Details of Drug Off-Target (DOT)

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

DOT Name	Cyclin-dependent kinase inhibitor 1 (CDKN1A)
Synonyms	CDK-interacting protein 1; Melanoma differentiation-associated protein 6; MDA-6; p21
Gene Name	CDKN1A
UniProt ID	CDN1A_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	1AXC; 2ZVV; 2ZVW; 4RJF; 5E0U; 6CBI; 6CEJ; 6CIV; 6CIX; 6P8H; 7KQ0; 7KQ1
Pfam ID	PF02234
Sequence	MSEPAGDVRQNPCGSKACRRLFGPVDSEQLSRDCDALMAGCIQEARERWNFDFVTETPLE GDFAWERVRGLGLPKLYLPTGPRRGRDELGGGRRPGTSPALLQGTAEEDHVDLSLSCTLV PRSGEQAEGSPGGPGDSQGRKRRQTSMTDFYHSKRRLIFSKRKP
Function	Plays an important role in controlling cell cycle progression and DNA damage-induced G2 arrest. Involved in p53/TP53 mediated inhibition of cellular proliferation in response to DNA damage. Also involved in p53-independent DNA damage-induced G2 arrest mediated by CREB3L1 in astrocytes and osteoblasts. Binds to and inhibits cyclin-dependent kinase activity, preventing phosphorylation of critical cyclin-dependent kinase substrates and blocking cell cycle progression. Functions in the nuclear localization and assembly of cyclin D-CDK4 complex and promotes its kinase activity towards RB1. At higher stoichiometric ratios, inhibits the kinase activity of the cyclin D-CDK4 complex. Inhibits DNA synthesis by DNA polymerase delta by competing with POLD3 for PCNA binding.
Tissue Specificity	Expressed in all adult tissues, with 5-fold lower levels observed in the brain.
KEGG Pathway	Endocrine resistance (hsa01522 ) Platinum drug resistance (hsa01524 ) ErbB sig.ling pathway (hsa04012 ) HIF-1 sig.ling pathway (hsa04066 ) FoxO sig.ling pathway (hsa04068 ) Cell cycle (hsa04110 ) p53 sig.ling pathway (hsa04115 ) PI3K-Akt sig.ling pathway (hsa04151 ) Cellular senescence (hsa04218 ) JAK-STAT sig.ling pathway (hsa04630 ) Oxytocin sig.ling pathway (hsa04921 ) Parathyroid hormone synthesis, secretion and action (hsa04928 ) Cushing syndrome (hsa04934 ) Hepatitis C (hsa05160 ) Hepatitis B (hsa05161 ) Human cytomegalovirus infection (hsa05163 ) Human papillomavirus infection (hsa05165 ) Human T-cell leukemia virus 1 infection (hsa05166 ) Kaposi sarcoma-associated herpesvirus infection (hsa05167 ) Epstein-Barr virus infection (hsa05169 ) Pathways in cancer (hsa05200 ) Transcriptio.l misregulation in cancer (hsa05202 ) Viral carcinogenesis (hsa05203 ) Proteoglycans in cancer (hsa05205 ) MicroR.s in cancer (hsa05206 ) Colorectal cancer (hsa05210 ) Re.l cell carcinoma (hsa05211 ) Pancreatic cancer (hsa05212 ) Endometrial cancer (hsa05213 ) Glioma (hsa05214 ) Prostate cancer (hsa05215 ) Thyroid cancer (hsa05216 ) Basal cell carcinoma (hsa05217 ) Melanoma (hsa05218 ) Bladder cancer (hsa05219 ) Chronic myeloid leukemia (hsa05220 ) Small cell lung cancer (hsa05222 ) Non-small cell lung cancer (hsa05223 ) Breast cancer (hsa05224 ) Hepatocellular carcinoma (hsa05225 ) Gastric cancer (hsa05226 )
Reactome Pathway	AKT phosphorylates targets in the cytosol (R-HSA-198323 ) Senescence-Associated Secretory Phenotype (SASP) (R-HSA-2559582 ) DNA Damage/Telomere Stress Induced Senescence (R-HSA-2559586 ) Constitutive Signaling by AKT1 E17K in Cancer (R-HSA-5674400 ) Interleukin-4 and Interleukin-13 signaling (R-HSA-6785807 ) TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest (R-HSA-6804116 ) Cyclin E associated events during G1/S transition (R-HSA-69202 ) Cyclin D associated events in G1 (R-HSA-69231 ) p53-Dependent G1 DNA Damage Response (R-HSA-69563 ) Cyclin A (R-HSA-69656 ) Transcriptional activation of cell cycle inhibitor p21 (R-HSA-69895 ) The role of GTSE1 in G2/M progression after G2 checkpoint (R-HSA-8852276 ) TFAP2 (AP-2) family regulates transcription of cell cycle factors (R-HSA-8866911 ) Transcriptional regulation by RUNX2 (R-HSA-8878166 ) RUNX3 regulates CDKN1A transcription (R-HSA-8941855 ) Neddylation (R-HSA-8951664 ) Transcriptional regulation of granulopoiesis (R-HSA-9616222 ) FOXO-mediated transcription of cell cycle genes (R-HSA-9617828 ) Defective binding of RB1 mutants to E2F1,(E2F2, E2F3) (R-HSA-9661069 ) STAT5 activation downstream of FLT3 ITD mutants (R-HSA-9702518 ) Signaling by FLT3 fusion proteins (R-HSA-9703465 ) KEAP1-NFE2L2 pathway (R-HSA-9755511 ) SCF(Skp2)-mediated degradation of p27/p21 (R-HSA-187577 )

Molecular Interaction Atlas (MIA) of This DOT

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
Perillyl alcohol	DMFWC3O	Discontinued in Phase 2	Cyclin-dependent kinase inhibitor 1 (CDKN1A) increases the response to substance of Perillyl alcohol.	[92]
geraniol	DMS3CBD	Investigative	Cyclin-dependent kinase inhibitor 1 (CDKN1A) increases the response to substance of geraniol.	[92]
Farnesol	DMV2X1B	Investigative	Cyclin-dependent kinase inhibitor 1 (CDKN1A) increases the response to substance of Farnesol.	[92]
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2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[1]
Decitabine	DMQL8XJ	Approved	Decitabine decreases the methylation of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[21]
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97 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[7]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[8]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[9]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[10]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[11]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[12]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[13]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[14]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[15]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[16]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[17]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[18]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[19]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[20]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[22]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[23]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[24]
Menadione	DMSJDTY	Approved	Menadione increases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[14]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[25]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[26]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[27]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[28]
Folic acid	DMEMBJC	Approved	Folic acid increases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[29]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[30]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[31]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[32]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[33]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[34]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[35]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[36]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone increases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[37]
Azathioprine	DMMZSXQ	Approved	Azathioprine increases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[38]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[39]
Cytarabine	DMZD5QR	Approved	Cytarabine increases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[40]
Aspirin	DM672AH	Approved	Aspirin decreases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[41]
Etoposide	DMNH3PG	Approved	Etoposide increases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[42]
Irinotecan	DMP6SC2	Approved	Irinotecan increases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[43]
Paclitaxel	DMLB81S	Approved	Paclitaxel decreases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[30]
Diclofenac	DMPIHLS	Approved	Diclofenac increases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[44]
Nicotine	DMWX5CO	Approved	Nicotine decreases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[45]
Dasatinib	DMJV2EK	Approved	Dasatinib decreases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[47]
DTI-015	DMXZRW0	Approved	DTI-015 increases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[48]
Indomethacin	DMSC4A7	Approved	Indomethacin increases the activity of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[49]
Menthol	DMG2KW7	Approved	Menthol decreases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[50]
Mitomycin	DMH0ZJE	Approved	Mitomycin increases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[51]
Azacitidine	DMTA5OE	Approved	Azacitidine increases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[52]
Cidofovir	DMA13GD	Approved	Cidofovir increases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[53]
Simvastatin	DM30SGU	Approved	Simvastatin increases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[54]
Topotecan	DMP6G8T	Approved	Topotecan increases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[55]
Gemcitabine	DMSE3I7	Approved	Gemcitabine increases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[56]
Cyclophosphamide	DM4O2Z7	Approved	Cyclophosphamide increases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[57]
Zidovudine	DM4KI7O	Approved	Zidovudine decreases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[58]
Ifosfamide	DMCT3I8	Approved	Ifosfamide increases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[53]
Clodronate	DM9Y6X7	Approved	Clodronate increases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[53]
Sulindac	DM2QHZU	Approved	Sulindac increases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[59]
Capsaicin	DMGMF6V	Approved	Capsaicin increases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[60]
Alitretinoin	DMME8LH	Approved	Alitretinoin decreases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[61]
Lucanthone	DMZLBUO	Approved	Lucanthone increases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[62]
Daunorubicin	DMQUSBT	Approved	Daunorubicin increases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[63]
Palbociclib	DMD7L94	Approved	Palbociclib increases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[64]
Pioglitazone	DMKJ485	Approved	Pioglitazone decreases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[65]
Acocantherin	DM7JT24	Approved	Acocantherin decreases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[66]
Liothyronine	DM6IR3P	Approved	Liothyronine increases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[67]
Lindane	DMB8CNL	Approved	Lindane increases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[68]
Bicalutamide	DMZMSPF	Approved	Bicalutamide increases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[69]
Phenytoin	DMNOKBV	Approved	Phenytoin decreases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[70]
Colchicine	DM2POTE	Approved	Colchicine decreases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[30]
Hydroxyurea	DMOQVU9	Approved	Hydroxyurea increases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[71]
Gefitinib	DM15F0X	Approved	Gefitinib decreases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[72]
Diphenylpyraline	DMW4X37	Approved	Diphenylpyraline decreases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[73]
Fluoxetine	DM3PD2C	Approved	Fluoxetine increases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[74]
Sodium phenylbutyrate	DMXLBCQ	Approved	Sodium phenylbutyrate increases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[75]
Adefovir dipivoxil	DMMAWY1	Approved	Adefovir dipivoxil increases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[53]
Ritonavir	DMU764S	Approved	Ritonavir increases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[76]
Dihydroartemisinin	DMBXVMZ	Approved	Dihydroartemisinin increases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[77]
Bexarotene	DMOBIKY	Approved	Bexarotene increases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[78]
Dactinomycin	DM2YGNW	Approved	Dactinomycin decreases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[79]
Docetaxel	DMDI269	Approved	Docetaxel decreases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[40]
Cholecalciferol	DMGU74E	Approved	Cholecalciferol decreases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[80]
Adenine	DMZLHKJ	Approved	Adenine decreases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[30]
Lovastatin	DM9OZWQ	Approved	Lovastatin increases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[81]
Etretinate	DM2CZFA	Approved	Etretinate increases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[78]
Melatonin	DMKWFBT	Approved	Melatonin increases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[82]
Orlistat	DMRJSP8	Approved	Orlistat increases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[83]
Eicosapentaenoic acid/docosa-hexaenoic acid	DMMUCG4	Approved	Eicosapentaenoic acid/docosa-hexaenoic acid increases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[84]
Ximelegatran	DMU8ANS	Approved	Ximelegatran decreases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[85]
Dihydroxyacetone	DMM1LG2	Approved	Dihydroxyacetone decreases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[86]
Ciprofloxacin XR	DM2NLS9	Approved	Ciprofloxacin XR decreases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[87]
Omeprazole	DM471KJ	Approved	Omeprazole increases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[88]
Hesperetin	DMKER83	Approved	Hesperetin increases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[89]
Romidepsin	DMT5GNL	Approved	Romidepsin increases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[90]
Clotrimazole	DMMFCIH	Approved	Clotrimazole decreases the expression of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[91]
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⏷ Show the Full List of 97 Drug(s)

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Piroxicam	DMTK234	Approved	Piroxicam affects the localization of Cyclin-dependent kinase inhibitor 1 (CDKN1A).	[46]
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References

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