Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTN0ZWAE)

DOT Name	Cyclin-dependent kinase inhibitor 2A (CDKN2A)
Synonyms	Cyclin-dependent kinase 4 inhibitor A; CDK4I; Multiple tumor suppressor 1; MTS-1; p16-INK4a; p16-INK4; p16INK4A
Gene Name	CDKN2A
Related Disease	Melanoma-pancreatic cancer syndrome ( ) Familial atypical multiple mole melanoma syndrome ( ) Melanoma and neural system tumor syndrome ( )
UniProt ID	CDN2A_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	1A5E; 1BI7; 1DC2; 2A5E; 7OZT
Sequence	MEPAAGSSMEPSADWLATAAARGRVEEVRALLEAGALPNAPNSYGRRPIQVMMMGSARVA ELLLLHGAEPNCADPATLTRPVHDAAREGFLDTLVVLHRAGARLDVRDAWGRLPVDLAEE LGHRDVARYLRAAAGGTRGSNHARIDAAEGPSDIPD
Function	Acts as a negative regulator of the proliferation of normal cells by interacting strongly with CDK4 and CDK6. This inhibits their ability to interact with cyclins D and to phosphorylate the retinoblastoma protein.
Tissue Specificity	Widely expressed but not detected in brain or skeletal muscle. Isoform 3 is pancreas-specific.
KEGG Pathway	Endocrine resistance (hsa01522 ) Platinum drug resistance (hsa01524 ) Cell cycle (hsa04110 ) p53 sig.ling pathway (hsa04115 ) Cellular senescence (hsa04218 ) Cushing syndrome (hsa04934 ) Human cytomegalovirus infection (hsa05163 ) Human T-cell leukemia virus 1 infection (hsa05166 ) Pathways in cancer (hsa05200 ) Viral carcinogenesis (hsa05203 ) MicroR.s in cancer (hsa05206 ) Pancreatic cancer (hsa05212 ) Glioma (hsa05214 ) Melanoma (hsa05218 ) Bladder cancer (hsa05219 ) Chronic myeloid leukemia (hsa05220 ) Non-small cell lung cancer (hsa05223 ) Hepatocellular carcinoma (hsa05225 )
Reactome Pathway	Senescence-Associated Secretory Phenotype (SASP) (R-HSA-2559582 ) Oncogene Induced Senescence (R-HSA-2559585 ) Cyclin D associated events in G1 (R-HSA-69231 ) Transcriptional Regulation by VENTX (R-HSA-8853884 ) Evasion of Oncogene Induced Senescence Due to Defective p16INK4A binding to CDK4 (R-HSA-9630791 ) Evasion of Oncogene Induced Senescence Due to Defective p16INK4A binding to CDK4 and CDK6 (R-HSA-9630794 ) Evasion of Oxidative Stress Induced Senescence Due to Defective p16INK4A binding to CDK4 (R-HSA-9632697 ) Evasion of Oxidative Stress Induced Senescence Due to Defective p16INK4A binding to CDK4 and CDK6 (R-HSA-9632700 ) Oxidative Stress Induced Senescence (R-HSA-2559580 )

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Melanoma-pancreatic cancer syndrome	DISFJV9Z	Definitive	Autosomal dominant	[1]
Familial atypical multiple mole melanoma syndrome	DIS2YEKP	Supportive	Autosomal dominant	[2]
Melanoma and neural system tumor syndrome	DISMA3X2	Limited	Autosomal dominant	[3]
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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

This DOT Affected the Drug Response of 3 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
DTI-015	DMXZRW0	Approved	Cyclin-dependent kinase inhibitor 2A (CDKN2A) increases the response to substance of DTI-015.	[63]
Palbociclib	DMD7L94	Approved	Cyclin-dependent kinase inhibitor 2A (CDKN2A) increases the response to substance of Palbociclib.	[64]
BMS-754807	DMPK32V	Phase 1	Cyclin-dependent kinase inhibitor 2A (CDKN2A) decreases the response to substance of BMS-754807.	[65]
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11 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 Cyclin-dependent kinase inhibitor 2A (CDKN2A).	[4]
Arsenic	DMTL2Y1	Approved	Arsenic increases the methylation of Cyclin-dependent kinase inhibitor 2A (CDKN2A).	[12]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the methylation of Cyclin-dependent kinase inhibitor 2A (CDKN2A).	[14]
Triclosan	DMZUR4N	Approved	Triclosan increases the methylation of Cyclin-dependent kinase inhibitor 2A (CDKN2A).	[16]
Decitabine	DMQL8XJ	Approved	Decitabine decreases the methylation of Cyclin-dependent kinase inhibitor 2A (CDKN2A).	[17]
Folic acid	DMEMBJC	Approved	Folic acid affects the methylation of Cyclin-dependent kinase inhibitor 2A (CDKN2A).	[21]
Azacitidine	DMTA5OE	Approved	Azacitidine decreases the methylation of Cyclin-dependent kinase inhibitor 2A (CDKN2A).	[27]
Hydralazine	DMU8JGH	Approved	Hydralazine decreases the methylation of Cyclin-dependent kinase inhibitor 2A (CDKN2A).	[36]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate decreases the methylation of Cyclin-dependent kinase inhibitor 2A (CDKN2A).	[39]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Cyclin-dependent kinase inhibitor 2A (CDKN2A).	[49]
Hydroxydimethylarsine Oxide	DMPS2B1	Investigative	Hydroxydimethylarsine Oxide decreases the methylation of Cyclin-dependent kinase inhibitor 2A (CDKN2A).	[60]
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⏷ Show the Full List of 11 Drug(s)

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Cyclin-dependent kinase inhibitor 2A (CDKN2A).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Cyclin-dependent kinase inhibitor 2A (CDKN2A).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Cyclin-dependent kinase inhibitor 2A (CDKN2A).	[7]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Cyclin-dependent kinase inhibitor 2A (CDKN2A).	[8]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Cyclin-dependent kinase inhibitor 2A (CDKN2A).	[9]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Cyclin-dependent kinase inhibitor 2A (CDKN2A).	[10]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Cyclin-dependent kinase inhibitor 2A (CDKN2A).	[11]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Cyclin-dependent kinase inhibitor 2A (CDKN2A).	[13]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Cyclin-dependent kinase inhibitor 2A (CDKN2A).	[15]
Marinol	DM70IK5	Approved	Marinol increases the expression of Cyclin-dependent kinase inhibitor 2A (CDKN2A).	[18]
Menadione	DMSJDTY	Approved	Menadione increases the expression of Cyclin-dependent kinase inhibitor 2A (CDKN2A).	[19]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Cyclin-dependent kinase inhibitor 2A (CDKN2A).	[20]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Cyclin-dependent kinase inhibitor 2A (CDKN2A).	[22]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of Cyclin-dependent kinase inhibitor 2A (CDKN2A).	[23]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of Cyclin-dependent kinase inhibitor 2A (CDKN2A).	[24]
Irinotecan	DMP6SC2	Approved	Irinotecan decreases the expression of Cyclin-dependent kinase inhibitor 2A (CDKN2A).	[25]
Menthol	DMG2KW7	Approved	Menthol increases the expression of Cyclin-dependent kinase inhibitor 2A (CDKN2A).	[26]
Zidovudine	DM4KI7O	Approved	Zidovudine increases the expression of Cyclin-dependent kinase inhibitor 2A (CDKN2A).	[9]
Capsaicin	DMGMF6V	Approved	Capsaicin increases the expression of Cyclin-dependent kinase inhibitor 2A (CDKN2A).	[28]
Daunorubicin	DMQUSBT	Approved	Daunorubicin affects the expression of Cyclin-dependent kinase inhibitor 2A (CDKN2A).	[29]
Hydroxyurea	DMOQVU9	Approved	Hydroxyurea increases the expression of Cyclin-dependent kinase inhibitor 2A (CDKN2A).	[30]
Docetaxel	DMDI269	Approved	Docetaxel decreases the expression of Cyclin-dependent kinase inhibitor 2A (CDKN2A).	[9]
Capecitabine	DMTS85L	Approved	Capecitabine decreases the expression of Cyclin-dependent kinase inhibitor 2A (CDKN2A).	[31]
Thioridazine	DM35M8J	Approved	Thioridazine increases the expression of Cyclin-dependent kinase inhibitor 2A (CDKN2A).	[32]
Masoprocol	DMMVNZ0	Approved	Masoprocol increases the expression of Cyclin-dependent kinase inhibitor 2A (CDKN2A).	[33]
Prednisone	DM2HG4X	Approved	Prednisone increases the expression of Cyclin-dependent kinase inhibitor 2A (CDKN2A).	[34]
Chloramphenicol	DMFXEWT	Approved	Chloramphenicol increases the expression of Cyclin-dependent kinase inhibitor 2A (CDKN2A).	[35]
Procainamide	DMNMXR8	Approved	Procainamide increases the expression of Cyclin-dependent kinase inhibitor 2A (CDKN2A).	[37]
Vinorelbine	DMVXFYE	Approved	Vinorelbine decreases the expression of Cyclin-dependent kinase inhibitor 2A (CDKN2A).	[31]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Cyclin-dependent kinase inhibitor 2A (CDKN2A).	[38]
Curcumin	DMQPH29	Phase 3	Curcumin decreases the expression of Cyclin-dependent kinase inhibitor 2A (CDKN2A).	[40]
Fenretinide	DMRD5SP	Phase 3	Fenretinide increases the expression of Cyclin-dependent kinase inhibitor 2A (CDKN2A).	[41]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of Cyclin-dependent kinase inhibitor 2A (CDKN2A).	[42]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the mutagenesis of Cyclin-dependent kinase inhibitor 2A (CDKN2A).	[43]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Cyclin-dependent kinase inhibitor 2A (CDKN2A).	[44]
Mivebresib	DMCPF90	Phase 1	Mivebresib increases the expression of Cyclin-dependent kinase inhibitor 2A (CDKN2A).	[45]
Harmine	DMPA5WD	Patented	Harmine decreases the expression of Cyclin-dependent kinase inhibitor 2A (CDKN2A).	[46]
Dioscin	DM5H2W9	Preclinical	Dioscin increases the expression of Cyclin-dependent kinase inhibitor 2A (CDKN2A).	[47]
Calphostin C	DM9X2D0	Terminated	Calphostin C affects the expression of Cyclin-dependent kinase inhibitor 2A (CDKN2A).	[48]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Cyclin-dependent kinase inhibitor 2A (CDKN2A).	[42]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of Cyclin-dependent kinase inhibitor 2A (CDKN2A).	[50]
Glyphosate	DM0AFY7	Investigative	Glyphosate decreases the expression of Cyclin-dependent kinase inhibitor 2A (CDKN2A).	[51]
D-glucose	DMMG2TO	Investigative	D-glucose increases the expression of Cyclin-dependent kinase inhibitor 2A (CDKN2A).	[52]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone increases the expression of Cyclin-dependent kinase inhibitor 2A (CDKN2A).	[53]
Lithium chloride	DMHYLQ2	Investigative	Lithium chloride increases the expression of Cyclin-dependent kinase inhibitor 2A (CDKN2A).	[54]
Cycloheximide	DMGDA3C	Investigative	Cycloheximide increases the expression of Cyclin-dependent kinase inhibitor 2A (CDKN2A).	[55]
Microcystin-LR	DMTMLRN	Investigative	Microcystin-LR decreases the expression of Cyclin-dependent kinase inhibitor 2A (CDKN2A).	[56]
Dibutyl phthalate	DMEDGKO	Investigative	Dibutyl phthalate decreases the expression of Cyclin-dependent kinase inhibitor 2A (CDKN2A).	[57]
Linalool	DMGZQ5P	Investigative	Linalool increases the expression of Cyclin-dependent kinase inhibitor 2A (CDKN2A).	[58]
GW-3965	DMG60ET	Investigative	GW-3965 increases the expression of Cyclin-dependent kinase inhibitor 2A (CDKN2A).	[59]
Wogonin	DMGCF51	Investigative	Wogonin increases the expression of Cyclin-dependent kinase inhibitor 2A (CDKN2A).	[61]
Purvalanol A	DMNQ7TM	Investigative	Purvalanol A increases the expression of Cyclin-dependent kinase inhibitor 2A (CDKN2A).	[62]
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⏷ Show the Full List of 52 Drug(s)

References

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