Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2GP6RL)

• DOT Name: Cyclin-dependent kinase 3 (CDK3)
• Synonyms: EC 2.7.11.22; Cell division protein kinase 3
• Gene Name: CDK3
• UniProt ID: CDK3_HUMAN
• PDB ID: 7XQK; 8H4R
• EC Number: 2.7.11.22
• Pfam ID: PF00069
• Sequence:
  MDMFQKVEKIGEGTYGVVYKAKNRETGQLVALKKIRLDLEMEGVPSTAIREISLLKELKH
  PNIVRLLDVVHNERKLYLVFEFLSQDLKKYMDSTPGSELPLHLIKSYLFQLLQGVSFCHS
  HRVIHRDLKPQNLLINELGAIKLADFGLARAFGVPLRTYTHEVVTLWYRAPEILLGSKFY
  TTAVDIWSIGCIFAEMVTRKALFPGDSEIDQLFRIFRMLGTPSEDTWPGVTQLPDYKGSF
  PKWTRKGLEEIVPNLEPEGRDLLMQLLQYDPSQRITAKTALAHPYFSSPEPSPAARQYVL
  QRFRH
• Function: Serine/threonine-protein kinase that plays a critical role in the control of the eukaryotic cell cycle; involved in G0-G1 and G1-S cell cycle transitions. Interacts with CCNC/cyclin-C during interphase. Phosphorylates histone H1, ATF1, RB1 and CABLES1. ATF1 phosphorylation triggers ATF1 transactivation and transcriptional activities, and promotes cell proliferation and transformation. CDK3/cyclin-C mediated RB1 phosphorylation is required for G0-G1 transition. Promotes G1-S transition probably by contributing to the activation of E2F1, E2F2 and E2F3 in a RB1-independent manner.
• Tissue Specificity: Expressed in cancer cell lines and glioblastoma tissue.

Molecular Interaction Atlas (MIA) of This DOT

2 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 3 (CDK3).	[1]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Cyclin-dependent kinase 3 (CDK3).	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Cyclin-dependent kinase 3 (CDK3).	[2]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Cyclin-dependent kinase 3 (CDK3).	[4]
Aspirin	DM672AH	Approved	Aspirin increases the expression of Cyclin-dependent kinase 3 (CDK3).	[5]
Sulindac	DM2QHZU	Approved	Sulindac decreases the expression of Cyclin-dependent kinase 3 (CDK3).	[5]
Ritonavir	DMU764S	Approved	Ritonavir increases the expression of Cyclin-dependent kinase 3 (CDK3).	[6]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Cyclin-dependent kinase 3 (CDK3).	[4]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of Cyclin-dependent kinase 3 (CDK3).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Cyclin-dependent kinase 3 (CDK3).	[7]
Scriptaid	DM9JZ21	Preclinical	Scriptaid affects the expression of Cyclin-dependent kinase 3 (CDK3).	[8]

References

• [1] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [2] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [3] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [4] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [5] Expression profile analysis of colon cancer cells in response to sulindac or aspirin. Biochem Biophys Res Commun. 2002 Mar 29;292(2):498-512.
• [6] Ritonavir blocks AKT signaling, activates apoptosis and inhibits migration and invasion in ovarian cancer cells. Mol Cancer. 2009 Apr 22;8:26. doi: 10.1186/1476-4598-8-26.
• [7] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [8] Histone deacetylase inhibitor scriptaid induces cell cycle arrest and epigenetic change in colon cancer cells. Int J Oncol. 2008 Oct;33(4):767-76.