Promyelocytic leukaemia	DISYGG13	Strong	Altered Expression	[17]
Prostate neoplasm	DISHDKGQ	Strong	Altered Expression	[15]
Sleep disorder	DIS3JP1U	Strong	Biomarker	[18]
Sleep disorder, initiating and maintaining sleep	DISVOIRA	Strong	Genetic Variation	[19]
Tourette syndrome	DISX9D54	Strong	Genetic Variation	[20]
Wilms tumor	DISB6T16	Strong	Altered Expression	[21]
Chronic renal failure	DISGG7K6	moderate	Genetic Variation	[22]
End-stage renal disease	DISXA7GG	moderate	Genetic Variation	[22]
Endometriosis	DISX1AG8	moderate	Genetic Variation	[23]
Myeloid leukaemia	DISMN944	moderate	Biomarker	[24]
Chromosomal disorder	DISM5BB5	Disputed	Altered Expression	[25]
Pneumonia	DIS8EF3M	Disputed	Biomarker	[26]
Acute lymphocytic leukaemia	DISPX75S	Limited	Altered Expression	[6]
Acute myelogenous leukaemia	DISCSPTN	Limited	Biomarker	[27]
Acute undifferentiated leukemia	DISJ4SSG	Limited	Biomarker	[28]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[29]
Cardiomyopathy	DISUPZRG	Limited	Biomarker	[30]
Meningioma	DISPT4TG	Limited	Biomarker	[31]
Microphthalmia	DISGEBES	Limited	Biomarker	[32]
Myeloproliferative neoplasm	DIS5KAPA	Limited	Altered Expression	[33]
Prostate cancer	DISF190Y	Limited	Biomarker	[34]
Prostate carcinoma	DISMJPLE	Limited	Biomarker	[34]

3 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 Homeobox protein Meis1 (MEIS1).	[35]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Homeobox protein Meis1 (MEIS1).	[41]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the methylation of Homeobox protein Meis1 (MEIS1).	[51]

21 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 Homeobox protein Meis1 (MEIS1).	[36]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Homeobox protein Meis1 (MEIS1).	[37]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Homeobox protein Meis1 (MEIS1).	[38]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Homeobox protein Meis1 (MEIS1).	[39]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Homeobox protein Meis1 (MEIS1).	[40]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Homeobox protein Meis1 (MEIS1).	[42]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Homeobox protein Meis1 (MEIS1).	[43]
Cytarabine	DMZD5QR	Approved	Cytarabine increases the expression of Homeobox protein Meis1 (MEIS1).	[44]
Malathion	DMXZ84M	Approved	Malathion decreases the expression of Homeobox protein Meis1 (MEIS1).	[45]
Alitretinoin	DMME8LH	Approved	Alitretinoin increases the expression of Homeobox protein Meis1 (MEIS1).	[37]
Vitamin A	DMJ2AH4	Approved	Vitamin A increases the expression of Homeobox protein Meis1 (MEIS1).	[37]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Homeobox protein Meis1 (MEIS1).	[46]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Homeobox protein Meis1 (MEIS1).	[47]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Homeobox protein Meis1 (MEIS1).	[48]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Homeobox protein Meis1 (MEIS1).	[49]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Homeobox protein Meis1 (MEIS1).	[50]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Homeobox protein Meis1 (MEIS1).	[52]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Homeobox protein Meis1 (MEIS1).	[53]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Homeobox protein Meis1 (MEIS1).	[54]
all-trans-4-oxo-retinoic acid	DMM2R1N	Investigative	all-trans-4-oxo-retinoic acid increases the expression of Homeobox protein Meis1 (MEIS1).	[37]
EPZ-004777	DMLN4V5	Investigative	EPZ-004777 decreases the expression of Homeobox protein Meis1 (MEIS1).	[55]

References

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