Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTASTJ3Q)

• DOT Name: Cyclin-dependent kinase inhibitor 1C (CDKN1C)
• Synonyms: Cyclin-dependent kinase inhibitor p57; p57Kip2
• Gene Name: CDKN1C
• Related Disease:
  Beckwith-Wiedemann syndrome
  IMAGe syndrome
  Rhabdomyosarcoma
  Beckwith-Wiedemann syndrome due to CDKN1C mutation
  Intrauterine growth restriction-short stature-early adult-onset diabetes syndrome
  Silver-Russell syndrome
• UniProt ID: CDN1C_HUMAN
• Pfam ID: PF02234
• Sequence:
  MSDASLRSTSTMERLVARGTFPVLVRTSACRSLFGPVDHEELSRELQARLAELNAEDQNR
  WDYDFQQDMPLRGPGRLQWTEVDSDSVPAFYRETVQVGRCRLLLAPRPVAVAVAVSPPLE
  PAAESLDGLEEAPEQLPSVPVPAPASTPPPVPVLAPAPAPAPAPVAAPVAAPVAVAVLAP
  APAPAPAPAPAPAPVAAPAPAPAPAPAPAPAPAPAPDAAPQESAEQGANQGQRGQEPLAD
  QLHSGISGRPAAGTAAASANGAAIKKLSGPLISDFFAKRKRSAPEKSSGDVPAPCPSPSA
  APGVGSVEQTPRKRLR
• Function: Potent tight-binding inhibitor of several G1 cyclin/CDK complexes (cyclin E-CDK2, cyclin D2-CDK4, and cyclin A-CDK2) and, to lesser extent, of the mitotic cyclin B-CDC2. Negative regulator of cell proliferation. May play a role in maintenance of the non-proliferative state throughout life.
• Tissue Specificity: Expressed in the heart, brain, lung, skeletal muscle, kidney, pancreas and testis. Expressed in the eye. High levels are seen in the placenta while low levels are seen in the liver.
• KEGG Pathway: Cell cycle (hsa04110)
• Reactome Pathway:
  Defective binding of RB1 mutants to E2F1,(E2F2, E2F3) (R-HSA-9661069)
  Cyclin D associated events in G1 (R-HSA-69231)

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Beckwith-Wiedemann syndrome	DISH15GR	Definitive	Autosomal dominant	[1]
IMAGe syndrome	DISOGW88	Definitive	Autosomal dominant	[2]
Rhabdomyosarcoma	DISNR7MS	Moderate	Autosomal dominant	[3]
Beckwith-Wiedemann syndrome due to CDKN1C mutation	DIS24U7V	Supportive	Autosomal dominant	[4]
Intrauterine growth restriction-short stature-early adult-onset diabetes syndrome	DIS50A4M	Supportive	Autosomal dominant	[5]
Silver-Russell syndrome	DISSVJ1D	Limited	Autosomal dominant	[1]

This DOT Affected the Drug Response of 4 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Temozolomide	DMKECZD	Approved	Cyclin-dependent kinase inhibitor 1C (CDKN1C) affects the response to substance of Temozolomide.	[45]
Fluorouracil	DMUM7HZ	Approved	Cyclin-dependent kinase inhibitor 1C (CDKN1C) affects the response to substance of Fluorouracil.	[46]
DTI-015	DMXZRW0	Approved	Cyclin-dependent kinase inhibitor 1C (CDKN1C) affects the response to substance of DTI-015.	[45]
Topotecan	DMP6G8T	Approved	Cyclin-dependent kinase inhibitor 1C (CDKN1C) affects the response to substance of Topotecan.	[47]

3 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 1C (CDKN1C).	[6]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Cyclin-dependent kinase inhibitor 1C (CDKN1C).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Cyclin-dependent kinase inhibitor 1C (CDKN1C).	[36]

43 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 inhibitor 1C (CDKN1C).	[7]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Cyclin-dependent kinase inhibitor 1C (CDKN1C).	[8]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Cyclin-dependent kinase inhibitor 1C (CDKN1C).	[9]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of Cyclin-dependent kinase inhibitor 1C (CDKN1C).	[10]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate affects the expression of Cyclin-dependent kinase inhibitor 1C (CDKN1C).	[11]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Cyclin-dependent kinase inhibitor 1C (CDKN1C).	[12]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Cyclin-dependent kinase inhibitor 1C (CDKN1C).	[13]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Cyclin-dependent kinase inhibitor 1C (CDKN1C).	[15]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Cyclin-dependent kinase inhibitor 1C (CDKN1C).	[16]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Cyclin-dependent kinase inhibitor 1C (CDKN1C).	[17]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Cyclin-dependent kinase inhibitor 1C (CDKN1C).	[18]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Cyclin-dependent kinase inhibitor 1C (CDKN1C).	[19]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Cyclin-dependent kinase inhibitor 1C (CDKN1C).	[20]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Cyclin-dependent kinase inhibitor 1C (CDKN1C).	[21]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Cyclin-dependent kinase inhibitor 1C (CDKN1C).	[16]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Cyclin-dependent kinase inhibitor 1C (CDKN1C).	[13]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Cyclin-dependent kinase inhibitor 1C (CDKN1C).	[8]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of Cyclin-dependent kinase inhibitor 1C (CDKN1C).	[22]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of Cyclin-dependent kinase inhibitor 1C (CDKN1C).	[23]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Cyclin-dependent kinase inhibitor 1C (CDKN1C).	[24]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of Cyclin-dependent kinase inhibitor 1C (CDKN1C).	[25]
Azacitidine	DMTA5OE	Approved	Azacitidine increases the expression of Cyclin-dependent kinase inhibitor 1C (CDKN1C).	[19]
Simvastatin	DM30SGU	Approved	Simvastatin increases the expression of Cyclin-dependent kinase inhibitor 1C (CDKN1C).	[26]
Alitretinoin	DMME8LH	Approved	Alitretinoin decreases the expression of Cyclin-dependent kinase inhibitor 1C (CDKN1C).	[8]
Berberine	DMC5Q8X	Phase 4	Berberine increases the expression of Cyclin-dependent kinase inhibitor 1C (CDKN1C).	[27]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Cyclin-dependent kinase inhibitor 1C (CDKN1C).	[28]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Cyclin-dependent kinase inhibitor 1C (CDKN1C).	[29]
DNCB	DMDTVYC	Phase 2	DNCB increases the expression of Cyclin-dependent kinase inhibitor 1C (CDKN1C).	[30]
GSK2110183	DMZHB37	Phase 2	GSK2110183 increases the expression of Cyclin-dependent kinase inhibitor 1C (CDKN1C).	[31]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Cyclin-dependent kinase inhibitor 1C (CDKN1C).	[32]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Cyclin-dependent kinase inhibitor 1C (CDKN1C).	[33]
PMID28870136-Compound-48	DMPIM9L	Patented	PMID28870136-Compound-48 increases the expression of Cyclin-dependent kinase inhibitor 1C (CDKN1C).	[34]
Harmine	DMPA5WD	Patented	Harmine decreases the expression of Cyclin-dependent kinase inhibitor 1C (CDKN1C).	[35]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Cyclin-dependent kinase inhibitor 1C (CDKN1C).	[17]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Cyclin-dependent kinase inhibitor 1C (CDKN1C).	[37]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Cyclin-dependent kinase inhibitor 1C (CDKN1C).	[38]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Cyclin-dependent kinase inhibitor 1C (CDKN1C).	[39]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Cyclin-dependent kinase inhibitor 1C (CDKN1C).	[40]
4-hydroxy-2-nonenal	DM2LJFZ	Investigative	4-hydroxy-2-nonenal decreases the expression of Cyclin-dependent kinase inhibitor 1C (CDKN1C).	[41]
Lithium chloride	DMHYLQ2	Investigative	Lithium chloride increases the expression of Cyclin-dependent kinase inhibitor 1C (CDKN1C).	[42]
all-trans-4-oxo-retinoic acid	DMM2R1N	Investigative	all-trans-4-oxo-retinoic acid increases the expression of Cyclin-dependent kinase inhibitor 1C (CDKN1C).	[8]
Linalool	DMGZQ5P	Investigative	Linalool increases the expression of Cyclin-dependent kinase inhibitor 1C (CDKN1C).	[43]
N-nonylphenol	DMH3OUX	Investigative	N-nonylphenol increases the expression of Cyclin-dependent kinase inhibitor 1C (CDKN1C).	[44]

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