Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT100T3P)

• DOT Name: Lamin-B1 (LMNB1)
• Gene Name: LMNB1
• Related Disease:
  Advanced cancer
  Alzheimer disease
  Amyloidosis
  Amyotrophic lateral sclerosis
  Arteriosclerosis
  Atherosclerosis
  B-cell lymphoma
  Breast neoplasm
  Cerebellar ataxia
  Colon cancer
  Colon carcinoma
  Dilated cardiomyopathy 1A
  Endometriosis
  Hepatocellular carcinoma
  Herpes simplex infection
  Intestinal disorder
  Large cell lymphoma
  Leukodystrophy
  Liver cirrhosis
  Lung adenocarcinoma
  Lung cancer
  Lung carcinoma
  Malignant neoplasm
  Microcephaly
  Microcephaly 26, primary, autosomal dominant
  Multiple sclerosis
  Muscular dystrophy
  Neural tube defect
  Osteoarthritis
  Pancreatic cancer
  Pelizeaus-Merzbacher spectrum disorder
  Progressive multifocal leukoencephalopathy
  Promyelocytic leukaemia
  Prostate cancer
  Prostate carcinoma
  Retinoblastoma
  Autonomic nervous system disorder
  Breast cancer
  Breast carcinoma
  Carcinoma of liver and intrahepatic biliary tract
  Dysautonomia
  Liver cancer
  Adult-onset autosomal dominant demyelinating leukodystrophy
  Autosomal dominant primary microcephaly
  Chronic obstructive pulmonary disease
  Clear cell renal carcinoma
  Follicular lymphoma
  Neoplasm
  Nervous system disease
  Small lymphocytic lymphoma
• UniProt ID: LMNB1_HUMAN
• PDB ID: 2KPW; 3JT0; 3TYY; 3UMN; 5BNW; 5VVX; 7DTG
• Pfam ID: PF00038 ; PF00932
• Sequence:
  MATATPVPPRMGSRAGGPTTPLSPTRLSRLQEKEELRELNDRLAVYIDKVRSLETENSAL
  QLQVTEREEVRGRELTGLKALYETELADARRALDDTARERAKLQIELGKCKAEHDQLLLN
  YAKKESDLNGAQIKLREYEAALNSKDAALATALGDKKSLEGDLEDLKDQIAQLEASLAAA
  KKQLADETLLKVDLENRCQSLTEDLEFRKSMYEEEINETRRKHETRLVEVDSGRQIEYEY
  KLAQALHEMREQHDAQVRLYKEELEQTYHAKLENARLSSEMNTSTVNSAREELMESRMRI
  ESLSSQLSNLQKESRACLERIQELEDLLAKEKDNSRRMLTDKEREMAEIRDQMQQQLNDY
  EQLLDVKLALDMEISAYRKLLEGEEERLKLSPSPSSRVTVSRASSSRSVRTTRGKRKRVD
  VEESEASSSVSISHSASATGNVCIEEIDVDGKFIRLKNTSEQDQPMGGWEMIRKIGDTSV
  SYKYTSRYVLKAGQTVTIWAANAGVTASPPTDLIWKNQNSWGTGEDVKVILKNSQGEEVA
  QRSTVFKTTIPEEEEEEEEAAGVVVEEELFHQQGTPRASNRSCAIM
• Function: Lamins are intermediate filament proteins that assemble into a filamentous meshwork, and which constitute the major components of the nuclear lamina, a fibrous layer on the nucleoplasmic side of the inner nuclear membrane. Lamins provide a framework for the nuclear envelope, bridging the nuclear envelope and chromatin, thereby playing an important role in nuclear assembly, chromatin organization, nuclear membrane and telomere dynamics. The structural integrity of the lamina is strictly controlled by the cell cycle, as seen by the disintegration and formation of the nuclear envelope in prophase and telophase, respectively.
• KEGG Pathway:
  Apoptosis (hsa04210)
  Cytoskeleton in muscle cells (hsa04820)
• Reactome Pathway:
  Formation of Senescence-Associated Heterochromatin Foci (SAHF) (R-HSA-2559584)
  Nuclear Envelope Breakdown (R-HSA-2980766)
  Initiation of Nuclear Envelope (NE) Reformation (R-HSA-2995383)
  Breakdown of the nuclear lamina (R-HSA-352238)
  Depolymerization of the Nuclear Lamina (R-HSA-4419969)
  Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models (R-HSA-8862803)
  Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation (R-HSA-8950505)
  RHOD GTPase cycle (R-HSA-9013405)
  RHOF GTPase cycle (R-HSA-9035034)
  Meiotic synapsis (R-HSA-1221632)

Molecular Interaction Atlas (MIA) of This DOT

50 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Alzheimer disease	DISF8S70	Strong	Biomarker	[2]
Amyloidosis	DISHTAI2	Strong	Biomarker	[3]
Amyotrophic lateral sclerosis	DISF7HVM	Strong	Biomarker	[4]
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[5]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[5]
B-cell lymphoma	DISIH1YQ	Strong	Biomarker	[6]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[7]
Cerebellar ataxia	DIS9IRAV	Strong	Genetic Variation	[8]
Colon cancer	DISVC52G	Strong	Altered Expression	[9]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[9]
Dilated cardiomyopathy 1A	DIS0RK9Z	Strong	Biomarker	[10]
Endometriosis	DISX1AG8	Strong	Biomarker	[11]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[12]
Herpes simplex infection	DISL1SAV	Strong	Biomarker	[13]
Intestinal disorder	DISGPMUQ	Strong	Biomarker	[14]
Large cell lymphoma	DISYZHCP	Strong	Biomarker	[6]
Leukodystrophy	DISVY1TT	Strong	Genetic Variation	[15]
Liver cirrhosis	DIS4G1GX	Strong	Biomarker	[12]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[16]
Lung cancer	DISCM4YA	Strong	Biomarker	[1]
Lung carcinoma	DISTR26C	Strong	Biomarker	[1]
Malignant neoplasm	DISS6SNG	Strong	Biomarker	[17]
Microcephaly	DIS2GRD8	Strong	Autosomal dominant	[18]
Microcephaly 26, primary, autosomal dominant	DIS01UEV	Strong	Autosomal dominant	[19]
Multiple sclerosis	DISB2WZI	Strong	Biomarker	[20]
Muscular dystrophy	DISJD6P7	Strong	Genetic Variation	[21]
Neural tube defect	DIS5J95E	Strong	Biomarker	[22]
Osteoarthritis	DIS05URM	Strong	Altered Expression	[23]
Pancreatic cancer	DISJC981	Strong	Biomarker	[24]
Pelizeaus-Merzbacher spectrum disorder	DIS1ODJO	Strong	Altered Expression	[25]
Progressive multifocal leukoencephalopathy	DISX02WS	Strong	Biomarker	[26]
Promyelocytic leukaemia	DISYGG13	Strong	Biomarker	[26]
Prostate cancer	DISF190Y	Strong	Biomarker	[27]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[27]
Retinoblastoma	DISVPNPB	Strong	Altered Expression	[17]
Autonomic nervous system disorder	DIS6JLTA	moderate	Genetic Variation	[28]
Breast cancer	DIS7DPX1	moderate	Biomarker	[29]
Breast carcinoma	DIS2UE88	moderate	Biomarker	[29]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	moderate	Biomarker	[30]
Dysautonomia	DISF4MT6	moderate	Genetic Variation	[28]
Liver cancer	DISDE4BI	moderate	Biomarker	[30]
Adult-onset autosomal dominant demyelinating leukodystrophy	DIS5QR9B	Supportive	Autosomal dominant	[31]
Autosomal dominant primary microcephaly	DIS7WS7S	Supportive	Autosomal dominant	[19]
Chronic obstructive pulmonary disease	DISQCIRF	Limited	Altered Expression	[32]
Clear cell renal carcinoma	DISBXRFJ	Limited	Altered Expression	[33]
Follicular lymphoma	DISVEUR6	Limited	Altered Expression	[34]
Neoplasm	DISZKGEW	Limited	Biomarker	[1]
Nervous system disease	DISJ7GGT	Limited	Altered Expression	[35]
Small lymphocytic lymphoma	DIS30POX	Limited	Altered Expression	[34]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Vinblastine	DM5TVS3	Approved	Lamin-B1 (LMNB1) affects the response to substance of Vinblastine.	[81]

44 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 Lamin-B1 (LMNB1).	[36]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Lamin-B1 (LMNB1).	[37]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Lamin-B1 (LMNB1).	[38]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Lamin-B1 (LMNB1).	[39]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Lamin-B1 (LMNB1).	[40]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Lamin-B1 (LMNB1).	[41]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Lamin-B1 (LMNB1).	[42]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Lamin-B1 (LMNB1).	[43]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Lamin-B1 (LMNB1).	[44]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Lamin-B1 (LMNB1).	[45]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Lamin-B1 (LMNB1).	[46]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Lamin-B1 (LMNB1).	[47]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Lamin-B1 (LMNB1).	[48]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Lamin-B1 (LMNB1).	[49]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Lamin-B1 (LMNB1).	[48]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Lamin-B1 (LMNB1).	[50]
Decitabine	DMQL8XJ	Approved	Decitabine decreases the expression of Lamin-B1 (LMNB1).	[51]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Lamin-B1 (LMNB1).	[52]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Lamin-B1 (LMNB1).	[53]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Lamin-B1 (LMNB1).	[54]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Lamin-B1 (LMNB1).	[55]
Isotretinoin	DM4QTBN	Approved	Isotretinoin increases the expression of Lamin-B1 (LMNB1).	[56]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Lamin-B1 (LMNB1).	[57]
Dasatinib	DMJV2EK	Approved	Dasatinib decreases the expression of Lamin-B1 (LMNB1).	[58]
Menthol	DMG2KW7	Approved	Menthol increases the expression of Lamin-B1 (LMNB1).	[59]
Palbociclib	DMD7L94	Approved	Palbociclib decreases the expression of Lamin-B1 (LMNB1).	[60]
Bicalutamide	DMZMSPF	Approved	Bicalutamide decreases the expression of Lamin-B1 (LMNB1).	[61]
Dactinomycin	DM2YGNW	Approved	Dactinomycin decreases the expression of Lamin-B1 (LMNB1).	[40]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Lamin-B1 (LMNB1).	[64]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Lamin-B1 (LMNB1).	[65]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene affects the expression of Lamin-B1 (LMNB1).	[38]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate decreases the expression of Lamin-B1 (LMNB1).	[67]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Lamin-B1 (LMNB1).	[69]
PEITC	DMOMN31	Phase 2	PEITC decreases the expression of Lamin-B1 (LMNB1).	[70]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Lamin-B1 (LMNB1).	[71]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Lamin-B1 (LMNB1).	[72]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Lamin-B1 (LMNB1).	[73]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Lamin-B1 (LMNB1).	[75]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the expression of Lamin-B1 (LMNB1).	[67]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Lamin-B1 (LMNB1).	[76]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Lamin-B1 (LMNB1).	[77]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Lamin-B1 (LMNB1).	[78]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Lamin-B1 (LMNB1).	[79]
Glyphosate	DM0AFY7	Investigative	Glyphosate decreases the expression of Lamin-B1 (LMNB1).	[80]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Lovastatin	DM9OZWQ	Approved	Lovastatin decreases the farnesylation of Lamin-B1 (LMNB1).	[62]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of Lamin-B1 (LMNB1).	[74]
Beta-ionone	DM6QV8A	Investigative	Beta-ionone decreases the farnesylation of Lamin-B1 (LMNB1).	[62]

3 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Cladribine	DM3JDRP	Approved	Cladribine increases the cleavage of Lamin-B1 (LMNB1).	[63]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the cleavage of Lamin-B1 (LMNB1).	[66]
Rigosertib	DMOSTXF	Phase 3	Rigosertib increases the cleavage of Lamin-B1 (LMNB1).	[68]

References

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