Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTCLOV90)

DOT Name Cyclin-dependent kinase 4 inhibitor C (CDKN2C)
Synonyms Cyclin-dependent kinase 6 inhibitor; p18-INK4c; p18-INK6
Gene Name CDKN2C
UniProt ID
CDN2C_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
1BU9; 1G3N; 1IHB; 1MX2; 1MX4; 1MX6
Pfam ID
PF12796 ; PF13637
Sequence
MAEPWGNELASAAARGDLEQLTSLLQNNVNVNAQNGFGRTALQVMKLGNPEIARRLLLRG
ANPDLKDRTGFAVIHDAARAGFLDTLQTLLEFQADVNIEDNEGNLPLHLAAKEGHLRVVE
FLVKHTASNVGHRNHKGDTACDLARLYGRNEVVSLMQANGAGGATNLQ
Function Interacts strongly with CDK6, weakly with CDK4. Inhibits cell growth and proliferation with a correlated dependence on endogenous retinoblastoma protein RB.
Tissue Specificity Highest levels found in skeletal muscle. Also found in pancreas and heart.
KEGG Pathway
Endocrine resistance (hsa01522 )
Cell cycle (hsa04110 )
Cushing syndrome (hsa04934 )
Human T-cell leukemia virus 1 infection (hsa05166 )
Transcriptio.l misregulation in cancer (hsa05202 )
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 )
Oxidative Stress Induced Senescence (R-HSA-2559580 )

Molecular Interaction Atlas (MIA) of This DOT

Molecular Interaction Atlas (MIA) 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
Doxorubicin DMVP5YE Approved Cyclin-dependent kinase 4 inhibitor C (CDKN2C) affects the response to substance of Doxorubicin. [33]
Paclitaxel DMLB81S Approved Cyclin-dependent kinase 4 inhibitor C (CDKN2C) affects the response to substance of Paclitaxel. [33]
Vinblastine DM5TVS3 Approved Cyclin-dependent kinase 4 inhibitor C (CDKN2C) affects the response to substance of Vinblastine. [33]
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40 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the expression of Cyclin-dependent kinase 4 inhibitor C (CDKN2C). [1]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Cyclin-dependent kinase 4 inhibitor C (CDKN2C). [2]
Tretinoin DM49DUI Approved Tretinoin increases the expression of Cyclin-dependent kinase 4 inhibitor C (CDKN2C). [3]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Cyclin-dependent kinase 4 inhibitor C (CDKN2C). [4]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Cyclin-dependent kinase 4 inhibitor C (CDKN2C). [5]
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of Cyclin-dependent kinase 4 inhibitor C (CDKN2C). [6]
Estradiol DMUNTE3 Approved Estradiol decreases the expression of Cyclin-dependent kinase 4 inhibitor C (CDKN2C). [7]
Quercetin DM3NC4M Approved Quercetin decreases the expression of Cyclin-dependent kinase 4 inhibitor C (CDKN2C). [8]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide decreases the expression of Cyclin-dependent kinase 4 inhibitor C (CDKN2C). [9]
Calcitriol DM8ZVJ7 Approved Calcitriol decreases the expression of Cyclin-dependent kinase 4 inhibitor C (CDKN2C). [10]
Testosterone DM7HUNW Approved Testosterone decreases the expression of Cyclin-dependent kinase 4 inhibitor C (CDKN2C). [10]
Progesterone DMUY35B Approved Progesterone increases the expression of Cyclin-dependent kinase 4 inhibitor C (CDKN2C). [11]
Fluorouracil DMUM7HZ Approved Fluorouracil decreases the expression of Cyclin-dependent kinase 4 inhibitor C (CDKN2C). [12]
Dexamethasone DMMWZET Approved Dexamethasone increases the expression of Cyclin-dependent kinase 4 inhibitor C (CDKN2C). [13]
Demecolcine DMCZQGK Approved Demecolcine decreases the expression of Cyclin-dependent kinase 4 inhibitor C (CDKN2C). [14]
Cannabidiol DM0659E Approved Cannabidiol decreases the expression of Cyclin-dependent kinase 4 inhibitor C (CDKN2C). [15]
Troglitazone DM3VFPD Approved Troglitazone decreases the expression of Cyclin-dependent kinase 4 inhibitor C (CDKN2C). [16]
Bicalutamide DMZMSPF Approved Bicalutamide decreases the expression of Cyclin-dependent kinase 4 inhibitor C (CDKN2C). [17]
Isoflavone DM7U58J Phase 4 Isoflavone decreases the expression of Cyclin-dependent kinase 4 inhibitor C (CDKN2C). [18]
Chlorpromazine DMBGZI3 Phase 3 Trial Chlorpromazine decreases the expression of Cyclin-dependent kinase 4 inhibitor C (CDKN2C). [19]
Genistein DM0JETC Phase 2/3 Genistein decreases the expression of Cyclin-dependent kinase 4 inhibitor C (CDKN2C). [7]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of Cyclin-dependent kinase 4 inhibitor C (CDKN2C). [8]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of Cyclin-dependent kinase 4 inhibitor C (CDKN2C). [20]
Leflunomide DMR8ONJ Phase 1 Trial Leflunomide decreases the expression of Cyclin-dependent kinase 4 inhibitor C (CDKN2C). [21]
AMG 900 DMASGXJ Phase 1 AMG 900 increases the expression of Cyclin-dependent kinase 4 inhibitor C (CDKN2C). [22]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Cyclin-dependent kinase 4 inhibitor C (CDKN2C). [23]
Flavonoid derivative 1 DMCQP0B Patented Flavonoid derivative 1 decreases the expression of Cyclin-dependent kinase 4 inhibitor C (CDKN2C). [24]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of Cyclin-dependent kinase 4 inhibitor C (CDKN2C). [7]
Milchsaure DM462BT Investigative Milchsaure decreases the expression of Cyclin-dependent kinase 4 inhibitor C (CDKN2C). [25]
Coumestrol DM40TBU Investigative Coumestrol increases the expression of Cyclin-dependent kinase 4 inhibitor C (CDKN2C). [26]
Acetaldehyde DMJFKG4 Investigative Acetaldehyde decreases the expression of Cyclin-dependent kinase 4 inhibitor C (CDKN2C). [27]
geraniol DMS3CBD Investigative geraniol decreases the expression of Cyclin-dependent kinase 4 inhibitor C (CDKN2C). [28]
Phencyclidine DMQBEYX Investigative Phencyclidine decreases the expression of Cyclin-dependent kinase 4 inhibitor C (CDKN2C). [29]
Manganese DMKT129 Investigative Manganese decreases the expression of Cyclin-dependent kinase 4 inhibitor C (CDKN2C). [30]
U0126 DM31OGF Investigative U0126 increases the expression of Cyclin-dependent kinase 4 inhibitor C (CDKN2C). [31]
Chrysin DM7V2LG Investigative Chrysin decreases the expression of Cyclin-dependent kinase 4 inhibitor C (CDKN2C). [24]
Kaempferol DMHEMUB Investigative Kaempferol decreases the expression of Cyclin-dependent kinase 4 inhibitor C (CDKN2C). [24]
Linalool DMGZQ5P Investigative Linalool increases the expression of Cyclin-dependent kinase 4 inhibitor C (CDKN2C). [32]
Apigenin DMI3491 Investigative Apigenin increases the expression of Cyclin-dependent kinase 4 inhibitor C (CDKN2C). [24]
Myricetin DMTV4L0 Investigative Myricetin increases the expression of Cyclin-dependent kinase 4 inhibitor C (CDKN2C). [24]
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⏷ Show the Full List of 40 Drug(s)

References

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2 Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
3 Benzodithiophenes potentiate differentiation of acute promyelocytic leukemia cells by lowering the threshold for ligand-mediated corepressor/coactivator exchange with retinoic acid receptor alpha and enhancing changes in all-trans-retinoic acid-regulated gene expression. Cancer Res. 2005 Sep 1;65(17):7856-65. doi: 10.1158/0008-5472.CAN-05-1056.
4 Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
5 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
6 Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
7 Convergent transcriptional profiles induced by endogenous estrogen and distinct xenoestrogens in breast cancer cells. Carcinogenesis. 2006 Aug;27(8):1567-78.
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9 Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
10 Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
11 Coordinate up-regulation of TMEM97 and cholesterol biosynthesis genes in normal ovarian surface epithelial cells treated with progesterone: implications for pathogenesis of ovarian cancer. BMC Cancer. 2007 Dec 11;7:223.
12 Transcriptional profiling of MCF7 breast cancer cells in response to 5-Fluorouracil: relationship with cell cycle changes and apoptosis, and identification of novel targets of p53. Int J Cancer. 2006 Sep 1;119(5):1164-75.
13 Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
14 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
15 Cannabidiol enhances cytotoxicity of anti-cancer drugs in human head and neck squamous cell carcinoma. Sci Rep. 2020 Nov 26;10(1):20622. doi: 10.1038/s41598-020-77674-y.
16 Effects of ciglitazone and troglitazone on the proliferation of human stomach cancer cells. World J Gastroenterol. 2009 Jan 21;15(3):310-20.
17 Microarray analysis of bicalutamide action on telomerase activity, p53 pathway and viability of prostate carcinoma cell lines. J Pharm Pharmacol. 2005 Jan;57(1):83-92.
18 Soy isoflavones exert differential effects on androgen responsive genes in LNCaP human prostate cancer cells. J Nutr. 2007 Apr;137(4):964-72.
19 Effects of chlorpromazine with and without UV irradiation on gene expression of HepG2 cells. Mutat Res. 2005 Aug 4;575(1-2):47-60. doi: 10.1016/j.mrfmmm.2005.03.002. Epub 2005 Apr 26.
20 The BET bromodomain inhibitor JQ1 suppresses growth of pancreatic ductal adenocarcinoma in patient-derived xenograft models. Oncogene. 2016 Feb 18;35(7):833-45.
21 Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
22 AMG900 as novel inhibitor of the translationally controlled tumor protein. Chem Biol Interact. 2021 Jan 25;334:109349. doi: 10.1016/j.cbi.2020.109349. Epub 2020 Nov 28.
23 Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
24 Flavones and flavonols exert cytotoxic effects on a human oesophageal adenocarcinoma cell line (OE33) by causing G2/M arrest and inducing apoptosis. Food Chem Toxicol. 2008 Jun;46(6):2042-53. doi: 10.1016/j.fct.2008.01.049. Epub 2008 Feb 7.
25 Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
26 Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
27 Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.
28 Geraniol suppresses prostate cancer growth through down-regulation of E2F8. Cancer Med. 2016 Oct;5(10):2899-2908.
29 Differential response of Mono Mac 6, BEAS-2B, and Jurkat cells to indoor dust. Environ Health Perspect. 2007 Sep;115(9):1325-32.
30 Gene expression profiling of human primary astrocytes exposed to manganese chloride indicates selective effects on several functions of the cells. Neurotoxicology. 2007 May;28(3):478-89.
31 Pharmacologic inhibition of RAF-->MEK-->ERK signaling elicits pancreatic cancer cell cycle arrest through induced expression of p27Kip1. Cancer Res. 2005 Jun 1;65(11):4870-80. doi: 10.1158/0008-5472.CAN-04-2848.
32 Linalool Induces Cell Cycle Arrest and Apoptosis in Leukemia Cells and Cervical Cancer Cells through CDKIs. Int J Mol Sci. 2015 Nov 26;16(12):28169-79. doi: 10.3390/ijms161226089.
33 Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.