Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNY5LLZ)

DOT Name	Cyclin-dependent kinase inhibitor 1B (CDKN1B)
Synonyms	Cyclin-dependent kinase inhibitor p27; p27Kip1
Gene Name	CDKN1B
Related Disease	Multiple endocrine neoplasia type 4 ( ) Hereditary nonpolyposis colon cancer ( )
UniProt ID	CDN1B_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	1H27; 1JSU; 2AST; 5UQ3; 6ATH; 6P8E; 6P8F; 6P8G; 7B5L; 7B5M; 7B5R; 7OR8; 7ORG; 7ORH; 7ORS; 7ORT; 8BYA; 8BYL
Pfam ID	PF02234
Sequence	MSNVRVSNGSPSLERMDARQAEHPKPSACRNLFGPVDHEELTRDLEKHCRDMEEASQRKW NFDFQNHKPLEGKYEWQEVEKGSLPEFYYRPPRPPKGACKVPAQESQDVSGSRPAAPLIG APANSEDTHLVDPKTDPSDSQTGLAEQCAGIRKRPATDDSSTQNKRANRTEENVSDGSPN AGSVEQTPKKPGLRRRQT
Function	Important regulator of cell cycle progression. Inhibits the kinase activity of CDK2 bound to cyclin A, but has little inhibitory activity on CDK2 bound to SPDYA. Involved in G1 arrest. Potent inhibitor of cyclin E- and cyclin A-CDK2 complexes. Forms a complex with cyclin type D-CDK4 complexes and is involved in the assembly, stability, and modulation of CCND1-CDK4 complex activation. Acts either as an inhibitor or an activator of cyclin type D-CDK4 complexes depending on its phosphorylation state and/or stoichometry.
Tissue Specificity	Expressed in kidney (at protein level) . Expressed in all tissues tested . Highest levels in skeletal muscle, lowest in liver and kidney .
KEGG Pathway	Endocrine resistance (hsa01522 ) ErbB sig.ling pathway (hsa04012 ) HIF-1 sig.ling pathway (hsa04066 ) FoxO sig.ling pathway (hsa04068 ) Cell cycle (hsa04110 ) PI3K-Akt sig.ling pathway (hsa04151 ) AGE-RAGE sig.ling pathway in diabetic complications (hsa04933 ) Cushing syndrome (hsa04934 ) Measles (hsa05162 ) Human papillomavirus infection (hsa05165 ) Epstein-Barr virus infection (hsa05169 ) Pathways in cancer (hsa05200 ) Transcriptio.l misregulation in cancer (hsa05202 ) Viral carcinogenesis (hsa05203 ) MicroR.s in cancer (hsa05206 ) Prostate cancer (hsa05215 ) Chronic myeloid leukemia (hsa05220 ) Small cell lung cancer (hsa05222 ) 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 ) RHO GTPases activate CIT (R-HSA-5625900 ) Constitutive Signaling by AKT1 E17K in Cancer (R-HSA-5674400 ) 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 ) PTK6 Regulates Cell Cycle (R-HSA-8849470 ) FLT3 Signaling (R-HSA-9607240 ) FOXO-mediated transcription of cell cycle genes (R-HSA-9617828 ) Estrogen-dependent nuclear events downstream of ESR-membrane signaling (R-HSA-9634638 ) Defective binding of RB1 mutants to E2F1,(E2F2, E2F3) (R-HSA-9661069 ) SCF(Skp2)-mediated degradation of p27/p21 (R-HSA-187577 )

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Multiple endocrine neoplasia type 4	DISF4HDF	Definitive	Autosomal dominant	[1]
Hereditary nonpolyposis colon cancer	DISPA49R	Limited	Autosomal recessive	[1]
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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 5 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Mitomycin	DMH0ZJE	Approved	Cyclin-dependent kinase inhibitor 1B (CDKN1B) affects the response to substance of Mitomycin.	[93]
Gemcitabine	DMSE3I7	Approved	Cyclin-dependent kinase inhibitor 1B (CDKN1B) decreases the response to substance of Gemcitabine.	[94]
Perillyl alcohol	DMFWC3O	Discontinued in Phase 2	Cyclin-dependent kinase inhibitor 1B (CDKN1B) increases the response to substance of Perillyl alcohol.	[95]
geraniol	DMS3CBD	Investigative	Cyclin-dependent kinase inhibitor 1B (CDKN1B) increases the response to substance of geraniol.	[95]
Farnesol	DMV2X1B	Investigative	Cyclin-dependent kinase inhibitor 1B (CDKN1B) increases the response to substance of Farnesol.	[95]
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95 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 Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[6]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[8]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[10]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[11]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[12]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[13]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[14]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[15]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[16]
Marinol	DM70IK5	Approved	Marinol increases the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[17]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[18]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[19]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[20]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[21]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[22]
Folic acid	DMEMBJC	Approved	Folic acid increases the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[23]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[24]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[25]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone increases the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[26]
Etoposide	DMNH3PG	Approved	Etoposide increases the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[5]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[14]
Nicotine	DMWX5CO	Approved	Nicotine decreases the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[27]
Dasatinib	DMJV2EK	Approved	Dasatinib increases the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[28]
Indomethacin	DMSC4A7	Approved	Indomethacin decreases the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[29]
Simvastatin	DM30SGU	Approved	Simvastatin increases the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[30]
Fenofibrate	DMFKXDY	Approved	Fenofibrate decreases the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[31]
Mifepristone	DMGZQEF	Approved	Mifepristone increases the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[22]
Capsaicin	DMGMF6V	Approved	Capsaicin decreases the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[32]
Alitretinoin	DMME8LH	Approved	Alitretinoin increases the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[33]
Palbociclib	DMD7L94	Approved	Palbociclib increases the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[34]
Pioglitazone	DMKJ485	Approved	Pioglitazone increases the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[35]
Acetic Acid, Glacial	DM4SJ5Y	Approved	Acetic Acid, Glacial increases the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[36]
Motexafin gadolinium	DMEJKRF	Approved	Motexafin gadolinium increases the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[36]
Liothyronine	DM6IR3P	Approved	Liothyronine decreases the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[37]
Bicalutamide	DMZMSPF	Approved	Bicalutamide increases the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[38]
Hydroxyurea	DMOQVU9	Approved	Hydroxyurea increases the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[39]
Enzalutamide	DMGL19D	Approved	Enzalutamide affects the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[40]
Sorafenib	DMS8IFC	Approved	Sorafenib increases the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[41]
Gefitinib	DM15F0X	Approved	Gefitinib increases the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[28]
Fluoxetine	DM3PD2C	Approved	Fluoxetine affects the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[42]
Ritonavir	DMU764S	Approved	Ritonavir increases the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[43]
Cholecalciferol	DMGU74E	Approved	Cholecalciferol increases the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[45]
Lovastatin	DM9OZWQ	Approved	Lovastatin increases the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[46]
Ardeparin	DMYRX8B	Approved	Ardeparin decreases the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[47]
Orlistat	DMRJSP8	Approved	Orlistat increases the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[48]
Hesperetin	DMKER83	Approved	Hesperetin increases the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[49]
Clotrimazole	DMMFCIH	Approved	Clotrimazole increases the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[50]
Lapatinib	DM3BH1Y	Approved	Lapatinib increases the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[51]
Prednisone	DM2HG4X	Approved	Prednisone increases the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[52]
Digitoxin	DMWVIGP	Approved	Digitoxin decreases the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[53]
SR141716A	DMCO5JZ	Approved	SR141716A increases the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[54]
Hesperidin	DMI5DW1	Approved	Hesperidin increases the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[55]
Thiazolidinedione	DMC1NBW	Approved	Thiazolidinedione increases the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[56]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone decreases the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[57]
Berberine	DMC5Q8X	Phase 4	Berberine increases the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[58]
Isoflavone	DM7U58J	Phase 4	Isoflavone increases the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[59]
Silymarin	DMXBYQR	Phase 4	Silymarin increases the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[60]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[61]
Curcumin	DMQPH29	Phase 3	Curcumin increases the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[62]
Fenretinide	DMRD5SP	Phase 3	Fenretinide increases the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[63]
Seocalcitol	DMKL9QO	Phase 3	Seocalcitol increases the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[45]
Atorvastatin	DMF28YC	Phase 3 Trial	Atorvastatin increases the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[64]
I3C	DMIGFOR	Phase 3	I3C increases the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[65]
EXISULIND	DMBY56U	Phase 3	EXISULIND increases the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[66]
Rubitecan	DMDWU1S	Phase 3	Rubitecan increases the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[67]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[68]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[69]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene increases the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[51]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate decreases the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[70]
Disulfiram	DMCL2OK	Phase 2 Trial	Disulfiram increases the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[71]
GDC0941	DM1YAK6	Phase 2	GDC0941 increases the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[72]
URSOLIC ACID	DM4SOAW	Phase 2	URSOLIC ACID increases the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[74]
PF-04691502	DMS610L	Phase 2	PF-04691502 increases the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[75]
INK128	DMGO7QT	Phase 2	INK128 increases the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[76]
Amsilarotene	DMOB01U	Phase 2	Amsilarotene increases the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[77]
Preverex	DMZT8FS	Phase 2	Preverex increases the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[78]
Inecalcitol oral	DMU5SZP	Phase 2	Inecalcitol oral increases the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[79]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[80]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[81]
Mivebresib	DMCPF90	Phase 1	Mivebresib increases the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[82]
LY294002	DMY1AFS	Phase 1	LY294002 increases the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[10]
Tetrandrine	DMAOJBX	Phase 1	Tetrandrine increases the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[83]
AT7519	DMCE08M	Phase 1	AT7519 increases the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[85]
VS-5584	DMMO3G5	Phase 1	VS-5584 increases the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[86]
AMG 900	DMASGXJ	Phase 1	AMG 900 increases the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[87]
L-Cysteine	DMCMOS8	Clinical trial	L-Cysteine decreases the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[88]
Eugenol	DM7US1H	Patented	Eugenol increases the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[89]
PMID26394986-Compound-22	DM43Z1G	Patented	PMID26394986-Compound-22 increases the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[91]
Flavonoid derivative 1	DMCQP0B	Patented	Flavonoid derivative 1 increases the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[10]
Steroid derivative 1	DMB0NVQ	Patented	Steroid derivative 1 increases the expression of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[92]
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⏷ Show the Full List of 95 Drug(s)

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[9]
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4 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Chenodiol	DMQ8JIK	Approved	Chenodiol affects the localization of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[44]
Flavopiridol	DMKSUOI	Phase 2	Flavopiridol increases the cleavage of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[73]
IRX4204	DM9SCME	Phase 1	IRX4204 increases the stability of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[84]
PMID27336223-Compound-5	DM6E50A	Patented	PMID27336223-Compound-5 affects the localization of Cyclin-dependent kinase inhibitor 1B (CDKN1B).	[90]
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