Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6VY3A3)

• DOT Name: Spectrin alpha chain, non-erythrocytic 1 (SPTAN1)
• Synonyms: Alpha-II spectrin; Fodrin alpha chain; Spectrin, non-erythroid alpha subunit
• Gene Name: SPTAN1
• Related Disease:
  Developmental and epileptic encephalopathy, 5
  Epilepsy
  Infantile spasm
  Acute erythroid leukemia
  Adult T-cell leukemia/lymphoma
  Advanced cancer
  Autoimmune disease
  Cardiac failure
  Childhood epilepsy with centrotemporal spikes
  Colon cancer
  Colon carcinoma
  Congestive heart failure
  Early myoclonic encephalopathy
  Fanconi anemia complementation group A
  Fanconi's anemia
  Gastric cancer
  Infantile epileptic-dyskinetic encephalopathy
  Migraine disorder
  Migraine with aura
  Moyamoya disease
  Myopathy
  Nervous system disease
  Refractory chronic myeloid leukaemia
  Sjogren syndrome
  Stomach cancer
  Systemic lupus erythematosus
  T-cell leukaemia
  Vascular purpura
  Isolated congenital microcephaly
  West syndrome
  Subarachnoid hemorrhage
  Tuberculosis
  Colorectal carcinoma
  Intellectual disability
  Neoplasm
• UniProt ID: SPTN1_HUMAN
• PDB ID: 2FOT; 3F31; 3FB2; 5FW9; 5FWB; 5FWC; 6ZEH
• Pfam ID: PF13499 ; PF08726 ; PF00018 ; PF00435
• Sequence:
  MDPSGVKVLETAEDIQERRQQVLDRYHRFKELSTLRRQKLEDSYRFQFFQRDAEELEKWI
  QEKLQIASDENYKDPTNLQGKLQKHQAFEAEVQANSGAIVKLDETGNLMISEGHFASETI
  RTRLMELHRQWELLLEKMREKGIKLLQAQKLVQYLRECEDVMDWINDKEAIVTSEELGQD
  LEHVEVLQKKFEEFQTDMAAHEERVNEVNQFAAKLIQEQHPEEELIKTKQDEVNAAWQRL
  KGLALQRQGKLFGAAEVQRFNRDVDETISWIKEKEQLMASDDFGRDLASVQALLRKHEGL
  ERDLAALEDKVKALCAEADRLQQSHPLSATQIQVKREELITNWEQIRTLAAERHARLNDS
  YRLQRFLADFRDLTSWVTEMKALINADELASDVAGAEALLDRHQEHKGEIDAHEDSFKSA
  DESGQALLAAGHYASDEVREKLTVLSEERAALLELWELRRQQYEQCMDLQLFYRDTEQVD
  NWMSKQEAFLLNEDLGDSLDSVEALLKKHEDFEKSLSAQEEKITALDEFATKLIQNNHYA
  MEDVATRRDALLSRRNALHERAMRRRAQLADSFHLQQFFRDSDELKSWVNEKMKTATDEA
  YKDPSNLQGKVQKHQAFEAELSANQSRIDALEKAGQKLIDVNHYAKDEVAARMNEVISLW
  KKLLEATELKGIKLREANQQQQFNRNVEDIELWLYEVEGHLASDDYGKDLTNVQNLQKKH
  ALLEADVAAHQDRIDGITIQARQFQDAGHFDAENIKKKQEALVARYEALKEPMVARKQKL
  ADSLRLQQLFRDVEDEETWIREKEPIAASTNRGKDLIGVQNLLKKHQALQAEIAGHEPRI
  KAVTQKGNAMVEEGHFAAEDVKAKLHELNQKWEALKAKASQRRQDLEDSLQAQQYFADAN
  EAESWMREKEPIVGSTDYGKDEDSAEALLKKHEALMSDLSAYGSSIQALREQAQSCRQQV
  APTDDETGKELVLALYDYQEKSPREVTMKKGDILTLLNSTNKDWWKVEVNDRQGFVPAAY
  VKKLDPAQSASRENLLEEQGSIALRQEQIDNQTRITKEAGSVSLRMKQVEELYHSLLELG
  EKRKGMLEKSCKKFMLFREANELQQWINEKEAALTSEEVGADLEQVEVLQKKFDDFQKDL
  KANESRLKDINKVAEDLESEGLMAEEVQAVQQQEVYGMMPRDETDSKTASPWKSARLMVH
  TVATFNSIKELNERWRSLQQLAEERSQLLGSAHEVQRFHRDADETKEWIEEKNQALNTDN
  YGHDLASVQALQRKHEGFERDLAALGDKVNSLGETAERLIQSHPESAEDLQEKCTELNQA
  WSSLGKRADQRKAKLGDSHDLQRFLSDFRDLMSWINGIRGLVSSDELAKDVTGAEALLER
  HQEHRTEIDARAGTFQAFEQFGQQLLAHGHYASPEIKQKLDILDQERADLEKAWVQRRMM
  LDQCLELQLFHRDCEQAENWMAAREAFLNTEDKGDSLDSVEALIKKHEDFDKAINVQEEK
  IAALQAFADQLIAAGHYAKGDISSRRNEVLDRWRRLKAQMIEKRSKLGESQTLQQFSRDV
  DEIEAWISEKLQTASDESYKDPTNIQSKHQKHQAFEAELHANADRIRGVIDMGNSLIERG
  ACAGSEDAVKARLAALADQWQFLVQKSAEKSQKLKEANKQQNFNTGIKDFDFWLSEVEAL
  LASEDYGKDLASVNNLLKKHQLLEADISAHEDRLKDLNSQADSLMTSSAFDTSQVKDKRD
  TINGRFQKIKSMAASRRAKLNESHRLHQFFRDMDDEESWIKEKKLLVGSEDYGRDLTGVQ
  NLRKKHKRLEAELAAHEPAIQGVLDTGKKLSDDNTIGKEEIQQRLAQFVEHWKELKQLAA
  ARGQRLEESLEYQQFVANVEEEEAWINEKMTLVASEDYGDTLAAIQGLLKKHEAFETDFT
  VHKDRVNDVCTNGQDLIKKNNHHEENISSKMKGLNGKVSDLEKAAAQRKAKLDENSAFLQ
  FNWKADVVESWIGEKENSLKTDDYGRDLSSVQTLLTKQETFDAGLQAFQQEGIANITALK
  DQLLAAKHVQSKAIEARHASLMKRWSQLLANSAARKKKLLEAQSHFRKVEDLFLTFAKKA
  SAFNSWFENAEEDLTDPVRCNSLEEIKALREAHDAFRSSLSSAQADFNQLAELDRQIKSF
  RVASNPYTWFTMEALEETWRNLQKIIKERELELQKEQRRQEENDKLRQEFAQHANAFHQW
  IQETRTYLLDGSCMVEESGTLESQLEATKRKHQEIRAMRSQLKKIEDLGAAMEEALILDN
  KYTEHSTVGLAQQWDQLDQLGMRMQHNLEQQIQARNTTGVTEEALKEFSMMFKHFDKDKS
  GRLNHQEFKSCLRSLGYDLPMVEEGEPDPEFEAILDTVDPNRDGHVSLQEYMAFMISRET
  ENVKSSEEIESAFRALSSEGKPYVTKEELYQNLTREQADYCVSHMKPYVDGKGRELPTAF
  DYVEFTRSLFVN
• Function: Fodrin, which seems to be involved in secretion, interacts with calmodulin in a calcium-dependent manner and is thus candidate for the calcium-dependent movement of the cytoskeleton at the membrane.
• KEGG Pathway:
  Apoptosis (hsa04210)
  Cytoskeleton in muscle cells (hsa04820)
• Reactome Pathway:
  Nephrin family interactions (R-HSA-373753)
  NCAM signaling for neurite out-growth (R-HSA-375165)
  Interaction between L1 and Ankyrins (R-HSA-445095)
  RAF/MAP kinase cascade (R-HSA-5673001)
  Neutrophil degranulation (R-HSA-6798695)
  COPI-mediated anterograde transport (R-HSA-6807878)
  RHOU GTPase cycle (R-HSA-9013420)
  RHOV GTPase cycle (R-HSA-9013424)
  Sensory processing of sound by inner hair cells of the cochlea (R-HSA-9662360)
  Sensory processing of sound by outer hair cells of the cochlea (R-HSA-9662361)
  Caspase-mediated cleavage of cytoskeletal proteins (R-HSA-264870)

Molecular Interaction Atlas (MIA) of This DOT

35 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Developmental and epileptic encephalopathy, 5	DIS2R0FL	Definitive	Autosomal dominant	[1]
Epilepsy	DISBB28L	Definitive	Genetic Variation	[2]
Infantile spasm	DISZSKDG	Definitive	Autosomal dominant	[3]
Acute erythroid leukemia	DISZFC1O	Strong	Altered Expression	[4]
Adult T-cell leukemia/lymphoma	DIS882XU	Strong	Biomarker	[5]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[6]
Autoimmune disease	DISORMTM	Strong	Biomarker	[7]
Cardiac failure	DISDC067	Strong	Biomarker	[8]
Childhood epilepsy with centrotemporal spikes	DISKT2L5	Strong	CausalMutation	[9]
Colon cancer	DISVC52G	Strong	Altered Expression	[10]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[10]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[8]
Early myoclonic encephalopathy	DIS1YXVQ	Strong	Genetic Variation	[11]
Fanconi anemia complementation group A	DIS8PZLI	Strong	Biomarker	[12]
Fanconi's anemia	DISGW6Q8	Strong	Biomarker	[12]
Gastric cancer	DISXGOUK	Strong	Biomarker	[13]
Infantile epileptic-dyskinetic encephalopathy	DISD2ZNC	Strong	Genetic Variation	[14]
Migraine disorder	DISFCQTG	Strong	Biomarker	[15]
Migraine with aura	DISDM7I8	Strong	Altered Expression	[15]
Moyamoya disease	DISO62CA	Strong	Biomarker	[16]
Myopathy	DISOWG27	Strong	Altered Expression	[17]
Nervous system disease	DISJ7GGT	Strong	Genetic Variation	[8]
Refractory chronic myeloid leukaemia	DIS40YPP	Strong	Genetic Variation	[18]
Sjogren syndrome	DISUBX7H	Strong	Biomarker	[19]
Stomach cancer	DISKIJSX	Strong	Biomarker	[13]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[7]
T-cell leukaemia	DISJ6YIF	Strong	Biomarker	[5]
Vascular purpura	DIS6ZZMF	Strong	Genetic Variation	[20]
Isolated congenital microcephaly	DISUXHZ6	moderate	Genetic Variation	[21]
West syndrome	DISLIAU9	Supportive	Autosomal dominant	[22]
Subarachnoid hemorrhage	DISI7I8Y	Disputed	Biomarker	[23]
Tuberculosis	DIS2YIMD	Disputed	Altered Expression	[24]
Colorectal carcinoma	DIS5PYL0	Limited	Biomarker	[6]
Intellectual disability	DISMBNXP	Limited	Genetic Variation	[25]
Neoplasm	DISZKGEW	Limited	Altered Expression	[6]

23 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 Spectrin alpha chain, non-erythrocytic 1 (SPTAN1).	[26]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Spectrin alpha chain, non-erythrocytic 1 (SPTAN1).	[27]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Spectrin alpha chain, non-erythrocytic 1 (SPTAN1).	[28]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Spectrin alpha chain, non-erythrocytic 1 (SPTAN1).	[29]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Spectrin alpha chain, non-erythrocytic 1 (SPTAN1).	[30]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Spectrin alpha chain, non-erythrocytic 1 (SPTAN1).	[31]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Spectrin alpha chain, non-erythrocytic 1 (SPTAN1).	[32]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Spectrin alpha chain, non-erythrocytic 1 (SPTAN1).	[33]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Spectrin alpha chain, non-erythrocytic 1 (SPTAN1).	[34]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Spectrin alpha chain, non-erythrocytic 1 (SPTAN1).	[35]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Spectrin alpha chain, non-erythrocytic 1 (SPTAN1).	[36]
Selenium	DM25CGV	Approved	Selenium increases the expression of Spectrin alpha chain, non-erythrocytic 1 (SPTAN1).	[37]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Spectrin alpha chain, non-erythrocytic 1 (SPTAN1).	[38]
Aspirin	DM672AH	Approved	Aspirin decreases the expression of Spectrin alpha chain, non-erythrocytic 1 (SPTAN1).	[40]
Menthol	DMG2KW7	Approved	Menthol decreases the expression of Spectrin alpha chain, non-erythrocytic 1 (SPTAN1).	[41]
Romidepsin	DMT5GNL	Approved	Romidepsin increases the expression of Spectrin alpha chain, non-erythrocytic 1 (SPTAN1).	[42]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Spectrin alpha chain, non-erythrocytic 1 (SPTAN1).	[43]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Spectrin alpha chain, non-erythrocytic 1 (SPTAN1).	[37]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Spectrin alpha chain, non-erythrocytic 1 (SPTAN1).	[45]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Spectrin alpha chain, non-erythrocytic 1 (SPTAN1).	[46]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Spectrin alpha chain, non-erythrocytic 1 (SPTAN1).	[49]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Spectrin alpha chain, non-erythrocytic 1 (SPTAN1).	[50]
GALLICACID	DM6Y3A0	Investigative	GALLICACID decreases the expression of Spectrin alpha chain, non-erythrocytic 1 (SPTAN1).	[51]

4 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the cleavage of Spectrin alpha chain, non-erythrocytic 1 (SPTAN1).	[39]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the cleavage of Spectrin alpha chain, non-erythrocytic 1 (SPTAN1).	[44]
Staurosporine	DM0E9BR	Investigative	Staurosporine increases the cleavage of Spectrin alpha chain, non-erythrocytic 1 (SPTAN1).	[52]
Chelerythrine	DMCP1G9	Investigative	Chelerythrine increases the cleavage of Spectrin alpha chain, non-erythrocytic 1 (SPTAN1).	[52]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of Spectrin alpha chain, non-erythrocytic 1 (SPTAN1).	[47]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Spectrin alpha chain, non-erythrocytic 1 (SPTAN1).	[48]

References

• [1] The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources. Genet Med. 2022 Aug;24(8):1732-1742. doi: 10.1016/j.gim.2022.04.017. Epub 2022 May 4.
• [2] Novel variants in SPTAN1 without epilepsy: An expansion of the phenotype.Am J Med Genet A. 2018 Dec;176(12):2768-2776. doi: 10.1002/ajmg.a.40628. Epub 2018 Dec 11.
• [3] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [4] Patterns of spectrin transcripts in erythroid and non-erythroid cells.J Cell Physiol. 1990 Aug;144(2):287-94. doi: 10.1002/jcp.1041440215.
• [5] Preapoptotic protease calpain-2 is frequently suppressed in adult T-cell leukemia.Blood. 2013 May 23;121(21):4340-7. doi: 10.1182/blood-2012-08-446922. Epub 2013 Mar 28.
• [6] Downregulation of SPTAN1 is related to MLH1 deficiency and metastasis in colorectal cancer.PLoS One. 2019 Mar 11;14(3):e0213411. doi: 10.1371/journal.pone.0213411. eCollection 2019.
• [7] Autoantibodies to alpha-fodrin in primary Sjgren's syndrome and SLE detected by an in vitro transcription and translation assay.Clin Exp Rheumatol. 2003 Jan-Feb;21(1):49-56.
• [8] Defining new mechanistic roles for II spectrin in cardiac function.J Biol Chem. 2019 Jun 14;294(24):9576-9591. doi: 10.1074/jbc.RA119.007714. Epub 2019 May 7.
• [9] Exome-wide analysis of mutational burden in patients with typical and atypical Rolandic epilepsy.Eur J Hum Genet. 2018 Feb;26(2):258-264. doi: 10.1038/s41431-017-0034-x. Epub 2018 Jan 22.
• [10] Reduced migration of MLH1 deficient colon cancer cells depends on SPTAN1.Mol Cancer. 2014 Jan 24;13:11. doi: 10.1186/1476-4598-13-11.
• [11] Early myoclonic encephalopathy in 9q33-q34 deletion encompassing STXBP1 and SPTAN1.Ann Hum Genet. 2015 May;79(3):209-17. doi: 10.1111/ahg.12106. Epub 2015 Mar 16.
• [12] Spectrin and its interacting partners in nuclear structure and function.Exp Biol Med (Maywood). 2018 Mar;243(6):507-524. doi: 10.1177/1535370218763563.
• [13] Identification of genes differentially expressed between gastric cancers and normal gastric mucosa with cDNA microarrays.Cancer Lett. 2002 Oct 28;184(2):197-206. doi: 10.1016/s0304-3835(02)00197-0.
• [14] Novel 9q34.11 gene deletions encompassing combinations of four Mendelian disease genes: STXBP1, SPTAN1, ENG, and TOR1A.Genet Med. 2012 Oct;14(10):868-76. doi: 10.1038/gim.2012.65. Epub 2012 Jun 21.
• [15] Identification of biomarkers associated with migraine with aura.Neurosci Res. 2009 May;64(1):104-10. doi: 10.1016/j.neures.2009.02.001. Epub 2009 Feb 13.
• [16] Anti-alpha-fodrin autoantibodies in Moyamoya disease.Stroke. 2003 Dec;34(12):e244-6. doi: 10.1161/01.STR.0000100479.63243.48. Epub 2003 Dec 1.
• [17] Calpain-dependent alpha-fodrin cleavage at the sarcolemma in muscle diseases.Muscle Nerve. 2005 Sep;32(3):303-9. doi: 10.1002/mus.20362.
• [18] Identification of a novel CSF3R-SPTAN1 fusion gene in an atypical chronic myeloid leukemia patient with t(1;9)(p34;q34) by RNA-Seq.Cancer Genet. 2017 Oct;216-217:16-19. doi: 10.1016/j.cancergen.2017.05.002. Epub 2017 May 24.
• [19] Clinical and immunological characteristics of patients with Sjgren's syndrome in relation to alpha-fodrin antibodies.Rheumatology (Oxford). 2007 Mar;46(3):479-83. doi: 10.1093/rheumatology/kel270. Epub 2006 Aug 25.
• [20] SPTAN1 variants as a potential cause for autosomal recessive hereditary spastic paraplegia.J Hum Genet. 2019 Nov;64(11):1145-1151. doi: 10.1038/s10038-019-0669-2. Epub 2019 Sep 12.
• [21] SPTAN1 encephalopathy: distinct phenotypes and genotypes.J Hum Genet. 2015 Apr;60(4):167-73. doi: 10.1038/jhg.2015.5. Epub 2015 Jan 29.
• [22] Genes of early-onset epileptic encephalopathies: from genotype to phenotype. Pediatr Neurol. 2012 Jan;46(1):24-31. doi: 10.1016/j.pediatrneurol.2011.11.003.
• [23] Evaluation of alpha-II-spectrin breakdown products as potential biomarkers for early recognition and severity of aneurysmal subarachnoid hemorrhage.Sci Rep. 2018 Sep 6;8(1):13308. doi: 10.1038/s41598-018-31631-y.
• [24] Differential expression of alpha II spectrin in monocytes of tuberculosis patients.Int Immunopharmacol. 2013 Nov;17(3):759-62. doi: 10.1016/j.intimp.2013.09.005. Epub 2013 Sep 18.
• [25] Identification of a novel in-frame de novo mutation in SPTAN1 in intellectual disability and pontocerebellar atrophy.Eur J Hum Genet. 2012 Jul;20(7):796-800. doi: 10.1038/ejhg.2011.271. Epub 2012 Jan 18.
• [26] 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.
• [27] 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.
• [28] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [29] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [30] 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.
• [31] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [32] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [33] 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.
• [34] Gene expression profile changes in NB4 cells induced by arsenic trioxide. Acta Pharmacol Sin. 2003 Jul;24(7):646-50.
• [35] Functional gene expression profile underlying methotrexate-induced senescence in human colon cancer cells. Tumour Biol. 2011 Oct;32(5):965-76.
• [36] Zoledronate dysregulates fatty acid metabolism in renal tubular epithelial cells to induce nephrotoxicity. Arch Toxicol. 2018 Jan;92(1):469-485.
• [37] 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.
• [38] New insights into the mechanisms underlying 5-fluorouracil-induced intestinal toxicity based on transcriptomic and metabolomic responses in human intestinal organoids. Arch Toxicol. 2021 Aug;95(8):2691-2718. doi: 10.1007/s00204-021-03092-2. Epub 2021 Jun 20.
• [39] Dexamethasone induces apoptosis in proliferative chondrocytes through activation of caspases and suppression of the Akt-phosphatidylinositol 3'-kinase signaling pathway. Endocrinology. 2005 Mar;146(3):1391-7. doi: 10.1210/en.2004-1152. Epub 2004 Dec 2.
• [40] Effects of aspirin on metastasis-associated gene expression detected by cDNA microarray. Acta Pharmacol Sin. 2004 Oct;25(10):1327-33.
• [41] Repurposing L-menthol for systems medicine and cancer therapeutics? L-menthol induces apoptosis through caspase 10 and by suppressing HSP90. OMICS. 2016 Jan;20(1):53-64.
• [42] 5-Aza-2'-deoxycytidine and depsipeptide synergistically induce expression of BIK (BCL2-interacting killer). Biochem Biophys Res Commun. 2006 Dec 15;351(2):455-61. doi: 10.1016/j.bbrc.2006.10.055. Epub 2006 Oct 18.
• [43] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [44] Calpain and caspase orchestrated death signal to accomplish apoptosis induced by resveratrol and its novel analog hydroxystilbene-1 [correction of hydroxstilbene-1] in cancer cells. J Pharmacol Exp Ther. 2010 Aug;334(2):381-94. doi: 10.1124/jpet.110.167668. Epub 2010 May 18.
• [45] Label-free quantitative proteomic analysis identifies the oncogenic role of FOXA1 in BaP-transformed 16HBE cells. Toxicol Appl Pharmacol. 2020 Sep 15;403:115160. doi: 10.1016/j.taap.2020.115160. Epub 2020 Jul 25.
• [46] Targeting MYCN in neuroblastoma by BET bromodomain inhibition. Cancer Discov. 2013 Mar;3(3):308-23.
• [47] 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.
• [48] 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.
• [49] Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model. Environ Pollut. 2023 Oct 15;335:122359. doi: 10.1016/j.envpol.2023.122359. Epub 2023 Aug 9.
• [50] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [51] Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743. doi: 10.1038/s41598-021-96174-1.
• [52] An Early and Robust Activation of Caspases Heads Cells for a Regulated Form of Necrotic-like Cell Death. J Biol Chem. 2015 Aug 21;290(34):20841-20855. doi: 10.1074/jbc.M115.644179. Epub 2015 Jun 29.