Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2QIDCL)

• DOT Name: LIM and SH3 domain protein 1 (LASP1)
• Synonyms: LASP-1; Metastatic lymph node gene 50 protein; MLN 50
• Gene Name: LASP1
• UniProt ID: LASP1_HUMAN
• PDB ID: 3I35
• Pfam ID: PF00412 ; PF00880 ; PF14604
• Sequence:
  MNPNCARCGKIVYPTEKVNCLDKFWHKACFHCETCKMTLNMKNYKGYEKKPYCNAHYPKQ
  SFTMVADTPENLRLKQQSELQSQVRYKEEFEKNKGKGFSVVADTPELQRIKKTQDQISNI
  KYHEEFEKSRMGPSGGEGMEPERRDSQDGSSYRRPLEQQQPHHIPTSAPVYQQPQQQPVA
  QSYGGYKEPAAPVSIQRSAPGGGGKRYRAVYDYSAADEDEVSFQDGDTIVNVQQIDDGWM
  YGTVERTGDTGMLPANYVEAI
• Function: Plays an important role in the regulation of dynamic actin-based, cytoskeletal activities. Agonist-dependent changes in LASP1 phosphorylation may also serve to regulate actin-associated ion transport activities, not only in the parietal cell but also in certain other F-actin-rich secretory epithelial cell types.

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Fluorouracil	DMUM7HZ	Approved	LIM and SH3 domain protein 1 (LASP1) affects the response to substance of Fluorouracil.	[19]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of LIM and SH3 domain protein 1 (LASP1).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of LIM and SH3 domain protein 1 (LASP1).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of LIM and SH3 domain protein 1 (LASP1).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of LIM and SH3 domain protein 1 (LASP1).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of LIM and SH3 domain protein 1 (LASP1).	[5]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of LIM and SH3 domain protein 1 (LASP1).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of LIM and SH3 domain protein 1 (LASP1).	[7]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of LIM and SH3 domain protein 1 (LASP1).	[8]
Hydroquinone	DM6AVR4	Approved	Hydroquinone affects the expression of LIM and SH3 domain protein 1 (LASP1).	[10]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone affects the expression of LIM and SH3 domain protein 1 (LASP1).	[11]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene increases the expression of LIM and SH3 domain protein 1 (LASP1).	[2]
Afimoxifene	DMFORDT	Phase 2	Afimoxifene increases the expression of LIM and SH3 domain protein 1 (LASP1).	[12]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of LIM and SH3 domain protein 1 (LASP1).	[14]
Pifithrin-alpha	DM63OD7	Terminated	Pifithrin-alpha increases the expression of LIM and SH3 domain protein 1 (LASP1).	[16]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of LIM and SH3 domain protein 1 (LASP1).	[17]
chloropicrin	DMSGBQA	Investigative	chloropicrin affects the expression of LIM and SH3 domain protein 1 (LASP1).	[18]

4 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 LIM and SH3 domain protein 1 (LASP1).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of LIM and SH3 domain protein 1 (LASP1).	[13]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of LIM and SH3 domain protein 1 (LASP1).	[15]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of LIM and SH3 domain protein 1 (LASP1).	[15]

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] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [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] Identification of novel low-dose bisphenol a targets in human foreskin fibroblast cells derived from hypospadias patients. PLoS One. 2012;7(5):e36711. doi: 10.1371/journal.pone.0036711. Epub 2012 May 4.
• [7] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [8] Proteomic analysis revealed association of aberrant ROS signaling with suberoylanilide hydroxamic acid-induced autophagy in Jurkat T-leukemia cells. Autophagy. 2010 Aug;6(6):711-24. doi: 10.4161/auto.6.6.12397. Epub 2010 Aug 17.
• [9] 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.
• [10] Proteomic analysis to identify the cellular responses induced by hydroquinone in human embryonic lung fibroblasts. Toxicol Mech Methods. 2006;16(1):1-6. doi: 10.1080/15376520500191797.
• [11] Proteomic analysis of human adipose tissue after rosiglitazone treatment shows coordinated changes to promote glucose uptake. Obesity (Silver Spring). 2010 Jan;18(1):27-34. doi: 10.1038/oby.2009.208. Epub 2009 Jun 25.
• [12] Gene expression preferentially regulated by tamoxifen in breast cancer cells and correlations with clinical outcome. Cancer Res. 2006 Jul 15;66(14):7334-40.
• [13] Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
• [14] 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.
• [15] 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.
• [16] Long non-coding RNA LINC00672 contributes to p53 protein-mediated gene suppression and promotes endometrial cancer chemosensitivity. J Biol Chem. 2017 Apr 7;292(14):5801-5813. doi: 10.1074/jbc.M116.758508. Epub 2017 Feb 23.
• [17] Proteomics and disease network associations evaluation of environmentally relevant Bisphenol A concentrations in a human 3D neural stem cell model. Front Cell Dev Biol. 2023 Aug 16;11:1236243. doi: 10.3389/fcell.2023.1236243. eCollection 2023.
• [18] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [19] 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.