Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6XJCZH)

• DOT Name: Microphthalmia-associated transcription factor (MITF)
• Synonyms: Class E basic helix-loop-helix protein 32; bHLHe32
• Gene Name: MITF
• Related Disease:
  Obsolete ocular albinism with congenital sensorineural hearing loss
  Tietz syndrome
  Waardenburg syndrome type 2
  Waardenburg syndrome type 2A
  Advanced cancer
  Albinism
  Attention deficit hyperactivity disorder
  B-cell neoplasm
  Camurati-Engelmann disease
  Clear cell renal carcinoma
  Clear cell sarcoma
  Coloboma, osteopetrosis, microphthalmia, macrocephaly, albinism, and deafness
  Constipation
  Cutaneous melanoma
  Familial atypical multiple mole melanoma syndrome
  Hepatocellular carcinoma
  Kidney cancer
  Kidney neoplasm
  Melanocytic nevus
  Melanoma, cutaneous malignant, susceptibility to, 8
  Neoplasm
  Neoplasm with perivascular epithelioid cell differentiation
  Ocular albinism
  Papillary renal cell carcinoma
  Renal carcinoma
  Sensorineural hearing loss disorder
  Vitiligo
  Waardenburg syndrome type 4A
  Hirschsprung disease
  Hypopigmentation of the skin
  Renal cell carcinoma
  Waardenburg-Shah syndrome
  Hereditary neoplastic syndrome
  Metastatic melanoma
  Breast neoplasm
  Gastric cancer
  Hereditary pheochromocytoma-paraganglioma
  Microphthalmia
  Oculocutaneous albinism
  Sarcoma
  Stomach cancer
  Waardenburg syndrome type 2E
• UniProt ID: MITF_HUMAN
• PDB ID: 4C7N; 7D8R; 7D8S; 7D8T; 7EOD; 8E1D
• Pfam ID: PF11851 ; PF00010 ; PF15951
• Sequence:
  MQSESGIVPDFEVGEEFHEEPKTYYELKSQPLKSSSSAEHPGASKPPISSSSMTSRILLR
  QQLMREQMQEQERREQQQKLQAAQFMQQRVPVSQTPAINVSVPTTLPSATQVPMEVLKVQ
  THLENPTKYHIQQAQRQQVKQYLSTTLANKHANQVLSLPCPNQPGDHVMPPVPGSSAPNS
  PMAMLTLNSNCEKEGFYKFEEQNRAESECPGMNTHSRASCMQMDDVIDDIISLESSYNEE
  ILGLMDPALQMANTLPVSGNLIDLYGNQGLPPPGLTISNSCPANLPNIKRELTACIFPTE
  SEARALAKERQKKDNHNLIERRRRFNINDRIKELGTLIPKSNDPDMRWNKGTILKASVDY
  IRKLQREQQRAKELENRQKKLEHANRHLLLRIQELEMQARAHGLSLIPSTGLCSPDLVNR
  IIKQEPVLENCSQDLLQHHADLTCTTTLDLTDGTITFNNNLGTGTEANQAYSVPTKMGSK
  LEDILMDDTLSPVGVTDPLLSSVSPGASKTSSRRSSMSMEETEHTC
• Function: Transcription factor that acts as a master regulator of melanocyte survival and differentiation as well as melanosome biogenesis. Binds to M-boxes (5'-TCATGTG-3') and symmetrical DNA sequences (E-boxes) (5'-CACGTG-3') found in the promoter of pigmentation genes, such as tyrosinase (TYR). Involved in the cellular response to amino acid availability by acting downstream of MTOR: in the presence of nutrients, MITF phosphorylation by MTOR promotes its inactivation. Upon starvation or lysosomal stress, inhibition of MTOR induces MITF dephosphorylation, resulting in transcription factor activity. Plays an important role in melanocyte development by regulating the expression of tyrosinase (TYR) and tyrosinase-related protein 1 (TYRP1). Plays a critical role in the differentiation of various cell types, such as neural crest-derived melanocytes, mast cells, osteoclasts and optic cup-derived retinal pigment epithelium.
• Tissue Specificity: Expressed in melanocytes (at protein level).; [Isoform A2]: Expressed in the retinal pigment epithelium, brain, and placenta . Expressed in the kidney .; [Isoform C2]: Expressed in the kidney and retinal pigment epithelium.; [Isoform H1]: Expressed in the kidney.; [Isoform H2]: Expressed in the kidney.; [Isoform M1]: Expressed in melanocytes.; [Isoform Mdel]: Expressed in melanocytes.
• KEGG Pathway:
  Mitophagy - animal (hsa04137)
  Osteoclast differentiation (hsa04380)
  Melanogenesis (hsa04916)
  Pathways in cancer (hsa05200)
  Transcriptio.l misregulation in cancer (hsa05202)
  Melanoma (hsa05218)
• Reactome Pathway: SUMOylation of transcription factors (R-HSA-3232118)

Molecular Interaction Atlas (MIA) of This DOT

42 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Obsolete ocular albinism with congenital sensorineural hearing loss	DIS0CTBN	Definitive	Autosomal dominant	[1]
Tietz syndrome	DISDORP9	Definitive	Autosomal dominant	[2]
Waardenburg syndrome type 2	DISVZBEV	Definitive	Autosomal dominant	[3]
Waardenburg syndrome type 2A	DISM4IVI	Definitive	Autosomal dominant	[4]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[5]
Albinism	DIS5D82I	Strong	Genetic Variation	[6]
Attention deficit hyperactivity disorder	DISL8MX9	Strong	CausalMutation	[7]
B-cell neoplasm	DISVY326	Strong	Genetic Variation	[8]
Camurati-Engelmann disease	DISTJPCE	Strong	Biomarker	[9]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[10]
Clear cell sarcoma	DIS1MTE6	Strong	Biomarker	[11]
Coloboma, osteopetrosis, microphthalmia, macrocephaly, albinism, and deafness	DIS3J7QL	Strong	Autosomal recessive	[12]
Constipation	DISRQXWI	Strong	CausalMutation	[7]
Cutaneous melanoma	DIS3MMH9	Strong	Biomarker	[13]
Familial atypical multiple mole melanoma syndrome	DIS2YEKP	Strong	SusceptibilityMutation	[14]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[15]
Kidney cancer	DISBIPKM	Strong	Genetic Variation	[16]
Kidney neoplasm	DISBNZTN	Strong	Genetic Variation	[17]
Melanocytic nevus	DISYS32D	Strong	Genetic Variation	[18]
Melanoma, cutaneous malignant, susceptibility to, 8	DISL8RLW	Strong	Autosomal dominant	[19]
Neoplasm	DISZKGEW	Strong	Altered Expression	[11]
Neoplasm with perivascular epithelioid cell differentiation	DIS8V0NT	Strong	Biomarker	[20]
Ocular albinism	DIS5IHK1	Strong	Biomarker	[21]
Papillary renal cell carcinoma	DIS25HBV	Strong	Biomarker	[19]
Renal carcinoma	DISER9XT	Strong	Genetic Variation	[16]
Sensorineural hearing loss disorder	DISJV45Z	Strong	Genetic Variation	[22]
Vitiligo	DISR05SL	Strong	Altered Expression	[23]
Waardenburg syndrome type 4A	DISSMGSQ	Strong	GermlineCausalMutation	[24]
Hirschsprung disease	DISUUSM1	moderate	Genetic Variation	[25]
Hypopigmentation of the skin	DIS39YKC	moderate	Genetic Variation	[26]
Renal cell carcinoma	DISQZ2X8	Moderate	Autosomal dominant	[27]
Waardenburg-Shah syndrome	DISR8C6R	Supportive	Autosomal dominant	[24]
Hereditary neoplastic syndrome	DISGXLG5	Disputed	CausalMutation	[28]
Metastatic melanoma	DISSL43L	Disputed	Altered Expression	[29]
Breast neoplasm	DISNGJLM	Limited	Biomarker	[30]
Gastric cancer	DISXGOUK	Limited	Altered Expression	[31]
Hereditary pheochromocytoma-paraganglioma	DISP9K7L	Limited	Biomarker	[32]
Microphthalmia	DISGEBES	Limited	Genetic Variation	[6]
Oculocutaneous albinism	DISJS7CU	Limited	Genetic Variation	[33]
Sarcoma	DISZDG3U	Limited	Biomarker	[11]
Stomach cancer	DISKIJSX	Limited	Altered Expression	[31]
Waardenburg syndrome type 2E	DISDMDVH	Limited	Biomarker	[4]

35 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 Microphthalmia-associated transcription factor (MITF).	[34]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Microphthalmia-associated transcription factor (MITF).	[35]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Microphthalmia-associated transcription factor (MITF).	[36]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Microphthalmia-associated transcription factor (MITF).	[37]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Microphthalmia-associated transcription factor (MITF).	[38]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Microphthalmia-associated transcription factor (MITF).	[39]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Microphthalmia-associated transcription factor (MITF).	[40]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Microphthalmia-associated transcription factor (MITF).	[41]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Microphthalmia-associated transcription factor (MITF).	[42]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Microphthalmia-associated transcription factor (MITF).	[43]
Decitabine	DMQL8XJ	Approved	Decitabine decreases the expression of Microphthalmia-associated transcription factor (MITF).	[44]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Microphthalmia-associated transcription factor (MITF).	[45]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Microphthalmia-associated transcription factor (MITF).	[46]
Melphalan	DMOLNHF	Approved	Melphalan decreases the expression of Microphthalmia-associated transcription factor (MITF).	[47]
Alitretinoin	DMME8LH	Approved	Alitretinoin increases the expression of Microphthalmia-associated transcription factor (MITF).	[48]
Ciprofloxacin XR	DM2NLS9	Approved	Ciprofloxacin XR decreases the expression of Microphthalmia-associated transcription factor (MITF).	[49]
Vemurafenib	DM62UG5	Approved	Vemurafenib affects the expression of Microphthalmia-associated transcription factor (MITF).	[50]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Microphthalmia-associated transcription factor (MITF).	[51]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Microphthalmia-associated transcription factor (MITF).	[52]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Microphthalmia-associated transcription factor (MITF).	[53]
Chlorpromazine	DMBGZI3	Phase 3 Trial	Chlorpromazine increases the expression of Microphthalmia-associated transcription factor (MITF).	[54]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Microphthalmia-associated transcription factor (MITF).	[55]
PMID26394986-Compound-22	DM43Z1G	Patented	PMID26394986-Compound-22 increases the expression of Microphthalmia-associated transcription factor (MITF).	[58]
Torcetrapib	DMDHYM7	Discontinued in Phase 2	Torcetrapib increases the expression of Microphthalmia-associated transcription factor (MITF).	[59]
MG-132	DMKA2YS	Preclinical	MG-132 decreases the expression of Microphthalmia-associated transcription factor (MITF).	[60]
EMODIN	DMAEDQG	Terminated	EMODIN decreases the expression of Microphthalmia-associated transcription factor (MITF).	[61]
Calphostin C	DM9X2D0	Terminated	Calphostin C affects the expression of Microphthalmia-associated transcription factor (MITF).	[62]
Pifithrin-alpha	DM63OD7	Terminated	Pifithrin-alpha decreases the expression of Microphthalmia-associated transcription factor (MITF).	[63]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Microphthalmia-associated transcription factor (MITF).	[65]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Microphthalmia-associated transcription factor (MITF).	[66]
Paraquat	DMR8O3X	Investigative	Paraquat increases the expression of Microphthalmia-associated transcription factor (MITF).	[58]
4-hydroxy-2-nonenal	DM2LJFZ	Investigative	4-hydroxy-2-nonenal decreases the expression of Microphthalmia-associated transcription factor (MITF).	[48]
Lithium chloride	DMHYLQ2	Investigative	Lithium chloride increases the expression of Microphthalmia-associated transcription factor (MITF).	[68]
Forskolin	DM6ITNG	Investigative	Forskolin increases the expression of Microphthalmia-associated transcription factor (MITF).	[69]
CyPPA	DM64L9I	Investigative	CyPPA decreases the expression of Microphthalmia-associated transcription factor (MITF).	[70]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Microphthalmia-associated transcription factor (MITF).	[56]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of Microphthalmia-associated transcription factor (MITF).	[57]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the methylation of Microphthalmia-associated transcription factor (MITF).	[64]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of Microphthalmia-associated transcription factor (MITF).	[67]

References

• [1] Flexible and scalable diagnostic filtering of genomic variants using G2P with Ensembl VEP. Nat Commun. 2019 May 30;10(1):2373. doi: 10.1038/s41467-019-10016-3.
• [2] The mutational spectrum in Waardenburg syndrome. Hum Mol Genet. 1995 Nov;4(11):2131-7. doi: 10.1093/hmg/4.11.2131.
• [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] Apparent digenic inheritance of Waardenburg syndrome type 2 (WS2) and autosomal recessive ocular albinism (AROA). Hum Mol Genet. 1997 May;6(5):659-64. doi: 10.1093/hmg/6.5.659.
• [5] Microphthalmia-Associated Transcription Factor (MITF) Regulates Immune Cell Migration into Melanoma.Transl Oncol. 2019 Feb;12(2):350-360. doi: 10.1016/j.tranon.2018.10.014. Epub 2018 Nov 28.
• [6] The transcription factor MITF in RPE function and dysfunction.Prog Retin Eye Res. 2019 Nov;73:100766. doi: 10.1016/j.preteyeres.2019.06.002. Epub 2019 Jun 23.
• [7] Prevalence of MITF p.E318K in Patients With Melanoma Independent of the Presence of CDKN2A Causative Mutations.JAMA Dermatol. 2016 Apr;152(4):405-12. doi: 10.1001/jamadermatol.2015.4356.
• [8] Potential Prognostic Molecular Signatures in a Preclinical Model of Melanoma.Anticancer Res. 2017 Jan;37(1):143-148. doi: 10.21873/anticanres.11299.
• [9] Mitf and Tfe3, two members of the Mitf-Tfe family of bHLH-Zip transcription factors, have important but functionally redundant roles in osteoclast development.Proc Natl Acad Sci U S A. 2002 Apr 2;99(7):4477-82. doi: 10.1073/pnas.072071099.
• [10] Progress of small ubiquitin-related modifiers in kidney diseases.Chin Med J (Engl). 2019 Feb;132(4):466-473. doi: 10.1097/CM9.0000000000000094.
• [11] Eribulin Suppresses Clear Cell Sarcoma Growth by Inhibiting Cell Proliferation and Inducing Melanocytic Differentiation Both Directly and Via Vascular Remodeling.Mol Cancer Ther. 2020 Mar;19(3):742-754. doi: 10.1158/1535-7163.MCT-19-0358. Epub 2019 Dec 3.
• [12] Biallelic Mutations in MITF Cause Coloboma, Osteopetrosis, Microphthalmia, Macrocephaly, Albinism, and Deafness. Am J Hum Genet. 2016 Dec 1;99(6):1388-1394. doi: 10.1016/j.ajhg.2016.11.004. Epub 2016 Nov 23.
• [13] PAX3d mRNA over 2.76 copies/L in the bloodstream predicts cutaneous malignant melanoma relapse.Oncotarget. 2017 Aug 11;8(49):85479-85491. doi: 10.18632/oncotarget.20177. eCollection 2017 Oct 17.
• [14] Genetics of familial melanoma: 20 years after CDKN2A.Pigment Cell Melanoma Res. 2015 Mar;28(2):148-60. doi: 10.1111/pcmr.12333. Epub 2015 Jan 5.
• [15] Multi-color RGB marking enables clonality assessment of liver tumors in a murine xenograft model.Oncotarget. 2017 Dec 14;8(70):115582-115595. doi: 10.18632/oncotarget.23312. eCollection 2017 Dec 29.
• [16] Exploring the hereditary background of renal cancer in Denmark.PLoS One. 2019 Apr 29;14(4):e0215725. doi: 10.1371/journal.pone.0215725. eCollection 2019.
• [17] Detection of 6 TFEB-amplified renal cell carcinomas and 25 renal cell carcinomas with MITF translocations: systematic morphologic analysis of 85 cases evaluated by clinical TFE3 and TFEB FISH assays.Mod Pathol. 2018 Jan;31(1):179-197. doi: 10.1038/modpathol.2017.99. Epub 2017 Aug 25.
• [18] Deciphering the Role of Oncogenic MITFE318K in Senescence Delay and Melanoma Progression.J Natl Cancer Inst. 2017 Aug 1;109(8). doi: 10.1093/jnci/djw340.
• [19] A SUMOylation-defective MITF germline mutation predisposes to melanoma and renal carcinoma. Nature. 2011 Oct 19;480(7375):94-8. doi: 10.1038/nature10539.
• [20] Cathepsin K expression in clear cell "sugar" tumor (PEComa) of the lung.Virchows Arch. 2018 Jul;473(1):55-59. doi: 10.1007/s00428-018-2325-1. Epub 2018 Mar 7.
• [21] Clinical and molecular findings of FRMD7 related congenital nystagmus as adifferential diagnosis of ocular albinism.Ophthalmic Genet. 2019 Apr;40(2):161-164. doi: 10.1080/13816810.2019.1592201. Epub 2019 Apr 3.
• [22] Comprehensive genomic diagnosis of non-syndromic and syndromic hereditary hearing loss in Spanish patients.BMC Med Genomics. 2018 Jul 9;11(1):58. doi: 10.1186/s12920-018-0375-5.
• [23] Increased systemic and epidermal levels of IL-17A and IL-1 promotes progression of non-segmental vitiligo.Cytokine. 2017 Mar;91:153-161. doi: 10.1016/j.cyto.2016.12.014. Epub 2017 Jan 9.
• [24] De Novo Variants in MAPK8IP3 Cause Intellectual Disability with Variable Brain Anomalies. Am J Hum Genet. 2019 Feb 7;104(2):203-212. doi: 10.1016/j.ajhg.2018.12.008. Epub 2019 Jan 3.
• [25] Screening of MITF and SOX10 regulatory regions in Waardenburg syndrome type 2.PLoS One. 2012;7(7):e41927. doi: 10.1371/journal.pone.0041927. Epub 2012 Jul 27.
• [26] Whole-genome sequencing reveals a large deletion in the MITF gene in horses with white spotted coat colour and increased risk of deafness.Anim Genet. 2019 Apr;50(2):172-174. doi: 10.1111/age.12762. Epub 2019 Jan 15.
• [27] 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.
• [28] The Microphthalmia-Associated Transcription Factor p.E318K Mutation Does Not Play a Major Role in Sporadic Renal Cell Tumors from Caucasian Patients.Pathobiology. 2016;83(4):165-9. doi: 10.1159/000443311. Epub 2016 Mar 22.
• [29] The X-Linked DDX3X RNA Helicase Dictates Translation Reprogramming and Metastasis in Melanoma.Cell Rep. 2019 Jun 18;27(12):3573-3586.e7. doi: 10.1016/j.celrep.2019.05.069.
• [30] Chromatin-informed inference of transcriptional programs in gynecologic and basal breast cancers.Nat Commun. 2019 Sep 25;10(1):4369. doi: 10.1038/s41467-019-12291-6.
• [31] CSE1L silence inhibits the growth and metastasis in gastric cancer by repressing GPNMB via positively regulating transcription factor MITF.J Cell Physiol. 2020 Mar;235(3):2071-2079. doi: 10.1002/jcp.29107. Epub 2019 Jul 25.
• [32] The MITF, p.E318K Variant, as a Risk Factor for Pheochromocytoma and Paraganglioma.J Clin Endocrinol Metab. 2016 Dec;101(12):4764-4768. doi: 10.1210/jc.2016-2103. Epub 2016 Sep 28.
• [33] Genetic profiling of a rare condition: co-occurrence of albinism and multiple primary melanoma in a Caucasian family.Oncotarget. 2017 May 2;8(18):29751-29759. doi: 10.18632/oncotarget.12777.
• [34] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [35] 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.
• [36] 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.
• [37] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [38] Long-term estrogen exposure promotes carcinogen bioactivation, induces persistent changes in gene expression, and enhances the tumorigenicity of MCF-7 human breast cancer cells. Toxicol Appl Pharmacol. 2009 Nov 1;240(3):355-66.
• [39] 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.
• [40] Integrated assessment by multiple gene expression analysis of quercetin bioactivity on anticancer-related mechanisms in colon cancer cells in vitro. Eur J Nutr. 2005 Mar;44(3):143-56. doi: 10.1007/s00394-004-0503-1. Epub 2004 Apr 30.
• [41] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [42] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [43] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [44] Decitabine up-regulates S100A2 expression and synergizes with IFN-gamma to kill uveal melanoma cells. Clin Cancer Res. 2007 Sep 1;13(17):5219-25. doi: 10.1158/1078-0432.CCR-07-0816.
• [45] Unique transcriptome, pathways, and networks in the human endometrial fibroblast response to progesterone in endometriosis. Biol Reprod. 2011 Apr;84(4):801-15.
• [46] Cannabidiol upregulates melanogenesis through CB1 dependent pathway by activating p38 MAPK and p42/44 MAPK. Chem Biol Interact. 2017 Aug 1;273:107-114. doi: 10.1016/j.cbi.2017.06.005. Epub 2017 Jun 7.
• [47] Bone marrow osteoblast damage by chemotherapeutic agents. PLoS One. 2012;7(2):e30758. doi: 10.1371/journal.pone.0030758. Epub 2012 Feb 17.
• [48] 9-cis retinoic acid is the ALDH1A1 product that stimulates melanogenesis. Exp Dermatol. 2013 Mar;22(3):202-9. doi: 10.1111/exd.12099.
• [49] The role of MITF and Mcl-1 proteins in the antiproliferative and proapoptotic effect of ciprofloxacin in amelanotic melanoma cells: In silico and in vitro study. Toxicol In Vitro. 2020 Aug;66:104884. doi: 10.1016/j.tiv.2020.104884. Epub 2020 May 8.
• [50] PLX4032 Mediated Melanoma Associated Antigen Potentiation in Patient Derived Primary Melanoma Cells. J Cancer. 2015 Oct 29;6(12):1320-30. doi: 10.7150/jca.11126. eCollection 2015.
• [51] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [52] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [53] A novel long noncoding RNA AK001796 acts as an oncogene and is involved in cell growth inhibition by resveratrol in lung cancer. Toxicol Appl Pharmacol. 2015 Jun 1;285(2):79-88.
• [54] Melanogenesis and antioxidant defense system in normal human melanocytes cultured in the presence of chlorpromazine. Toxicol In Vitro. 2015 Feb;29(1):221-7.
• [55] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [56] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [57] 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.
• [58] Celecoxib promotes survival and upregulates the expression of neuroprotective marker genes in two different in vitro models of Parkinson's disease. Neuropharmacology. 2021 Aug 15;194:108378. doi: 10.1016/j.neuropharm.2020.108378. Epub 2020 Nov 6.
• [59] Clarifying off-target effects for torcetrapib using network pharmacology and reverse docking approach. BMC Syst Biol. 2012 Dec 10;6:152.
• [60] Proteasome inhibition creates a chromatin landscape favorable to RNA Pol II processivity. J Biol Chem. 2020 Jan 31;295(5):1271-1287. doi: 10.1074/jbc.RA119.011174. Epub 2019 Dec 5.
• [61] Emodin isolated from Polygoni Multiflori Ramulus inhibits melanogenesis through the liver X receptor-mediated pathway. Chem Biol Interact. 2016 Apr 25;250:78-84. doi: 10.1016/j.cbi.2016.03.014. Epub 2016 Mar 10.
• [62] Targeting the beta-catenin/TCF transcriptional complex in the treatment of multiple myeloma. Proc Natl Acad Sci U S A. 2007 May 1;104(18):7516-21. doi: 10.1073/pnas.0610299104. Epub 2007 Apr 23.
• [63] The essential role of p53 in hyperpigmentation of the skin via regulation of paracrine melanogenic cytokine receptor signaling. J Biol Chem. 2009 Feb 13;284(7):4343-53. doi: 10.1074/jbc.M805570200. Epub 2008 Dec 18.
• [64] 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.
• [65] 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.
• [66] Cystathionine metabolic enzymes play a role in the inflammation resolution of human keratinocytes in response to sub-cytotoxic formaldehyde exposure. Toxicol Appl Pharmacol. 2016 Nov 1;310:185-194.
• [67] 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.
• [68] Effects of lithium and valproic acid on gene expression and phenotypic markers in an NT2 neurosphere model of neural development. PLoS One. 2013;8(3):e58822.
• [69] Post-transcriptional regulation of melanin biosynthetic enzymes by cAMP and resveratrol in human melanocytes. J Invest Dermatol. 2007 Sep;127(9):2216-27. doi: 10.1038/sj.jid.5700840. Epub 2007 Apr 26.
• [70] The ion channel activator CyPPA inhibits melanogenesis via the GSK3/-catenin pathway. Chem Biol Interact. 2019 Feb 25;300:1-7. doi: 10.1016/j.cbi.2018.12.014. Epub 2018 Dec 28.