Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTAG24N1)

• DOT Name: Cyclin-dependent kinase 4 inhibitor B (CDKN2B)
• Synonyms: Multiple tumor suppressor 2; MTS-2; p14-INK4b; p15-INK4b; p15INK4B
• Gene Name: CDKN2B
• Related Disease:
  Atherosclerosis
  Bladder cancer
  Breast cancer
  Breast carcinoma
  Carcinoma of esophagus
  Colorectal carcinoma
  Coronary atherosclerosis
  Coronary heart disease
  Epithelial ovarian cancer
  Gastric cancer
  Hepatocellular carcinoma
  Lung adenocarcinoma
  Lung carcinoma
  Multiple endocrine neoplasia type 1
  Non-small-cell lung cancer
  Ovarian neoplasm
  Pancreatic tumour
  Stomach cancer
  T-cell acute lymphoblastic leukaemia
  Urinary bladder cancer
  Urinary bladder neoplasm
  Acute leukaemia
  Childhood myelodysplastic syndrome
  Lymphoma
  Renal cell carcinoma
  Small lymphocytic lymphoma
  Adult T-cell leukemia/lymphoma
  Insulinoma
  Acute monocytic leukemia
  Astrocytoma
  Breast neoplasm
  Carcinoma
  Cardiovascular disease
  Chromosomal disorder
  Endometrial cancer
  Endometrium neoplasm
  Esophageal squamous cell carcinoma
  Glaucoma/ocular hypertension
  Lung cancer
  Malignant glioma
  Mixed glioma
  Multiple endocrine neoplasia
  Obsolete glaucoma 1, open angle, E
  Open-angle glaucoma
  Pancreatic cancer
  Retinoblastoma
  Squamous cell carcinoma
• UniProt ID: CDN2B_HUMAN
• Pfam ID: PF12796
• Sequence:
  MREENKGMPSGGGSDEGLASAAARGLVEKVRQLLEAGADPNGVNRFGRRAIQVMMMGSAR
  VAELLLLHGAEPNCADPATLTRPVHDAAREGFLDTLVVLHRAGARLDVRDAWGRLPVDLA
  EERGHRDVAGYLRTATGD
• Function: Interacts strongly with CDK4 and CDK6. Potent inhibitor. Potential effector of TGF-beta induced cell cycle arrest.
• Tissue Specificity: Isoform 2 is expressed in normal (keratinocytes, fibroblasts) and tumor cell lines.
• KEGG Pathway:
  FoxO sig.ling pathway (hsa04068)
  Cell cycle (hsa04110)
  Cellular senescence (hsa04218)
  TGF-beta sig.ling pathway (hsa04350)
  Cushing syndrome (hsa04934)
  Human T-cell leukemia virus 1 infection (hsa05166)
  Pathways in cancer (hsa05200)
  Viral carcinogenesis (hsa05203)
  Small cell lung cancer (hsa05222)
  Gastric cancer (hsa05226)
• Reactome Pathway:
  Oxidative Stress Induced Senescence (R-HSA-2559580)
  Senescence-Associated Secretory Phenotype (SASP) (R-HSA-2559582)
  Oncogene Induced Senescence (R-HSA-2559585)
  Cyclin D associated events in G1 (R-HSA-69231)
  SMAD2/SMAD3 (R-HSA-2173796)

Molecular Interaction Atlas (MIA) of This DOT

47 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Atherosclerosis	DISMN9J3	Definitive	Biomarker	[1]
Bladder cancer	DISUHNM0	Definitive	Altered Expression	[2]
Breast cancer	DIS7DPX1	Strong	Posttranslational Modification	[3]
Breast carcinoma	DIS2UE88	Strong	Posttranslational Modification	[3]
Carcinoma of esophagus	DISS6G4D	Strong	Altered Expression	[4]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[5]
Coronary atherosclerosis	DISKNDYU	Strong	Genetic Variation	[6]
Coronary heart disease	DIS5OIP1	Strong	Genetic Variation	[6]
Epithelial ovarian cancer	DIS56MH2	Strong	Altered Expression	[7]
Gastric cancer	DISXGOUK	Strong	Biomarker	[8]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[9]
Lung adenocarcinoma	DISD51WR	Strong	Genetic Variation	[10]
Lung carcinoma	DISTR26C	Strong	Biomarker	[11]
Multiple endocrine neoplasia type 1	DIS0RJRK	Strong	Biomarker	[12]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Posttranslational Modification	[13]
Ovarian neoplasm	DISEAFTY	Strong	Posttranslational Modification	[14]
Pancreatic tumour	DIS3U0LK	Strong	Biomarker	[15]
Stomach cancer	DISKIJSX	Strong	Biomarker	[8]
T-cell acute lymphoblastic leukaemia	DIS17AI2	Strong	Genetic Variation	[16]
Urinary bladder cancer	DISDV4T7	Strong	Altered Expression	[2]
Urinary bladder neoplasm	DIS7HACE	Strong	Altered Expression	[2]
Acute leukaemia	DISDQFDI	moderate	Biomarker	[17]
Childhood myelodysplastic syndrome	DISMN80I	moderate	Biomarker	[18]
Lymphoma	DISN6V4S	moderate	Genetic Variation	[19]
Renal cell carcinoma	DISQZ2X8	Moderate	Autosomal dominant	[20]
Small lymphocytic lymphoma	DIS30POX	moderate	Biomarker	[21]
Adult T-cell leukemia/lymphoma	DIS882XU	Disputed	Biomarker	[22]
Insulinoma	DISIU1JS	Disputed	Posttranslational Modification	[23]
Acute monocytic leukemia	DIS28NEL	Limited	Biomarker	[24]
Astrocytoma	DISL3V18	Limited	Genetic Variation	[25]
Breast neoplasm	DISNGJLM	Limited	Biomarker	[26]
Carcinoma	DISH9F1N	Limited	Genetic Variation	[27]
Cardiovascular disease	DIS2IQDX	Limited	Genetic Variation	[28]
Chromosomal disorder	DISM5BB5	Limited	Posttranslational Modification	[24]
Endometrial cancer	DISW0LMR	Limited	Biomarker	[29]
Endometrium neoplasm	DIS6OS2L	Limited	Biomarker	[29]
Esophageal squamous cell carcinoma	DIS5N2GV	Limited	Genetic Variation	[30]
Glaucoma/ocular hypertension	DISLBXBY	Limited	Genetic Variation	[31]
Lung cancer	DISCM4YA	Limited	Biomarker	[11]
Malignant glioma	DISFXKOV	Limited	Biomarker	[32]
Mixed glioma	DIS64UY3	Limited	Biomarker	[33]
Multiple endocrine neoplasia	DISZGBKW	Limited	Autosomal dominant	[34]
Obsolete glaucoma 1, open angle, E	DISL7Q3J	Limited	Autosomal dominant	[34]
Open-angle glaucoma	DISSZEE8	Limited	Genetic Variation	[35]
Pancreatic cancer	DISJC981	Limited	Genetic Variation	[36]
Retinoblastoma	DISVPNPB	Limited	Altered Expression	[37]
Squamous cell carcinoma	DISQVIFL	Limited	Genetic Variation	[38]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Palbociclib	DMD7L94	Approved	Cyclin-dependent kinase 4 inhibitor B (CDKN2B) decreases the response to substance of Palbociclib.	[80]

42 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 Cyclin-dependent kinase 4 inhibitor B (CDKN2B).	[39]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Cyclin-dependent kinase 4 inhibitor B (CDKN2B).	[40]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Cyclin-dependent kinase 4 inhibitor B (CDKN2B).	[41]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Cyclin-dependent kinase 4 inhibitor B (CDKN2B).	[42]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Cyclin-dependent kinase 4 inhibitor B (CDKN2B).	[43]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Cyclin-dependent kinase 4 inhibitor B (CDKN2B).	[44]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of Cyclin-dependent kinase 4 inhibitor B (CDKN2B).	[45]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Cyclin-dependent kinase 4 inhibitor B (CDKN2B).	[40]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Cyclin-dependent kinase 4 inhibitor B (CDKN2B).	[47]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Cyclin-dependent kinase 4 inhibitor B (CDKN2B).	[48]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Cyclin-dependent kinase 4 inhibitor B (CDKN2B).	[39]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Cyclin-dependent kinase 4 inhibitor B (CDKN2B).	[48]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Cyclin-dependent kinase 4 inhibitor B (CDKN2B).	[49]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Cyclin-dependent kinase 4 inhibitor B (CDKN2B).	[50]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Cyclin-dependent kinase 4 inhibitor B (CDKN2B).	[52]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Cyclin-dependent kinase 4 inhibitor B (CDKN2B).	[53]
Azathioprine	DMMZSXQ	Approved	Azathioprine increases the expression of Cyclin-dependent kinase 4 inhibitor B (CDKN2B).	[54]
Daunorubicin	DMQUSBT	Approved	Daunorubicin increases the expression of Cyclin-dependent kinase 4 inhibitor B (CDKN2B).	[56]
Gefitinib	DM15F0X	Approved	Gefitinib increases the expression of Cyclin-dependent kinase 4 inhibitor B (CDKN2B).	[57]
Ritonavir	DMU764S	Approved	Ritonavir increases the expression of Cyclin-dependent kinase 4 inhibitor B (CDKN2B).	[58]
Cantharidin	DMBP5N3	Approved	Cantharidin affects the expression of Cyclin-dependent kinase 4 inhibitor B (CDKN2B).	[59]
Prednisone	DM2HG4X	Approved	Prednisone increases the expression of Cyclin-dependent kinase 4 inhibitor B (CDKN2B).	[60]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Cyclin-dependent kinase 4 inhibitor B (CDKN2B).	[61]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Cyclin-dependent kinase 4 inhibitor B (CDKN2B).	[62]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Cyclin-dependent kinase 4 inhibitor B (CDKN2B).	[63]
I3C	DMIGFOR	Phase 3	I3C increases the expression of Cyclin-dependent kinase 4 inhibitor B (CDKN2B).	[64]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Cyclin-dependent kinase 4 inhibitor B (CDKN2B).	[65]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Cyclin-dependent kinase 4 inhibitor B (CDKN2B).	[66]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Cyclin-dependent kinase 4 inhibitor B (CDKN2B).	[67]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Cyclin-dependent kinase 4 inhibitor B (CDKN2B).	[68]
Harmine	DMPA5WD	Patented	Harmine decreases the expression of Cyclin-dependent kinase 4 inhibitor B (CDKN2B).	[69]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Cyclin-dependent kinase 4 inhibitor B (CDKN2B).	[70]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Cyclin-dependent kinase 4 inhibitor B (CDKN2B).	[71]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Cyclin-dependent kinase 4 inhibitor B (CDKN2B).	[72]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Cyclin-dependent kinase 4 inhibitor B (CDKN2B).	[73]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Cyclin-dependent kinase 4 inhibitor B (CDKN2B).	[74]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate decreases the expression of Cyclin-dependent kinase 4 inhibitor B (CDKN2B).	[75]
Phencyclidine	DMQBEYX	Investigative	Phencyclidine decreases the expression of Cyclin-dependent kinase 4 inhibitor B (CDKN2B).	[76]
Lithium chloride	DMHYLQ2	Investigative	Lithium chloride increases the expression of Cyclin-dependent kinase 4 inhibitor B (CDKN2B).	[77]
Linalool	DMGZQ5P	Investigative	Linalool increases the expression of Cyclin-dependent kinase 4 inhibitor B (CDKN2B).	[78]
PD98059	DMZC90M	Investigative	PD98059 increases the expression of Cyclin-dependent kinase 4 inhibitor B (CDKN2B).	[57]
GW-3965	DMG60ET	Investigative	GW-3965 increases the expression of Cyclin-dependent kinase 4 inhibitor B (CDKN2B).	[79]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the methylation of Cyclin-dependent kinase 4 inhibitor B (CDKN2B).	[46]
Decitabine	DMQL8XJ	Approved	Decitabine decreases the methylation of Cyclin-dependent kinase 4 inhibitor B (CDKN2B).	[51]
Azacitidine	DMTA5OE	Approved	Azacitidine decreases the methylation of Cyclin-dependent kinase 4 inhibitor B (CDKN2B).	[55]

References

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