Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRLOZ4Y)

• DOT Name: Palmdelphin (PALMD)
• Synonyms: Paralemmin-like protein
• Gene Name: PALMD
• UniProt ID: PALMD_HUMAN
• Pfam ID: PF03285
• Sequence:
  MEEAELVKGRLQAITDKRKIQEEISQKRLKIEEDKLKHQHLKKKALREKWLLDGISSGKE
  QEEMKKQNQQDQHQIQVLEQSILRLEKEIQDLEKAELQISTKEEAILKKLKSIERTTEDI
  IRSVKVEREERAEESIEDIYANIPDLPKSYIPSRLRKEINEEKEDDEQNRKALYAMEIKV
  EKDLKTGESTVLSSIPLPSDDFKGTGIKVYDDGQKSVYAVSSNHSAAYNGTDGLAPVEVE
  ELLRQASERNSKSPTEYHEPVYANPFYRPTTPQRETVTPGPNFQERIKIKTNGLGIGVNE
  SIHNMGNGLSEERGNNFNHISPIPPVPHPRSVIQQAEEKLHTPQKRLMTPWEESNVMQDK
  DAPSPKPRLSPRETIFGKSEHQNSSPTCQEDEEDVRYNIVHSLPPDINDTEPVTMIFMGY
  QQAEDSEEDKKFLTGYDGIIHAELVVIDDEEEEDEGEAEKPSYHPIAPHSQVYQPAKPTP
  LPRKRSEASPHENTNHKSPHKNSISLKEQEESLGSPVHHSPFDAQTTGDGTEDPSLTALR
  MRMAKLGKKVI
• Tissue Specificity: Ubiquitous. Most abundant in cardiac and skeletal muscle.

Molecular Interaction Atlas (MIA) of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Palmdelphin (PALMD).	[1]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of Palmdelphin (PALMD).	[18]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Palmdelphin (PALMD).	[19]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Palmdelphin (PALMD).	[19]

19 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 Palmdelphin (PALMD).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Palmdelphin (PALMD).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Palmdelphin (PALMD).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Palmdelphin (PALMD).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Palmdelphin (PALMD).	[6]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Palmdelphin (PALMD).	[7]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Palmdelphin (PALMD).	[8]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Palmdelphin (PALMD).	[9]
Phenobarbital	DMXZOCG	Approved	Phenobarbital decreases the expression of Palmdelphin (PALMD).	[10]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of Palmdelphin (PALMD).	[11]
Malathion	DMXZ84M	Approved	Malathion decreases the expression of Palmdelphin (PALMD).	[12]
Ethinyl estradiol	DMODJ40	Approved	Ethinyl estradiol decreases the expression of Palmdelphin (PALMD).	[13]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Palmdelphin (PALMD).	[14]
Genistein	DM0JETC	Phase 2/3	Genistein affects the expression of Palmdelphin (PALMD).	[15]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Palmdelphin (PALMD).	[16]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Palmdelphin (PALMD).	[17]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Palmdelphin (PALMD).	[20]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Palmdelphin (PALMD).	[21]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Palmdelphin (PALMD).	[22]

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] 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] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [4] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [7] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [8] 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.
• [9] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [10] Proteomic analysis of hepatic effects of phenobarbital in mice with humanized liver. Arch Toxicol. 2022 Oct;96(10):2739-2754. doi: 10.1007/s00204-022-03338-7. Epub 2022 Jul 26.
• [11] Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
• [12] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [13] The genomic response of a human uterine endometrial adenocarcinoma cell line to 17alpha-ethynyl estradiol. Toxicol Sci. 2009 Jan;107(1):40-55.
• [14] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [15] Dose- and time-dependent transcriptional response of Ishikawa cells exposed to genistein. Toxicol Sci. 2016 May;151(1):71-87.
• [16] Gene expression profiling of A549 cells exposed to Milan PM2.5. Toxicol Lett. 2012 Mar 7;209(2):136-45.
• [17] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [18] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [19] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [20] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.
• [21] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [22] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.