Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0IHDKL)

• DOT Name: Cell cycle progression protein 1 (CCPG1)
• Synonyms: Cell cycle progression restoration protein 8
• Gene Name: CCPG1
• UniProt ID: CCPG1_HUMAN
• PDB ID: 7D0E
• Sequence:
  MSENSSDSDSSCGWTVISHEGSDIEMLNSVTPTDSCEPAPECSSLEQEELQALQIEQGES
  SQNGTVLMEETAYPALEETSSTIEAEEQKIPEDSIYIGTASDDSDIVTLEPPKLEEIGNQ
  EVVIVEEAQSSEDFNMGSSSSSQYTFCQPETVFSSQPSDDESSSDETSNQPSPAFRRRRA
  RKKTVSASESEDRLVAEQETEPSKELSKRQFSSGLNKCVILALVIAISMGFGHFYGTIQI
  QKRQQLVRKIHEDELNDMKDYLSQCQQEQESFIDYKSLKENLARCWTLTEAEKMSFETQK
  TNLATENQYLRVSLEKEEKALSSLQEELNKLREQIRILEDKGTSTELVKENQKLKQHLEE
  EKQKKHSFLSQRETLLTEAKMLKRELERERLVTTALRGELQQLSGSQLHGKSDSPNVYTE
  KKEIAILRERLTELERKLTFEQQRSDLWERLYVEAKDQNGKQGTDGKKKGGRGSHRAKNK
  SKETFLGSVKETFDAMKNSTKEFVRHHKEKIKQAKEAVKENLKKFSDSVKSTFRHFKDTT
  KNIFDEKGNKRFGATKEAAEKPRTVFSDYLHPQYKAPTENHHNRGPTMQNDGRKEKPVHF
  KEFRKNTNSKKCSPGHDCRENSHSFRKACSGVFDCAQQESMSLFNTVVNPIRMDEFRQII
  QRYMLKELDTFCHWNELDQFINKFFLNGVFIHDQKLFTDFVNDVKDYLRNMKEYEVDNDG
  VFEKLDEYIYRHFFGHTFSPPYGPRSVYIKPCHYSSL
• Function: Acts as an assembly platform for Rho protein signaling complexes. Limits guanine nucleotide exchange activity of MCF2L toward RHOA, which results in an inhibition of both its transcriptional activation ability and its transforming activity. Does not inhibit activity of MCF2L toward CDC42, or activity of MCF2 toward either RHOA or CDC42. May be involved in cell cycle regulation.

Molecular Interaction Atlas (MIA) of This DOT

24 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 Cell cycle progression protein 1 (CCPG1).	[1]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Cell cycle progression protein 1 (CCPG1).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Cell cycle progression protein 1 (CCPG1).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Cell cycle progression protein 1 (CCPG1).	[4]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Cell cycle progression protein 1 (CCPG1).	[5]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Cell cycle progression protein 1 (CCPG1).	[6]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Cell cycle progression protein 1 (CCPG1).	[7]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of Cell cycle progression protein 1 (CCPG1).	[6]
Indomethacin	DMSC4A7	Approved	Indomethacin increases the expression of Cell cycle progression protein 1 (CCPG1).	[9]
Bicalutamide	DMZMSPF	Approved	Bicalutamide increases the expression of Cell cycle progression protein 1 (CCPG1).	[10]
Ampicillin	DMHWE7P	Approved	Ampicillin decreases the expression of Cell cycle progression protein 1 (CCPG1).	[5]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Cell cycle progression protein 1 (CCPG1).	[11]
Curcumin	DMQPH29	Phase 3	Curcumin increases the expression of Cell cycle progression protein 1 (CCPG1).	[12]
PEITC	DMOMN31	Phase 2	PEITC increases the expression of Cell cycle progression protein 1 (CCPG1).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Cell cycle progression protein 1 (CCPG1).	[14]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Cell cycle progression protein 1 (CCPG1).	[15]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Cell cycle progression protein 1 (CCPG1).	[16]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Cell cycle progression protein 1 (CCPG1).	[17]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Cell cycle progression protein 1 (CCPG1).	[18]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Cell cycle progression protein 1 (CCPG1).	[19]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Cell cycle progression protein 1 (CCPG1).	[20]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Cell cycle progression protein 1 (CCPG1).	[21]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Cell cycle progression protein 1 (CCPG1).	[22]
KOJIC ACID	DMP84CS	Investigative	KOJIC ACID decreases the expression of Cell cycle progression protein 1 (CCPG1).	[23]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Cell cycle progression protein 1 (CCPG1).	[8]

References

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• [3] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [6] Synergistic antiproliferative effect of arsenic trioxide combined with bortezomib in HL60 cell line and primary blasts from patients affected by myeloproliferative disorders. Cancer Genet Cytogenet. 2010 Jun;199(2):110-20. doi: 10.1016/j.cancergencyto.2010.02.010.
• [7] 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.
• [8] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [9] Anti-inflammatory agent indomethacin reduces invasion and alters metabolism in a human breast cancer cell line. Neoplasia. 2007 Mar;9(3):222-35.
• [10] 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.
• [11] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [12] Gene-expression profiling during curcumin-induced apoptosis reveals downregulation of CXCR4. Exp Hematol. 2007 Jan;35(1):84-95.
• [13] Phenethyl isothiocyanate alters the gene expression and the levels of protein associated with cell cycle regulation in human glioblastoma GBM 8401 cells. Environ Toxicol. 2017 Jan;32(1):176-187.
• [14] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [15] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [16] 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.
• [17] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [18] Bisphenolic compounds alter gene expression in MCF-7 cells through interaction with estrogen receptor . Toxicol Appl Pharmacol. 2020 Jul 15;399:115030. doi: 10.1016/j.taap.2020.115030. Epub 2020 May 6.
• [19] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [20] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [21] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [22] Sulforaphane-induced apoptosis in human leukemia HL-60 cells through extrinsic and intrinsic signal pathways and altering associated genes expression assayed by cDNA microarray. Environ Toxicol. 2017 Jan;32(1):311-328.
• [23] Toxicogenomics of kojic acid on gene expression profiling of a375 human malignant melanoma cells. Biol Pharm Bull. 2006 Apr;29(4):655-69.