Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTW1SC2N)

• DOT Name: Cyclin-dependent kinase 1 (CDK1)
• Synonyms: CDK1; EC 2.7.11.22; EC 2.7.11.23; Cell division control protein 2 homolog; Cell division protein kinase 1; p34 protein kinase
• Gene Name: CDK1
• UniProt ID: CDK1_HUMAN
• PDB ID: 4Y72; 4YC3; 4YC6; 5HQ0; 5LQF; 6GU2; 6GU3; 6GU4; 6GU6; 6GU7; 6TWN; 7NJ0
• EC Number: 2.7.11.22; 2.7.11.23
• Pfam ID: PF00069
• Sequence:
  MEDYTKIEKIGEGTYGVVYKGRHKTTGQVVAMKKIRLESEEEGVPSTAIREISLLKELRH
  PNIVSLQDVLMQDSRLYLIFEFLSMDLKKYLDSIPPGQYMDSSLVKSYLYQILQGIVFCH
  SRRVLHRDLKPQNLLIDDKGTIKLADFGLARAFGIPIRVYTHEVVTLWYRSPEVLLGSAR
  YSTPVDIWSIGTIFAELATKKPLFHGDSEIDQLFRIFRALGTPNNEVWPEVESLQDYKNT
  FPKWKPGSLASHVKNLDENGLDLLSKMLIYDPAKRISGKMALNHPYFNDLDNQIKKM
• Function: Plays a key role in the control of the eukaryotic cell cycle by modulating the centrosome cycle as well as mitotic onset; promotes G2-M transition via association with multiple interphase cyclins. Phosphorylates PARVA/actopaxin, APC, AMPH, APC, BARD1, Bcl-xL/BCL2L1, BRCA2, CALD1, CASP8, CDC7, CDC20, CDC25A, CDC25C, CC2D1A, CENPA, CSNK2 proteins/CKII, FZR1/CDH1, CDK7, CEBPB, CHAMP1, DMD/dystrophin, EEF1 proteins/EF-1, EZH2, KIF11/EG5, EGFR, FANCG, FOS, GFAP, GOLGA2/GM130, GRASP1, UBE2A/hHR6A, HIST1H1 proteins/histone H1, HMGA1, HIVEP3/KRC, KAT5, LMNA, LMNB, LBR, LATS1, MAP1B, MAP4, MARCKS, MCM2, MCM4, MKLP1, MLST8, MYB, NEFH, NFIC, NPC/nuclear pore complex, PITPNM1/NIR2, NPM1, NCL, NUCKS1, NPM1/numatrin, ORC1, PRKAR2A, EEF1E1/p18, EIF3F/p47, p53/TP53, NONO/p54NRB, PAPOLA, PLEC/plectin, RB1, TPPP, UL40/R2, RAB4A, RAP1GAP, RCC1, RPS6KB1/S6K1, KHDRBS1/SAM68, ESPL1, SKI, BIRC5/survivin, STIP1, TEX14, beta-tubulins, MAPT/TAU, NEDD1, VIM/vimentin, TK1, FOXO1, RUNX1/AML1, SAMHD1, SIRT2, CGAS and RUNX2. CDK1/CDC2-cyclin-B controls pronuclear union in interphase fertilized eggs. Essential for early stages of embryonic development. During G2 and early mitosis, CDC25A/B/C-mediated dephosphorylation activates CDK1/cyclin complexes which phosphorylate several substrates that trigger at least centrosome separation, Golgi dynamics, nuclear envelope breakdown and chromosome condensation. Once chromosomes are condensed and aligned at the metaphase plate, CDK1 activity is switched off by WEE1- and PKMYT1-mediated phosphorylation to allow sister chromatid separation, chromosome decondensation, reformation of the nuclear envelope and cytokinesis. Phosphorylates KRT5 during prometaphase and metaphase. Inactivated by PKR/EIF2AK2- and WEE1-mediated phosphorylation upon DNA damage to stop cell cycle and genome replication at the G2 checkpoint thus facilitating DNA repair. Reactivated after successful DNA repair through WIP1-dependent signaling leading to CDC25A/B/C-mediated dephosphorylation and restoring cell cycle progression. Catalyzes lamin (LMNA, LMNB1 and LMNB2) phosphorylation at the onset of mitosis, promoting nuclear envelope breakdown. In proliferating cells, CDK1-mediated FOXO1 phosphorylation at the G2-M phase represses FOXO1 interaction with 14-3-3 proteins and thereby promotes FOXO1 nuclear accumulation and transcription factor activity, leading to cell death of postmitotic neurons. The phosphorylation of beta-tubulins regulates microtubule dynamics during mitosis. NEDD1 phosphorylation promotes PLK1-mediated NEDD1 phosphorylation and subsequent targeting of the gamma-tubulin ring complex (gTuRC) to the centrosome, an important step for spindle formation. In addition, CC2D1A phosphorylation regulates CC2D1A spindle pole localization and association with SCC1/RAD21 and centriole cohesion during mitosis. The phosphorylation of Bcl-xL/BCL2L1 after prolongated G2 arrest upon DNA damage triggers apoptosis. In contrast, CASP8 phosphorylation during mitosis prevents its activation by proteolysis and subsequent apoptosis. This phosphorylation occurs in cancer cell lines, as well as in primary breast tissues and lymphocytes. EZH2 phosphorylation promotes H3K27me3 maintenance and epigenetic gene silencing. CALD1 phosphorylation promotes Schwann cell migration during peripheral nerve regeneration. CDK1-cyclin-B complex phosphorylates NCKAP5L and mediates its dissociation from centrosomes during mitosis. Regulates the amplitude of the cyclic expression of the core clock gene BMAL1 by phosphorylating its transcriptional repressor NR1D1, and this phosphorylation is necessary for SCF(FBXW7)-mediated ubiquitination and proteasomal degradation of NR1D1. Phosphorylates EML3 at 'Thr-881' which is essential for its interaction with HAUS augmin-like complex and TUBG1. Phosphorylates CGAS during mitosis, leading to its inhibition, thereby preventing CGAS activation by self DNA during mitosis ; (Microbial infection) Acts as a receptor for hepatitis C virus (HCV) in hepatocytes and facilitates its cell entry.
• Tissue Specificity: .Found in breast cancer tissues.
• KEGG Pathway:
  Cell cycle (hsa04110)
  Oocyte meiosis (hsa04114)
  p53 sig.ling pathway (hsa04115)
  Cellular senescence (hsa04218)
  Gap junction (hsa04540)
  Progesterone-mediated oocyte maturation (hsa04914)
  Human immunodeficiency virus 1 infection (hsa05170)
  Viral carcinogenesis (hsa05203)
• Reactome Pathway:
  E2F-enabled inhibition of pre-replication complex formation (R-HSA-113507)
  Transcription of E2F targets under negative control by p107 (RBL1) and p130 (RBL2) in complex with HDAC1 (R-HSA-1362300)
  Golgi Cisternae Pericentriolar Stack Reorganization (R-HSA-162658)
  Phosphorylation of proteins involved in the G2/M transition by Cyclin A (R-HSA-170145)
  APC/C (R-HSA-174048)
  Cdc20 (R-HSA-174184)
  Regulation of APC/C activators between G1/S and early anaphase (R-HSA-176408)
  Phosphorylation of the APC/C (R-HSA-176412)
  Phosphorylation of Emi1 (R-HSA-176417)
  Condensation of Prophase Chromosomes (R-HSA-2299718)
  MASTL Facilitates Mitotic Progression (R-HSA-2465910)
  Resolution of Sister Chromatid Cohesion (R-HSA-2500257)
  Condensation of Prometaphase Chromosomes (R-HSA-2514853)
  Regulation of PLK1 Activity at G2/M Transition (R-HSA-2565942)
  Activation of NIMA Kinases NEK9, NEK6, NEK7 (R-HSA-2980767)
  Initiation of Nuclear Envelope (NE) Reformation (R-HSA-2995383)
  Nuclear Pore Complex (NPC) Disassembly (R-HSA-3301854)
  Loss of Nlp from mitotic centrosomes (R-HSA-380259)
  Recruitment of mitotic centrosome proteins and complexes (R-HSA-380270)
  Loss of proteins required for interphase microtubule organization from the centrosome (R-HSA-380284)
  Recruitment of NuMA to mitotic centrosomes (R-HSA-380320)
  Depolymerization of the Nuclear Lamina (R-HSA-4419969)
  Anchoring of the basal body to the plasma membrane (R-HSA-5620912)
  MAPK6/MAPK4 signaling (R-HSA-5687128)
  Ovarian tumor domain proteases (R-HSA-5689896)
  TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest (R-HSA-6804114)
  Regulation of TP53 Degradation (R-HSA-6804757)
  Mitotic Prophase (R-HSA-68875)
  G1/S-Specific Transcription (R-HSA-69205)
  Cyclin A/B1/B2 associated events during G2/M transition (R-HSA-69273)
  G2/M DNA replication checkpoint (R-HSA-69478)
  Chk1/Chk2(Cds1) mediated inactivation of Cyclin B (R-HSA-75035)
  The role of GTSE1 in G2/M progression after G2 checkpoint (R-HSA-8852276)
  AURKA Activation by TPX2 (R-HSA-8854518)
  Transcriptional regulation by RUNX2 (R-HSA-8878166)
  PKR-mediated signaling (R-HSA-9833482)
  MAPK3 (ERK1) activation (R-HSA-110056)

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Vinblastine	DM5TVS3	Approved	Cyclin-dependent kinase 1 (CDK1) affects the response to substance of Vinblastine.	[94]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Cyclin-dependent kinase 1 (CDK1).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Cyclin-dependent kinase 1 (CDK1).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Cyclin-dependent kinase 1 (CDK1).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Cyclin-dependent kinase 1 (CDK1).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Cyclin-dependent kinase 1 (CDK1).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Cyclin-dependent kinase 1 (CDK1).	[6]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Cyclin-dependent kinase 1 (CDK1).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Cyclin-dependent kinase 1 (CDK1).	[8]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of Cyclin-dependent kinase 1 (CDK1).	[9]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Cyclin-dependent kinase 1 (CDK1).	[10]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Cyclin-dependent kinase 1 (CDK1).	[11]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Cyclin-dependent kinase 1 (CDK1).	[12]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Cyclin-dependent kinase 1 (CDK1).	[13]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Cyclin-dependent kinase 1 (CDK1).	[14]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Cyclin-dependent kinase 1 (CDK1).	[15]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Cyclin-dependent kinase 1 (CDK1).	[14]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Cyclin-dependent kinase 1 (CDK1).	[16]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Cyclin-dependent kinase 1 (CDK1).	[18]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Cyclin-dependent kinase 1 (CDK1).	[19]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Cyclin-dependent kinase 1 (CDK1).	[20]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Cyclin-dependent kinase 1 (CDK1).	[21]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Cyclin-dependent kinase 1 (CDK1).	[4]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the expression of Cyclin-dependent kinase 1 (CDK1).	[22]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Cyclin-dependent kinase 1 (CDK1).	[23]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of Cyclin-dependent kinase 1 (CDK1).	[24]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of Cyclin-dependent kinase 1 (CDK1).	[25]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the activity of Cyclin-dependent kinase 1 (CDK1).	[26]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Cyclin-dependent kinase 1 (CDK1).	[27]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Cyclin-dependent kinase 1 (CDK1).	[28]
Irinotecan	DMP6SC2	Approved	Irinotecan decreases the expression of Cyclin-dependent kinase 1 (CDK1).	[29]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Cyclin-dependent kinase 1 (CDK1).	[30]
Paclitaxel	DMLB81S	Approved	Paclitaxel decreases the expression of Cyclin-dependent kinase 1 (CDK1).	[31]
Nicotine	DMWX5CO	Approved	Nicotine increases the expression of Cyclin-dependent kinase 1 (CDK1).	[32]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Cyclin-dependent kinase 1 (CDK1).	[33]
Dasatinib	DMJV2EK	Approved	Dasatinib decreases the expression of Cyclin-dependent kinase 1 (CDK1).	[34]
Azacitidine	DMTA5OE	Approved	Azacitidine increases the expression of Cyclin-dependent kinase 1 (CDK1).	[35]
Simvastatin	DM30SGU	Approved	Simvastatin decreases the expression of Cyclin-dependent kinase 1 (CDK1).	[36]
Mifepristone	DMGZQEF	Approved	Mifepristone increases the expression of Cyclin-dependent kinase 1 (CDK1).	[37]
Sulindac	DM2QHZU	Approved	Sulindac decreases the expression of Cyclin-dependent kinase 1 (CDK1).	[38]
Lucanthone	DMZLBUO	Approved	Lucanthone decreases the expression of Cyclin-dependent kinase 1 (CDK1).	[39]
Palbociclib	DMD7L94	Approved	Palbociclib decreases the expression of Cyclin-dependent kinase 1 (CDK1).	[40]
Bicalutamide	DMZMSPF	Approved	Bicalutamide decreases the expression of Cyclin-dependent kinase 1 (CDK1).	[41]
Imatinib	DM7RJXL	Approved	Imatinib decreases the expression of Cyclin-dependent kinase 1 (CDK1).	[42]
Bexarotene	DMOBIKY	Approved	Bexarotene decreases the expression of Cyclin-dependent kinase 1 (CDK1).	[43]
Docetaxel	DMDI269	Approved	Docetaxel increases the activity of Cyclin-dependent kinase 1 (CDK1).	[26]
Etretinate	DM2CZFA	Approved	Etretinate decreases the expression of Cyclin-dependent kinase 1 (CDK1).	[43]
Propofol	DMB4OLE	Approved	Propofol decreases the expression of Cyclin-dependent kinase 1 (CDK1).	[44]
Melatonin	DMKWFBT	Approved	Melatonin decreases the expression of Cyclin-dependent kinase 1 (CDK1).	[45]
Orlistat	DMRJSP8	Approved	Orlistat decreases the expression of Cyclin-dependent kinase 1 (CDK1).	[46]
Clotrimazole	DMMFCIH	Approved	Clotrimazole decreases the expression of Cyclin-dependent kinase 1 (CDK1).	[47]
Clofibrate	DMPC1J7	Approved	Clofibrate decreases the expression of Cyclin-dependent kinase 1 (CDK1).	[48]
Gamolenic acid	DMQN30Z	Approved	Gamolenic acid decreases the expression of Cyclin-dependent kinase 1 (CDK1).	[49]
Omacetaxine mepesuccinate	DMPU2WX	Approved	Omacetaxine mepesuccinate increases the expression of Cyclin-dependent kinase 1 (CDK1).	[50]
Digitoxin	DMWVIGP	Approved	Digitoxin decreases the expression of Cyclin-dependent kinase 1 (CDK1).	[51]
Mechlorethamine	DM0CVXA	Approved	Mechlorethamine decreases the activity of Cyclin-dependent kinase 1 (CDK1).	[52]
Atropine	DMEN6X7	Approved	Atropine increases the expression of Cyclin-dependent kinase 1 (CDK1).	[53]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Cyclin-dependent kinase 1 (CDK1).	[56]
Silymarin	DMXBYQR	Phase 4	Silymarin decreases the expression of Cyclin-dependent kinase 1 (CDK1).	[57]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Cyclin-dependent kinase 1 (CDK1).	[58]
Curcumin	DMQPH29	Phase 3	Curcumin decreases the expression of Cyclin-dependent kinase 1 (CDK1).	[59]
Fenretinide	DMRD5SP	Phase 3	Fenretinide decreases the expression of Cyclin-dependent kinase 1 (CDK1).	[60]
Rigosertib	DMOSTXF	Phase 3	Rigosertib increases the expression of Cyclin-dependent kinase 1 (CDK1).	[61]
Triptolide	DMCMDVR	Phase 3	Triptolide decreases the expression of Cyclin-dependent kinase 1 (CDK1).	[62]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Cyclin-dependent kinase 1 (CDK1).	[64]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of Cyclin-dependent kinase 1 (CDK1).	[65]
GSK2110183	DMZHB37	Phase 2	GSK2110183 decreases the expression of Cyclin-dependent kinase 1 (CDK1).	[66]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene increases the expression of Cyclin-dependent kinase 1 (CDK1).	[67]
Tanespimycin	DMNLQHK	Phase 2	Tanespimycin decreases the expression of Cyclin-dependent kinase 1 (CDK1).	[68]
Flavopiridol	DMKSUOI	Phase 2	Flavopiridol decreases the activity of Cyclin-dependent kinase 1 (CDK1).	[71]
MGCD-0103	DM726HX	Phase 2	MGCD-0103 decreases the expression of Cyclin-dependent kinase 1 (CDK1).	[72]
Preverex	DMZT8FS	Phase 2	Preverex decreases the expression of Cyclin-dependent kinase 1 (CDK1).	[73]
Plevitrexed	DM7Y60I	Phase 2	Plevitrexed increases the expression of Cyclin-dependent kinase 1 (CDK1).	[74]
AXL-1717	DMTQ1Y3	Phase 2	AXL-1717 decreases the activity of Cyclin-dependent kinase 1 (CDK1).	[76]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Cyclin-dependent kinase 1 (CDK1).	[78]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Cyclin-dependent kinase 1 (CDK1).	[79]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Cyclin-dependent kinase 1 (CDK1).	[80]
Mivebresib	DMCPF90	Phase 1	Mivebresib decreases the expression of Cyclin-dependent kinase 1 (CDK1).	[82]
Arecoline	DMFJZK3	Phase 1	Arecoline decreases the activity of Cyclin-dependent kinase 1 (CDK1).	[83]
TAK-114	DMTXE19	Phase 1	TAK-114 decreases the expression of Cyclin-dependent kinase 1 (CDK1).	[84]
IRX4204	DM9SCME	Phase 1	IRX4204 decreases the expression of Cyclin-dependent kinase 1 (CDK1).	[49]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Cyclin-dependent kinase 1 (CDK1).	[85]
Flavonoid derivative 1	DMCQP0B	Patented	Flavonoid derivative 1 decreases the expression of Cyclin-dependent kinase 1 (CDK1).	[86]
Harmine	DMPA5WD	Patented	Harmine increases the expression of Cyclin-dependent kinase 1 (CDK1).	[88]
PMID26882240-Compound-32	DMJS4RP	Patented	PMID26882240-Compound-32 decreases the expression of Cyclin-dependent kinase 1 (CDK1).	[68]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Cyclin-dependent kinase 1 (CDK1).	[89]
Dioscin	DM5H2W9	Preclinical	Dioscin decreases the expression of Cyclin-dependent kinase 1 (CDK1).	[90]
Ciglitazone	DMAPO0T	Preclinical	Ciglitazone decreases the expression of Cyclin-dependent kinase 1 (CDK1).	[48]
BMS-3870032	DMCWIBU	Preclinical	BMS-3870032 decreases the activity of Cyclin-dependent kinase 1 (CDK1).	[91]
Pifithrin-alpha	DM63OD7	Terminated	Pifithrin-alpha increases the expression of Cyclin-dependent kinase 1 (CDK1).	[92]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Cyclin-dependent kinase 1 (CDK1).	[93]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Decitabine	DMQL8XJ	Approved	Decitabine increases the phosphorylation of Cyclin-dependent kinase 1 (CDK1).	[17]
Desloratadine	DM56YN7	Approved	Desloratadine increases the phosphorylation of Cyclin-dependent kinase 1 (CDK1).	[54]
Amifostine	DM5FL14	Approved	Amifostine decreases the phosphorylation of Cyclin-dependent kinase 1 (CDK1).	[55]
VAL-083	DM9J5Q4	Phase 3	VAL-083 increases the phosphorylation of Cyclin-dependent kinase 1 (CDK1).	[63]
BAICALEIN	DM4C7E6	Phase 2	BAICALEIN decreases the phosphorylation of Cyclin-dependent kinase 1 (CDK1).	[69]
GDC0941	DM1YAK6	Phase 2	GDC0941 decreases the phosphorylation of Cyclin-dependent kinase 1 (CDK1).	[70]
Salirasib	DMRSU4X	Phase 2	Salirasib decreases the phosphorylation of Cyclin-dependent kinase 1 (CDK1).	[75]
MK-1775	DM3WDZ5	Phase 2	MK-1775 decreases the phosphorylation of Cyclin-dependent kinase 1 (CDK1).	[77]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Cyclin-dependent kinase 1 (CDK1).	[81]
Steroid derivative 1	DMB0NVQ	Patented	Steroid derivative 1 decreases the phosphorylation of Cyclin-dependent kinase 1 (CDK1).	[87]

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