Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQOOUC4)

• DOT Name: Transforming growth factor beta receptor type 3 (TGFBR3)
• Synonyms: TGF-beta receptor type 3; TGFR-3; Betaglycan; Transforming growth factor beta receptor III; TGF-beta receptor type III
• Gene Name: TGFBR3
• Related Disease:
  Behcet disease
  Ovarian neoplasm
  Adenocarcinoma
  Asthma
  Bladder cancer
  Breast cancer
  Breast carcinoma
  Clear cell renal carcinoma
  Colon cancer
  Colon carcinoma
  Depression
  Knee osteoarthritis
  Lung cancer
  Lung carcinoma
  Neuroblastoma
  Non-hodgkin lymphoma
  Non-insulin dependent diabetes
  Non-small-cell lung cancer
  OPTN-related open angle glaucoma
  Osteoarthritis
  Pancreatic tumour
  Prostate cancer
  Prostate carcinoma
  Prostate neoplasm
  Renal cell carcinoma
  Squamous cell carcinoma
  Triple negative breast cancer
  Urinary bladder cancer
  Urinary bladder neoplasm
  Advanced cancer
  Chronic obstructive pulmonary disease
  Bone osteosarcoma
  Endometrial cancer
  Endometrial carcinoma
  Female hypogonadism
  Glaucoma/ocular hypertension
  High blood pressure
  Malignant soft tissue neoplasm
  Matthew-Wood syndrome
  Myocardial infarction
  Osteosarcoma
  Pancreatic ductal carcinoma
  Sarcoma
  Stroke
• UniProt ID: TGBR3_HUMAN
• PDB ID: 7LBG
• Pfam ID: PF00100
• Sequence:
  MTSHYVIAIFALMSSCLATAGPEPGALCELSPVSASHPVQALMESFTVLSGCASRGTTGL
  PQEVHVLNLRTAGQGPGQLQREVTLHLNPISSVHIHHKSVVFLLNSPHPLVWHLKTERLA
  TGVSRLFLVSEGSVVQFSSANFSLTAETEERNFPHGNEHLLNWARKEYGAVTSFTELKIA
  RNIYIKVGEDQVFPPKCNIGKNFLSLNYLAEYLQPKAAEGCVMSSQPQNEEVHIIELITP
  NSNPYSAFQVDITIDIRPSQEDLEVVKNLILILKCKKSVNWVIKSFDVKGSLKIIAPNSI
  GFGKESERSMTMTKSIRDDIPSTQGNLVKWALDNGYSPITSYTMAPVANRFHLRLENNAE
  EMGDEEVHTIPPELRILLDPGALPALQNPPIRGGEGQNGGLPFPFPDISRRVWNEEGEDG
  LPRPKDPVIPSIQLFPGLREPEEVQGSVDIALSVKCDNEKMIVAVEKDSFQASGYSGMDV
  TLLDPTCKAKMNGTHFVLESPLNGCGTRPRWSALDGVVYYNSIVIQVPALGDSSGWPDGY
  EDLESGDNGFPGDMDEGDASLFTRPEIVVFNCSLQQVRNPSSFQEQPHGNITFNMELYNT
  DLFLVPSQGVFSVPENGHVYVEVSVTKAEQELGFAIQTCFISPYSNPDRMSHYTIIENIC
  PKDESVKFYSPKRVHFPIPQADMDKKRFSFVFKPVFNTSLLFLQCELTLCTKMEKHPQKL
  PKCVPPDEACTSLDASIIWAMMQNKKTFTKPLAVIHHEAESKEKGPSMKEPNPISPPIFH
  GLDTLTVMGIAFAAFVIGALLTGALWYIYSHTGETAGRQQVPTSPPASENSSAAHSIGST
  QSTPCSSSSTA
• Function: Binds to TGF-beta. Could be involved in capturing and retaining TGF-beta for presentation to the signaling receptors. In gonadotrope cells, acts as an inhibin A coreceptor and regulates follicle-stimulating hormone (FSH) levels and female fertility.
• Reactome Pathway:
  FGFR1b ligand binding and activation (R-HSA-190370)
  FGFR1c ligand binding and activation (R-HSA-190373)
  Signaling by BMP (R-HSA-201451)
  TGF-beta receptor signaling activates SMADs (R-HSA-2173789)
  Signaling by Activin (R-HSA-1502540)

Molecular Interaction Atlas (MIA) of This DOT

44 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Behcet disease	DISSYMBS	Definitive	Genetic Variation	[1]
Ovarian neoplasm	DISEAFTY	Definitive	Altered Expression	[2]
Adenocarcinoma	DIS3IHTY	Strong	Altered Expression	[3]
Asthma	DISW9QNS	Strong	Biomarker	[4]
Bladder cancer	DISUHNM0	Strong	Biomarker	[5]
Breast cancer	DIS7DPX1	Strong	Biomarker	[6]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[6]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[7]
Colon cancer	DISVC52G	Strong	Biomarker	[8]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[8]
Depression	DIS3XJ69	Strong	Genetic Variation	[9]
Knee osteoarthritis	DISLSNBJ	Strong	Genetic Variation	[10]
Lung cancer	DISCM4YA	Strong	Biomarker	[11]
Lung carcinoma	DISTR26C	Strong	Biomarker	[11]
Neuroblastoma	DISVZBI4	Strong	Biomarker	[12]
Non-hodgkin lymphoma	DISS2Y8A	Strong	Altered Expression	[13]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Genetic Variation	[14]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[15]
OPTN-related open angle glaucoma	DISDR98A	Strong	Genetic Variation	[16]
Osteoarthritis	DIS05URM	Strong	Altered Expression	[17]
Pancreatic tumour	DIS3U0LK	Strong	Biomarker	[18]
Prostate cancer	DISF190Y	Strong	Altered Expression	[19]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[19]
Prostate neoplasm	DISHDKGQ	Strong	Altered Expression	[19]
Renal cell carcinoma	DISQZ2X8	Strong	Altered Expression	[20]
Squamous cell carcinoma	DISQVIFL	Strong	Biomarker	[21]
Triple negative breast cancer	DISAMG6N	Strong	Biomarker	[22]
Urinary bladder cancer	DISDV4T7	Strong	Biomarker	[5]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[5]
Advanced cancer	DISAT1Z9	moderate	Biomarker	[23]
Chronic obstructive pulmonary disease	DISQCIRF	moderate	Biomarker	[24]
Bone osteosarcoma	DIST1004	Limited	Altered Expression	[25]
Endometrial cancer	DISW0LMR	Limited	Genetic Variation	[23]
Endometrial carcinoma	DISXR5CY	Limited	Genetic Variation	[23]
Female hypogonadism	DISWASB4	Limited	Genetic Variation	[26]
Glaucoma/ocular hypertension	DISLBXBY	Limited	Biomarker	[27]
High blood pressure	DISY2OHH	Limited	Altered Expression	[28]
Malignant soft tissue neoplasm	DISTC6NO	Limited	Biomarker	[29]
Matthew-Wood syndrome	DISA7HR7	Limited	Biomarker	[30]
Myocardial infarction	DIS655KI	Limited	Biomarker	[31]
Osteosarcoma	DISLQ7E2	Limited	Altered Expression	[25]
Pancreatic ductal carcinoma	DIS26F9Q	Limited	Biomarker	[30]
Sarcoma	DISZDG3U	Limited	Biomarker	[29]
Stroke	DISX6UHX	Limited	Genetic Variation	[32]

24 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 Transforming growth factor beta receptor type 3 (TGFBR3).	[33]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Transforming growth factor beta receptor type 3 (TGFBR3).	[34]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Transforming growth factor beta receptor type 3 (TGFBR3).	[35]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Transforming growth factor beta receptor type 3 (TGFBR3).	[36]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Transforming growth factor beta receptor type 3 (TGFBR3).	[37]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Transforming growth factor beta receptor type 3 (TGFBR3).	[38]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Transforming growth factor beta receptor type 3 (TGFBR3).	[39]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Transforming growth factor beta receptor type 3 (TGFBR3).	[40]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Transforming growth factor beta receptor type 3 (TGFBR3).	[41]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Transforming growth factor beta receptor type 3 (TGFBR3).	[42]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Transforming growth factor beta receptor type 3 (TGFBR3).	[43]
Niclosamide	DMJAGXQ	Approved	Niclosamide decreases the expression of Transforming growth factor beta receptor type 3 (TGFBR3).	[44]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of Transforming growth factor beta receptor type 3 (TGFBR3).	[45]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Transforming growth factor beta receptor type 3 (TGFBR3).	[46]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Transforming growth factor beta receptor type 3 (TGFBR3).	[47]
Acocantherin	DM7JT24	Approved	Acocantherin increases the expression of Transforming growth factor beta receptor type 3 (TGFBR3).	[48]
Diazepam	DM08E9O	Approved	Diazepam decreases the expression of Transforming growth factor beta receptor type 3 (TGFBR3).	[49]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Transforming growth factor beta receptor type 3 (TGFBR3).	[50]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Transforming growth factor beta receptor type 3 (TGFBR3).	[34]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Transforming growth factor beta receptor type 3 (TGFBR3).	[51]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Transforming growth factor beta receptor type 3 (TGFBR3).	[52]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Transforming growth factor beta receptor type 3 (TGFBR3).	[53]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Transforming growth factor beta receptor type 3 (TGFBR3).	[55]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Transforming growth factor beta receptor type 3 (TGFBR3).	[56]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the methylation of Transforming growth factor beta receptor type 3 (TGFBR3).	[54]

References

• [1] Association analysis of TGFBR3 gene with Behet's disease and idiopathic intermediate uveitis in a Caucasian population.Br J Ophthalmol. 2015 May;99(5):696-9. doi: 10.1136/bjophthalmol-2014-306198. Epub 2015 Feb 12.
• [2] Expression of betaglycan, an inhibin coreceptor, in normal human ovaries and ovarian sex cord-stromal tumors and its regulation in cultured human granulosa-luteal cells.J Clin Endocrinol Metab. 2003 Oct;88(10):5002-8. doi: 10.1210/jc.2003-030704.
• [3] Genomic alterations of ground-glass nodular lung adenocarcinoma.Sci Rep. 2018 May 16;8(1):7691. doi: 10.1038/s41598-018-25800-2.
• [4] Association between genetic variations of the transforming growth factor receptor type III and asthma in a Korean population.Exp Mol Med. 2010 Jun 30;42(6):420-7. doi: 10.3858/emm.2010.42.6.043.
• [5] Dual role of TGFBR3 in bladder cancer.Oncol Rep. 2013 Sep;30(3):1301-8. doi: 10.3892/or.2013.2599. Epub 2013 Jul 8.
• [6] The influence of genetic ancestry and ethnicity on breast cancer survival associated with genetic variation in the TGF--signaling pathway: The Breast Cancer Health Disparities Study.Cancer Causes Control. 2014 Mar;25(3):293-307. doi: 10.1007/s10552-013-0331-9. Epub 2013 Dec 12.
• [7] Decreased TGFBR3/betaglycan expression enhances the metastatic abilities of renal cell carcinoma cells through TGF--dependent and -independent mechanisms.Oncogene. 2018 Apr;37(16):2197-2212. doi: 10.1038/s41388-017-0084-0. Epub 2018 Feb 2.
• [8] Oncogenic Ki-ras confers a more aggressive colon cancer phenotype through modification of transforming growth factor-beta receptor III.J Biol Chem. 2001 Jan 12;276(2):1555-63. doi: 10.1074/jbc.M004553200.
• [9] Convergent animal and human evidence suggests the activin/inhibin pathway to be involved in antidepressant response.Transl Psychiatry. 2012 Oct 23;2(10):e177. doi: 10.1038/tp.2012.104.
• [10] Genome-wide analyses using UK Biobank data provide insights into the genetic architecture of osteoarthritis.Nat Genet. 2018 Apr;50(4):549-558. doi: 10.1038/s41588-018-0079-y. Epub 2018 Mar 20.
• [11] Upregulated lncRNA ADAMTS9-AS2 suppresses progression of lung cancer through inhibition of miR-223-3p and promotion of TGFBR3.IUBMB Life. 2018 Jun;70(6):536-546. doi: 10.1002/iub.1752. Epub 2018 Apr 29.
• [12] Type III TGF- receptor promotes FGF2-mediated neuronal differentiation in neuroblastoma.J Clin Invest. 2013 Nov;123(11):4786-98. doi: 10.1172/JCI69657.
• [13] Expression of TGF beta1 genes and their receptor types I, II, and III in low- and high-grade malignancy non-Hodgkin's lymphomas.Med Sci Monit. 2004 Jan;10(1):CR33-7.
• [14] Genetic Variants in HSD17B3, SMAD3, and IPO11 Impact Circulating Lipids in Response to Fenofibrate in Individuals With Type 2 Diabetes.Clin Pharmacol Ther. 2018 Apr;103(4):712-721. doi: 10.1002/cpt.798. Epub 2017 Nov 3.
• [15] HMGA2 functions as a competing endogenous RNA to promote lung cancer progression.Nature. 2014 Jan 9;505(7482):212-7. doi: 10.1038/nature12785. Epub 2013 Dec 4.
• [16] A common variant near TGFBR3 is associated with primary open angle glaucoma.Hum Mol Genet. 2015 Jul 1;24(13):3880-92. doi: 10.1093/hmg/ddv128. Epub 2015 Apr 10.
• [17] Abnormal transforming growth factor-beta expression in mesenchymal stem cells from patients with osteoarthritis.J Rheumatol. 2008 May;35(5):904-6. Epub 2008 Apr 1.
• [18] Loss of type III transforming growth factor beta receptor expression increases motility and invasiveness associated with epithelial to mesenchymal transition during pancreatic cancer progression.Carcinogenesis. 2008 Feb;29(2):252-62. doi: 10.1093/carcin/bgm249. Epub 2007 Nov 13.
• [19] TGFBR3 loss and consequences in prostate cancer.Prostate. 2007 Feb 15;67(3):301-11. doi: 10.1002/pros.20526.
• [20] Genomic profiling identifies alterations in TGFbeta signaling through loss of TGFbeta receptor expression in human renal cell carcinogenesis and progression.Oncogene. 2003 Sep 11;22(39):8053-62. doi: 10.1038/sj.onc.1206835.
• [21] Loss of GDF10/BMP3b as a prognostic marker collaborates with TGFBR3 to enhance chemotherapy resistance and epithelial-mesenchymal transition in oral squamous cell carcinoma.Mol Carcinog. 2016 May;55(5):499-513. doi: 10.1002/mc.22297. Epub 2015 Mar 1.
• [22] Transforming growth factor beta receptor type III is a tumor promoter in mesenchymal-stem like triple negative breast cancer.Breast Cancer Res. 2014 Jul 1;16(4):R69. doi: 10.1186/bcr3684.
• [23] Significance of TGFBR3 allelic loss in the deregulation of TGF signaling in primary human endometrial carcinomas.Oncol Rep. 2016 Feb;35(2):932-8. doi: 10.3892/or.2015.4400. Epub 2015 Nov 5.
• [24] Transforming growth factor-beta receptor-3 is associated with pulmonary emphysema.Am J Respir Cell Mol Biol. 2009 Sep;41(3):324-31. doi: 10.1165/rcmb.2008-0427OC. Epub 2009 Jan 8.
• [25] Deep RNA sequencing reveals the dynamic regulation of miRNA, lncRNAs, and mRNAs in osteosarcoma tumorigenesis and pulmonary metastasis.Cell Death Dis. 2018 Jul 10;9(7):772. doi: 10.1038/s41419-018-0813-5.
• [26] Haplotype and mutation analysis of the TGFBR3 gene in Chinese women with idiopathic premature ovarian failure.Gynecol Endocrinol. 2012 Jan;28(1):63-7. doi: 10.3109/09513590.2011.583954. Epub 2011 Jul 14.
• [27] Common genetic variants associated with open-angle glaucoma.Hum Mol Genet. 2011 Jun 15;20(12):2464-71. doi: 10.1093/hmg/ddr120. Epub 2011 Mar 22.
• [28] Expression of TGF-beta1 and its receptor genes (TbetaR I, TbetaR II, and TbetaR III-betaglycan) in peripheral blood leucocytes in patients with idiopathic pulmonary arterial hypertension and Eisenmenger's syndrome.Int J Mol Med. 2008 Jan;21(1):99-107.
• [29] TGFBR3 and MGEA5 rearrangements are much more common in "hybrid" hemosiderotic fibrolipomatous tumor-myxoinflammatory fibroblastic sarcomas than in classical myxoinflammatory fibroblastic sarcomas: a morphological and fluorescence in situ hybridization study.Hum Pathol. 2016 Jul;53:14-24. doi: 10.1016/j.humpath.2016.02.005. Epub 2016 Mar 2.
• [30] Macrophage-derived exosomal microRNA-501-3p promotes progression of pancreatic ductal adenocarcinoma through the TGFBR3-mediated TGF- signaling pathway.J Exp Clin Cancer Res. 2019 Jul 15;38(1):310. doi: 10.1186/s13046-019-1313-x.
• [31] MicroRNA let-7-TGFBR3 signalling regulates cardiomyocyte apoptosis after infarction.EBioMedicine. 2019 Aug;46:236-247. doi: 10.1016/j.ebiom.2019.08.001. Epub 2019 Aug 7.
• [32] Genetic predictors for stroke in children with sickle cell anemia.Blood. 2011 Jun 16;117(24):6681-4. doi: 10.1182/blood-2011-01-332205. Epub 2011 Apr 22.
• [33] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [34] 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.
• [35] 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.
• [36] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [37] 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.
• [38] 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.
• [39] 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.
• [40] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [41] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [42] 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.
• [43] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [44] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [45] 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.
• [46] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [47] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [48] Ouabain impairs cell migration, and invasion and alters gene expression of human osteosarcoma U-2 OS cells. Environ Toxicol. 2017 Nov;32(11):2400-2413. doi: 10.1002/tox.22453. Epub 2017 Aug 10.
• [49] Patterns of some extracellular matrix gene expression are similar in cells from cleft lip-palate patients and in human palatal fibroblasts exposed to diazepam in culture. Toxicology. 2009 Mar 4;257(1-2):10-6. doi: 10.1016/j.tox.2008.12.002. Epub 2008 Dec 9.
• [50] A high concentration of genistein down-regulates activin A, Smad3 and other TGF-beta pathway genes in human uterine leiomyoma cells. Exp Mol Med. 2012 Apr 30;44(4):281-92.
• [51] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [52] 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.
• [53] Chemical stresses fail to mimic the unfolded protein response resulting from luminal load with unfolded polypeptides. J Biol Chem. 2018 Apr 13;293(15):5600-5612.
• [54] 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.
• [55] 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.
• [56] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.