Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTR95N0X)

DOT Name	Cyclin-dependent kinase 6 (CDK6)
Synonyms	EC 2.7.11.22; Cell division protein kinase 6; Serine/threonine-protein kinase PLSTIRE
Gene Name	CDK6
Related Disease	Autosomal recessive primary microcephaly ( ) Microcephaly 12, primary, autosomal recessive ( )
UniProt ID	CDK6_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	1BI7; 1BI8; 1BLX; 1G3N; 1JOW; 1XO2; 2EUF; 2F2C; 3NUP; 3NUX; 4AUA; 4EZ5; 4TTH; 5L2I; 5L2S; 5L2T; 6OQL; 6OQO
EC Number	2.7.11.22
Pfam ID	PF00069
Sequence	MEKDGLCRADQQYECVAEIGEGAYGKVFKARDLKNGGRFVALKRVRVQTGEEGMPLSTIR EVAVLRHLETFEHPNVVRLFDVCTVSRTDRETKLTLVFEHVDQDLTTYLDKVPEPGVPTE TIKDMMFQLLRGLDFLHSHRVVHRDLKPQNILVTSSGQIKLADFGLARIYSFQMALTSVV VTLWYRAPEVLLQSSYATPVDLWSVGCIFAEMFRRKPLFRGSSDVDQLGKILDVIGLPGE EDWPRDVALPRQAFHSKSAQPIEKFVTDIDELGKDLLLKCLTFNPAKRISAYSALSHPYF QDLERCKENLDSHLPPSQNTSELNTA
Function	Serine/threonine-protein kinase involved in the control of the cell cycle and differentiation; promotes G1/S transition. Phosphorylates pRB/RB1 and NPM1. Interacts with D-type G1 cyclins during interphase at G1 to form a pRB/RB1 kinase and controls the entrance into the cell cycle. Involved in initiation and maintenance of cell cycle exit during cell differentiation; prevents cell proliferation and negatively regulates cell differentiation, but is required for the proliferation of specific cell types (e.g. erythroid and hematopoietic cells). Essential for cell proliferation within the dentate gyrus of the hippocampus and the subventricular zone of the lateral ventricles. Required during thymocyte development. Promotes the production of newborn neurons, probably by modulating G1 length. Promotes, at least in astrocytes, changes in patterns of gene expression, changes in the actin cytoskeleton including loss of stress fibers, and enhanced motility during cell differentiation. Prevents myeloid differentiation by interfering with RUNX1 and reducing its transcription transactivation activity, but promotes proliferation of normal myeloid progenitors. Delays senescence. Promotes the proliferation of beta-cells in pancreatic islets of Langerhans. May play a role in the centrosome organization during the cell cycle phases.
Tissue Specificity	Expressed ubiquitously. Accumulates in squamous cell carcinomas, proliferating hematopoietic progenitor cells, beta-cells of pancreatic islets of Langerhans, and neuroblastomas. Reduced levels in differentiating cells.
KEGG Pathway	Cell cycle (hsa04110 ) p53 sig.ling pathway (hsa04115 ) PI3K-Akt sig.ling pathway (hsa04151 ) Cellular senescence (hsa04218 ) Cushing syndrome (hsa04934 ) Hepatitis C (hsa05160 ) Measles (hsa05162 ) Human cytomegalovirus infection (hsa05163 ) Influenza A (hsa05164 ) Human papillomavirus infection (hsa05165 ) Kaposi sarcoma-associated herpesvirus infection (hsa05167 ) Epstein-Barr virus infection (hsa05169 ) Pathways in cancer (hsa05200 ) Viral carcinogenesis (hsa05203 ) MicroR.s in cancer (hsa05206 ) Pancreatic cancer (hsa05212 ) Glioma (hsa05214 ) Melanoma (hsa05218 ) Chronic myeloid leukemia (hsa05220 ) Small cell lung cancer (hsa05222 ) Non-small cell lung cancer (hsa05223 ) Breast cancer (hsa05224 ) 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 ) Regulation of RUNX1 Expression and Activity (R-HSA-8934593 ) 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 and CDK6 (R-HSA-9632700 ) Defective binding of RB1 mutants to E2F1,(E2F2, E2F3) (R-HSA-9661069 ) Drug-mediated inhibition of CDK4/CDK6 activity (R-HSA-9754119 ) Oxidative Stress Induced Senescence (R-HSA-2559580 )

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Autosomal recessive primary microcephaly	DIS29IE3	Supportive	Autosomal recessive	[1]
Microcephaly 12, primary, autosomal recessive	DIS71V6D	Limited	Unknown	[1]
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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

77 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 6 (CDK6).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Cyclin-dependent kinase 6 (CDK6).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Cyclin-dependent kinase 6 (CDK6).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Cyclin-dependent kinase 6 (CDK6).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Cyclin-dependent kinase 6 (CDK6).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Cyclin-dependent kinase 6 (CDK6).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Cyclin-dependent kinase 6 (CDK6).	[8]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Cyclin-dependent kinase 6 (CDK6).	[9]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Cyclin-dependent kinase 6 (CDK6).	[10]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of Cyclin-dependent kinase 6 (CDK6).	[11]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Cyclin-dependent kinase 6 (CDK6).	[12]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Cyclin-dependent kinase 6 (CDK6).	[13]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Cyclin-dependent kinase 6 (CDK6).	[14]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Cyclin-dependent kinase 6 (CDK6).	[15]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Cyclin-dependent kinase 6 (CDK6).	[16]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Cyclin-dependent kinase 6 (CDK6).	[17]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Cyclin-dependent kinase 6 (CDK6).	[18]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Cyclin-dependent kinase 6 (CDK6).	[15]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the expression of Cyclin-dependent kinase 6 (CDK6).	[19]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of Cyclin-dependent kinase 6 (CDK6).	[20]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Cyclin-dependent kinase 6 (CDK6).	[21]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the expression of Cyclin-dependent kinase 6 (CDK6).	[22]
Irinotecan	DMP6SC2	Approved	Irinotecan affects the expression of Cyclin-dependent kinase 6 (CDK6).	[23]
Paclitaxel	DMLB81S	Approved	Paclitaxel decreases the expression of Cyclin-dependent kinase 6 (CDK6).	[24]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of Cyclin-dependent kinase 6 (CDK6).	[17]
Nicotine	DMWX5CO	Approved	Nicotine increases the expression of Cyclin-dependent kinase 6 (CDK6).	[25]
Ifosfamide	DMCT3I8	Approved	Ifosfamide affects the expression of Cyclin-dependent kinase 6 (CDK6).	[22]
Clodronate	DM9Y6X7	Approved	Clodronate affects the expression of Cyclin-dependent kinase 6 (CDK6).	[22]
Sulindac	DM2QHZU	Approved	Sulindac decreases the expression of Cyclin-dependent kinase 6 (CDK6).	[26]
Ibuprofen	DM8VCBE	Approved	Ibuprofen decreases the expression of Cyclin-dependent kinase 6 (CDK6).	[22]
Acocantherin	DM7JT24	Approved	Acocantherin decreases the expression of Cyclin-dependent kinase 6 (CDK6).	[27]
Sorafenib	DMS8IFC	Approved	Sorafenib decreases the expression of Cyclin-dependent kinase 6 (CDK6).	[28]
Gefitinib	DM15F0X	Approved	Gefitinib decreases the expression of Cyclin-dependent kinase 6 (CDK6).	[29]
Adefovir dipivoxil	DMMAWY1	Approved	Adefovir dipivoxil increases the expression of Cyclin-dependent kinase 6 (CDK6).	[22]
Ritonavir	DMU764S	Approved	Ritonavir decreases the expression of Cyclin-dependent kinase 6 (CDK6).	[30]
Cantharidin	DMBP5N3	Approved	Cantharidin decreases the expression of Cyclin-dependent kinase 6 (CDK6).	[31]
AC220	DM8Y4JS	Approved	AC220 decreases the expression of Cyclin-dependent kinase 6 (CDK6).	[32]
Dronedarone	DMA8FS5	Approved	Dronedarone decreases the expression of Cyclin-dependent kinase 6 (CDK6).	[33]
Furazolidone	DM3P6V7	Approved	Furazolidone increases the expression of Cyclin-dependent kinase 6 (CDK6).	[34]
Hesperidin	DMI5DW1	Approved	Hesperidin decreases the expression of Cyclin-dependent kinase 6 (CDK6).	[36]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Cyclin-dependent kinase 6 (CDK6).	[37]
Berberine	DMC5Q8X	Phase 4	Berberine decreases the expression of Cyclin-dependent kinase 6 (CDK6).	[38]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Cyclin-dependent kinase 6 (CDK6).	[39]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate decreases the expression of Cyclin-dependent kinase 6 (CDK6).	[40]
Curcumin	DMQPH29	Phase 3	Curcumin decreases the expression of Cyclin-dependent kinase 6 (CDK6).	[41]
I3C	DMIGFOR	Phase 3	I3C decreases the expression of Cyclin-dependent kinase 6 (CDK6).	[42]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Cyclin-dependent kinase 6 (CDK6).	[43]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate increases the expression of Cyclin-dependent kinase 6 (CDK6).	[44]
OTX-015	DMI8RG1	Phase 1/2	OTX-015 decreases the expression of Cyclin-dependent kinase 6 (CDK6).	[45]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Cyclin-dependent kinase 6 (CDK6).	[46]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Cyclin-dependent kinase 6 (CDK6).	[47]
Mivebresib	DMCPF90	Phase 1	Mivebresib decreases the expression of Cyclin-dependent kinase 6 (CDK6).	[45]
TAK-114	DMTXE19	Phase 1	TAK-114 decreases the expression of Cyclin-dependent kinase 6 (CDK6).	[48]
IRX4204	DM9SCME	Phase 1	IRX4204 decreases the expression of Cyclin-dependent kinase 6 (CDK6).	[49]
AMG 900	DMASGXJ	Phase 1	AMG 900 decreases the expression of Cyclin-dependent kinase 6 (CDK6).	[50]
Eugenol	DM7US1H	Patented	Eugenol decreases the expression of Cyclin-dependent kinase 6 (CDK6).	[52]
PMID25656651-Compound-5	DMAI95U	Patented	PMID25656651-Compound-5 decreases the expression of Cyclin-dependent kinase 6 (CDK6).	[32]
Geldanamycin	DMS7TC5	Discontinued in Phase 2	Geldanamycin increases the expression of Cyclin-dependent kinase 6 (CDK6).	[53]
Torcetrapib	DMDHYM7	Discontinued in Phase 2	Torcetrapib increases the expression of Cyclin-dependent kinase 6 (CDK6).	[54]
Dioscin	DM5H2W9	Preclinical	Dioscin decreases the expression of Cyclin-dependent kinase 6 (CDK6).	[55]
Piperlongumine	DMIZCOE	Preclinical	Piperlongumine decreases the expression of Cyclin-dependent kinase 6 (CDK6).	[56]
EMBELIN	DMFZO4Y	Terminated	EMBELIN decreases the expression of Cyclin-dependent kinase 6 (CDK6).	[57]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Cyclin-dependent kinase 6 (CDK6).	[58]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Cyclin-dependent kinase 6 (CDK6).	[59]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Cyclin-dependent kinase 6 (CDK6).	[60]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Cyclin-dependent kinase 6 (CDK6).	[61]
Deguelin	DMXT7WG	Investigative	Deguelin increases the expression of Cyclin-dependent kinase 6 (CDK6).	[62]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate decreases the expression of Cyclin-dependent kinase 6 (CDK6).	[9]
Glyphosate	DM0AFY7	Investigative	Glyphosate increases the expression of Cyclin-dependent kinase 6 (CDK6).	[44]
Butanoic acid	DMTAJP7	Investigative	Butanoic acid decreases the expression of Cyclin-dependent kinase 6 (CDK6).	[63]
Galangin	DM5TQ2O	Investigative	Galangin decreases the expression of Cyclin-dependent kinase 6 (CDK6).	[64]
I-BET151	DMYRUH2	Investigative	I-BET151 decreases the expression of Cyclin-dependent kinase 6 (CDK6).	[65]
USNIC ACID	DMGOURX	Investigative	USNIC ACID decreases the expression of Cyclin-dependent kinase 6 (CDK6).	[66]
BAY11-7082	DMQNOFA	Investigative	BAY11-7082 decreases the expression of Cyclin-dependent kinase 6 (CDK6).	[67]
DIECKOL	DMBCK4G	Investigative	DIECKOL decreases the expression of Cyclin-dependent kinase 6 (CDK6).	[24]
tryptanthrin	DMTRYCI	Investigative	tryptanthrin decreases the expression of Cyclin-dependent kinase 6 (CDK6).	[68]
MDA-19	DMEUWB8	Investigative	MDA-19 decreases the expression of Cyclin-dependent kinase 6 (CDK6).	[69]
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⏷ Show the Full List of 77 Drug(s)

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tetracaine	DM9J6C2	Approved	Tetracaine decreases the phosphorylation of Cyclin-dependent kinase 6 (CDK6).	[35]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Cyclin-dependent kinase 6 (CDK6).	[51]
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References

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