Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTIIZR61)

• DOT Name: Insulin-like growth factor I (IGF1)
• Synonyms: IGF-I; Mechano growth factor; MGF; Somatomedin-C
• Gene Name: IGF1
• Related Disease: Growth delay due to insulin-like growth factor type 1 deficiency
• UniProt ID: IGF1_HUMAN
• PDB ID: 1B9G; 1BQT; 1GZR; 1GZY; 1GZZ; 1H02; 1H59; 1IMX; 1PMX; 1TGR; 1WQJ; 2DSP; 2DSQ; 2DSR; 2GF1; 3GF1; 3LRI; 4XSS; 5U8Q; 6FF3; 6PYH; 6RVA; 7S0Q; 7WRQ; 7YRR; 8EYR
• Pfam ID: PF00049
• Sequence:
  MGKISSLPTQLFKCCFCDFLKVKMHTMSSSHLFYLALCLLTFTSSATAGPETLCGAELVD
  ALQFVCGDRGFYFNKPTGYGSSSRRAPQTGIVDECCFRSCDLRRLEMYCAPLKPAKSARS
  VRAQRHTDMPKTQKYQPPSTNKNTKSQRRKGWPKTHPGGEQKEGTEASLQIRGKKKEQRR
  EIGSRNAECRGKKGK
• Function: The insulin-like growth factors, isolated from plasma, are structurally and functionally related to insulin but have a much higher growth-promoting activity. May be a physiological regulator of [1-14C]-2-deoxy-D-glucose (2DG) transport and glycogen synthesis in osteoblasts. Stimulates glucose transport in bone-derived osteoblastic (PyMS) cells and is effective at much lower concentrations than insulin, not only regarding glycogen and DNA synthesis but also with regard to enhancing glucose uptake. May play a role in synapse maturation. Ca(2+)-dependent exocytosis of IGF1 is required for sensory perception of smell in the olfactory bulb. Acts as a ligand for IGF1R. Binds to the alpha subunit of IGF1R, leading to the activation of the intrinsic tyrosine kinase activity which autophosphorylates tyrosine residues in the beta subunit thus initiating a cascade of down-stream signaling events leading to activation of the PI3K-AKT/PKB and the Ras-MAPK pathways. Binds to integrins ITGAV:ITGB3 and ITGA6:ITGB4. Its binding to integrins and subsequent ternary complex formation with integrins and IGFR1 are essential for IGF1 signaling. Induces the phosphorylation and activation of IGFR1, MAPK3/ERK1, MAPK1/ERK2 and AKT1. As part of the MAPK/ERK signaling pathway, acts as a negative regulator of apoptosis in cardiomyocytes via promotion of STUB1/CHIP-mediated ubiquitination and degradation of ICER-type isoforms of CREM.
• KEGG Pathway:
  EGFR tyrosine ki.se inhibitor resistance (hsa01521)
  Endocrine resistance (hsa01522)
  MAPK sig.ling pathway (hsa04010)
  Ras sig.ling pathway (hsa04014)
  Rap1 sig.ling pathway (hsa04015)
  HIF-1 sig.ling pathway (hsa04066)
  FoxO sig.ling pathway (hsa04068)
  Oocyte meiosis (hsa04114)
  p53 sig.ling pathway (hsa04115)
  mTOR sig.ling pathway (hsa04150)
  PI3K-Akt sig.ling pathway (hsa04151)
  AMPK sig.ling pathway (hsa04152)
  Longevity regulating pathway (hsa04211)
  Longevity regulating pathway - multiple species (hsa04213)
  Focal adhesion (hsa04510)
  Sig.ling pathways regulating pluripotency of stem cells (hsa04550)
  Long-term depression (hsa04730)
  Inflammatory mediator regulation of TRP channels (hsa04750)
  Ovarian steroidogenesis (hsa04913)
  Progesterone-mediated oocyte maturation (hsa04914)
  Growth hormone synthesis, secretion and action (hsa04935)
  Aldosterone-regulated sodium reabsorption (hsa04960)
  Pathways in cancer (hsa05200)
  Transcriptio.l misregulation in cancer (hsa05202)
  Proteoglycans in cancer (hsa05205)
  Glioma (hsa05214)
  Prostate cancer (hsa05215)
  Melanoma (hsa05218)
  Breast cancer (hsa05224)
  Hypertrophic cardiomyopathy (hsa05410)
  Dilated cardiomyopathy (hsa05414)
• Reactome Pathway:
  Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R) (R-HSA-2404192)
  IRS-related events triggered by IGF1R (R-HSA-2428928)
  SHC-related events triggered by IGF1R (R-HSA-2428933)
  Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) (R-HSA-381426)
  Synthesis, secretion, and deacylation of Ghrelin (R-HSA-422085)
  Platelet degranulation (R-HSA-114608)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Growth delay due to insulin-like growth factor type 1 deficiency	DISHA2HH	Definitive	Autosomal recessive	[1]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Chlorothiazide	DMLHESP	Approved	Insulin-like growth factor I (IGF1) increases the Metabolic disorder ADR of Chlorothiazide.	[56]
Teduglutide	DMYOAKS	Approved	Insulin-like growth factor I (IGF1) increases the Sarcoma ADR of Teduglutide.	[57]

This DOT Affected the Regulation of Drug Effects of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
D-glucose	DMMG2TO	Investigative	Insulin-like growth factor I (IGF1) increases the uptake of D-glucose.	[58]
Deoxythymidine	DMR90HY	Investigative	Insulin-like growth factor I (IGF1) decreases the uptake of Deoxythymidine.	[59]

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 Insulin-like growth factor I (IGF1).	[2]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Insulin-like growth factor I (IGF1).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Insulin-like growth factor I (IGF1).	[45]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Insulin-like growth factor I (IGF1).	[49]

57 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 Insulin-like growth factor I (IGF1).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Insulin-like growth factor I (IGF1).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Insulin-like growth factor I (IGF1).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Insulin-like growth factor I (IGF1).	[6]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Insulin-like growth factor I (IGF1).	[7]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Insulin-like growth factor I (IGF1).	[9]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Insulin-like growth factor I (IGF1).	[10]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Insulin-like growth factor I (IGF1).	[11]
Calcitriol	DM8ZVJ7	Approved	Calcitriol affects the expression of Insulin-like growth factor I (IGF1).	[12]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Insulin-like growth factor I (IGF1).	[13]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Insulin-like growth factor I (IGF1).	[14]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Insulin-like growth factor I (IGF1).	[15]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Insulin-like growth factor I (IGF1).	[16]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Insulin-like growth factor I (IGF1).	[17]
Isotretinoin	DM4QTBN	Approved	Isotretinoin increases the expression of Insulin-like growth factor I (IGF1).	[4]
Ethanol	DMDRQZU	Approved	Ethanol decreases the expression of Insulin-like growth factor I (IGF1).	[19]
Irinotecan	DMP6SC2	Approved	Irinotecan increases the expression of Insulin-like growth factor I (IGF1).	[20]
Clozapine	DMFC71L	Approved	Clozapine decreases the expression of Insulin-like growth factor I (IGF1).	[21]
DTI-015	DMXZRW0	Approved	DTI-015 decreases the expression of Insulin-like growth factor I (IGF1).	[22]
Menthol	DMG2KW7	Approved	Menthol decreases the expression of Insulin-like growth factor I (IGF1).	[23]
Ethinyl estradiol	DMODJ40	Approved	Ethinyl estradiol decreases the expression of Insulin-like growth factor I (IGF1).	[24]
Capsaicin	DMGMF6V	Approved	Capsaicin increases the expression of Insulin-like growth factor I (IGF1).	[25]
Alitretinoin	DMME8LH	Approved	Alitretinoin increases the expression of Insulin-like growth factor I (IGF1).	[4]
Pioglitazone	DMKJ485	Approved	Pioglitazone decreases the expression of Insulin-like growth factor I (IGF1).	[26]
Thalidomide	DM70BU5	Approved	Thalidomide affects the expression of Insulin-like growth factor I (IGF1).	[27]
Bicalutamide	DMZMSPF	Approved	Bicalutamide increases the expression of Insulin-like growth factor I (IGF1).	[13]
Enzalutamide	DMGL19D	Approved	Enzalutamide decreases the expression of Insulin-like growth factor I (IGF1).	[29]
Hydrocortisone	DMGEMB7	Approved	Hydrocortisone decreases the expression of Insulin-like growth factor I (IGF1).	[30]
Bosentan	DMIOGBU	Approved	Bosentan affects the expression of Insulin-like growth factor I (IGF1).	[31]
Bezafibrate	DMZDCS0	Approved	Bezafibrate decreases the expression of Insulin-like growth factor I (IGF1).	[32]
Propofol	DMB4OLE	Approved	Propofol increases the expression of Insulin-like growth factor I (IGF1).	[33]
Sevoflurane	DMC9O43	Approved	Sevoflurane increases the expression of Insulin-like growth factor I (IGF1).	[33]
Adenosine	DMM2NSK	Approved	Adenosine affects the expression of Insulin-like growth factor I (IGF1).	[34]
Methimazole	DM25FL8	Approved	Methimazole decreases the expression of Insulin-like growth factor I (IGF1).	[35]
Estriol	DMOEM2I	Approved	Estriol increases the expression of Insulin-like growth factor I (IGF1).	[36]
Cetrorelix	DMFD9Q6	Approved	Cetrorelix decreases the expression of Insulin-like growth factor I (IGF1).	[38]
Octreotide	DMHIDCJ	Approved	Octreotide decreases the expression of Insulin-like growth factor I (IGF1).	[39]
Cenestin	DMXQS7K	Approved	Cenestin decreases the expression of Insulin-like growth factor I (IGF1).	[24]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Insulin-like growth factor I (IGF1).	[13]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Insulin-like growth factor I (IGF1).	[40]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate decreases the expression of Insulin-like growth factor I (IGF1).	[41]
Curcumin	DMQPH29	Phase 3	Curcumin decreases the expression of Insulin-like growth factor I (IGF1).	[42]
Fenretinide	DMRD5SP	Phase 3	Fenretinide decreases the activity of Insulin-like growth factor I (IGF1).	[43]
Guaiacol	DMN4E7T	Phase 3	Guaiacol decreases the expression of Insulin-like growth factor I (IGF1).	[40]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Insulin-like growth factor I (IGF1).	[40]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Insulin-like growth factor I (IGF1).	[44]
Puerarin	DMJIMXH	Phase 2	Puerarin decreases the expression of Insulin-like growth factor I (IGF1).	[40]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Insulin-like growth factor I (IGF1).	[46]
LY294002	DMY1AFS	Phase 1	LY294002 increases the expression of Insulin-like growth factor I (IGF1).	[47]
Sphingosine-1-Phosphate	DMJCQKA	Phase 1	Sphingosine-1-Phosphate increases the expression of Insulin-like growth factor I (IGF1).	[48]
Glyphosate	DM0AFY7	Investigative	Glyphosate increases the expression of Insulin-like growth factor I (IGF1).	[50]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone increases the expression of Insulin-like growth factor I (IGF1).	[51]
Butanoic acid	DMTAJP7	Investigative	Butanoic acid decreases the expression of Insulin-like growth factor I (IGF1).	[52]
all-trans-4-oxo-retinoic acid	DMM2R1N	Investigative	all-trans-4-oxo-retinoic acid increases the expression of Insulin-like growth factor I (IGF1).	[4]
Cordycepin	DM72Y01	Investigative	Cordycepin affects the expression of Insulin-like growth factor I (IGF1).	[34]
Rutin	DMEHRAJ	Investigative	Rutin decreases the expression of Insulin-like growth factor I (IGF1).	[54]
Maleic Acid	DM4L0R7	Investigative	Maleic Acid increases the expression of Insulin-like growth factor I (IGF1).	[55]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the secretion of Insulin-like growth factor I (IGF1).	[18]
Prednisolone	DMQ8FR2	Approved	Prednisolone decreases the response to substance of Insulin-like growth factor I (IGF1).	[28]
Nifedipine	DMSVOZT	Approved	Nifedipine decreases the response to substance of Insulin-like growth factor I (IGF1).	[37]
Dantrolene	DM1D8XY	Approved	Dantrolene decreases the response to substance of Insulin-like growth factor I (IGF1).	[37]
Rapamycin Immunosuppressant Drug	DM678IB	Investigative	Rapamycin Immunosuppressant Drug increases the response to substance of Insulin-like growth factor I (IGF1).	[53]
EGTA	DMW9MRO	Investigative	EGTA decreases the response to substance of Insulin-like growth factor I (IGF1).	[37]

References

• [1] Intrauterine growth retardation and postnatal growth failure associated with deletion of the insulin-like growth factor I gene. N Engl J Med. 1996 Oct 31;335(18):1363-7. doi: 10.1056/NEJM199610313351805.
• [2] 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.
• [3] 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.
• [4] Retinoic acid and its 4-oxo metabolites are functionally active in human skin cells in vitro. J Invest Dermatol. 2005 Jul;125(1):143-53.
• [5] Toxicogenomics-based prediction of acetaminophen-induced liver injury using human hepatic cell systems. Toxicol Lett. 2016 Jan 5;240(1):50-9.
• [6] 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.
• [7] Mechanism of the divergent effects of estrogen on the cell proliferation of human umbilical endothelial versus aortic smooth muscle cells. Endocrinology. 2007 Dec;148(12):6092-9.
• [8] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [9] Quercetin regulates insulin like growth factor signaling and induces intrinsic and extrinsic pathway mediated apoptosis in androgen independent prostate cancer cells (PC-3). Mol Cell Biochem. 2010 Nov;344(1-2):173-84. doi: 10.1007/s11010-010-0540-4. Epub 2010 Jul 25.
• [10] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [11] Oxidative Stress Alters miRNA and Gene Expression Profiles in Villous First Trimester Trophoblasts. Biomed Res Int. 2015;2015:257090. doi: 10.1155/2015/257090. Epub 2015 Aug 3.
• [12] Role of calcitriol and cortisol on human adipocyte proliferation and oxidative and inflammatory stress: a microarray study. J Nutrigenet Nutrigenomics. 2008;1(1-2):30-48. doi: 10.1159/000109873. Epub 2007 Oct 16.
• [13] DHT and testosterone, but not DHEA or E2, differentially modulate IGF-I, IGFBP-2, and IGFBP-3 in human prostatic stromal cells. Am J Physiol Endocrinol Metab. 2006 May;290(5):E952-60. doi: 10.1152/ajpendo.00451.2005. Epub 2005 Dec 20.
• [14] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [15] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [16] Unique transcriptome, pathways, and networks in the human endometrial fibroblast response to progesterone in endometriosis. Biol Reprod. 2011 Apr;84(4):801-15.
• [17] Dexamethasone administration inhibits skeletal muscle expression of the androgen receptor and IGF-1--implications for steroid-induced myopathy. Clin Endocrinol (Oxf). 2010 Jul;73(1):126-32. doi: 10.1111/j.1365-2265.2009.03683.x. Epub 2009 Aug 4.
• [18] Activation of peroxisome proliferator-activated receptor gamma (PPARgamma) by rosiglitazone suppresses components of the insulin-like growth factor regulatory system in vitro and in vivo. Endocrinology. 2007 Feb;148(2):903-11. doi: 10.1210/en.2006-1121. Epub 2006 Nov 22.
• [19] Prenatal ethanol exposure-induced a low level of foetal blood cholesterol and its mechanism of IGF1-related placental cholesterol transport dysfunction. Toxicology. 2019 Aug 1;424:152237. doi: 10.1016/j.tox.2019.152237. Epub 2019 Jun 18.
• [20] In vitro and in vivo irinotecan-induced changes in expression profiles of cell cycle and apoptosis-associated genes in acute myeloid leukemia cells. Mol Cancer Ther. 2005 Jun;4(6):885-900.
• [21] [Antipsychotic drugs can affect hormone balance. Weight gain, blood lipid disturbances and diabetes are important]. Lakartidningen. 2001 Nov 28;98(48):5462-4, 5467-9.
• [22] Proline-linked nitrosoureas as prolidase-convertible prodrugs in human breast cancer cells. Pharmacol Rep. 2008 Mar-Apr;60(2):171-82.
• [23] 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.
• [24] Estrogens exert route- and dose-dependent effects on insulin-like growth factor (IGF)-binding protein-3 and the acid-labile subunit of the IGF ternary complex. J Clin Endocrinol Metab. 2000 May;85(5):1918-22. doi: 10.1210/jcem.85.5.6527.
• [25] Capsaicin promotes a more aggressive gene expression phenotype and invasiveness in null-TRPV1 urothelial cancer cells. Carcinogenesis. 2011 May;32(5):686-94. doi: 10.1093/carcin/bgr025. Epub 2011 Feb 10.
• [26] Effects of metformin and pioglitazone combination on apoptosis and AMPK/mTOR signaling pathway in human anaplastic thyroid cancer cells. J Biochem Mol Toxicol. 2020 Oct;34(10):e22547. doi: 10.1002/jbt.22547. Epub 2020 Jun 26.
• [27] Thalidomide downregulates angiogenic genes in bone marrow endothelial cells of patients with active multiple myeloma. J Clin Oncol. 2005 Aug 10;23(23):5334-46. doi: 10.1200/JCO.2005.03.723. Epub 2005 Jun 6.
• [28] Anti-TNF antibody treatment improves glucocorticoid induced insulin-like growth factor 1 (IGF1) resistance without influencing myoglobin and IGF1 binding proteins 1 and 3. Ann Rheum Dis. 2006 Mar;65(3):301-5. doi: 10.1136/ard.2005.040816. Epub 2005 Aug 3.
• [29] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [30] Glucocorticoid-activation system mediated glucocorticoid-insulin-like growth factor 1 (GC-IGF1) axis programming alteration of adrenal dysfunction induced by prenatal caffeine exposure. Toxicol Lett. 2019 Mar 1;302:7-17.
• [31] Omics-based responses induced by bosentan in human hepatoma HepaRG cell cultures. Arch Toxicol. 2018 Jun;92(6):1939-1952.
• [32] Serum insulin-like growth factor-I level is independently associated with coronary artery disease progression in young male survivors of myocardial infarction: beneficial effects of bezafibrate treatment. J Am Coll Cardiol. 2000 Mar 1;35(3):647-54. doi: 10.1016/s0735-1097(99)00591-4.
• [33] The differential cancer growth associated with anaesthetics in a cancer xenograft model of mice: mechanisms and implications of postoperative cancer recurrence. Cell Biol Toxicol. 2023 Aug;39(4):1561-1575. doi: 10.1007/s10565-022-09747-9. Epub 2022 Aug 12.
• [34] Adenosine and Cordycepin Accelerate Tissue Remodeling Process through Adenosine Receptor Mediated Wnt/-Catenin Pathway Stimulation by Regulating GSK3b Activity. Int J Mol Sci. 2021 May 25;22(11):5571. doi: 10.3390/ijms22115571.
• [35] Low-expressional IGF1 mediated methimazole-induced liver developmental toxicity in fetal mice. Toxicology. 2018 Sep 1;408:70-79. doi: 10.1016/j.tox.2018.07.004. Epub 2018 Jul 7.
• [36] Effects of estriol on proliferative activity and expression of insulin-like growth factor-I (IGF-I) and IGF-I receptor mRNA in cultured human osteoblast-like osteosarcoma cells. Gynecol Endocrinol. 2005 Jan;20(1):6-12. doi: 10.1080/09513590400020831.
• [37] Insulin-like growth factors (IGF) I and II utilize different calcium signaling pathways in a primary human parathyroid cell culture model. World J Surg. 2006 Mar;30(3):333-45. doi: 10.1007/s00268-005-0339-8.
• [38] Luteinizing Hormone-Releasing Hormone (LHRH)-I antagonist cetrorelix inhibits myeloma cell growth in vitro and in vivo. Mol Cancer Ther. 2011 Jan;10(1):148-58. doi: 10.1158/1535-7163.MCT-10-0829. Epub 2010 Nov 9.
• [39] Pharmacokinetics, pharmacodynamics, and safety of microencapsulated octreotide acetate in healthy subjects. J Clin Pharmacol. 2000 May;40(5):475-81. doi: 10.1177/00912700022009242.
• [40] Examining the genomic influence of skin antioxidants in vitro. Mediators Inflamm. 2010;2010.
• [41] (-)-Epigallocatechin gallate inhibits growth and activation of the VEGF/VEGFR axis in human colorectal cancer cells. Chem Biol Interact. 2010 May 14;185(3):247-52. doi: 10.1016/j.cbi.2010.03.036. Epub 2010 Mar 25.
• [42] Novel carbocyclic curcumin analog CUR3d modulates genes involved in multiple apoptosis pathways in human hepatocellular carcinoma cells. Chem Biol Interact. 2015 Dec 5;242:107-22.
• [43] Induction of apoptosis in primary meningioma cultures by fenretinide. Cancer Res. 2005 Feb 15;65(4):1547-53. doi: 10.1158/0008-5472.CAN-04-0786.
• [44] Histone acetylation-mediated regulation of the Hippo pathway. PLoS One. 2013 May 6;8(5):e62478. doi: 10.1371/journal.pone.0062478. Print 2013.
• [45] 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.
• [46] The BET bromodomain inhibitor JQ1 suppresses growth of pancreatic ductal adenocarcinoma in patient-derived xenograft models. Oncogene. 2016 Feb 18;35(7):833-45.
• [47] l-Ascorbic acid 2-phosphate promotes elongation of hair shafts via the secretion of insulin-like growth factor-1 from dermal papilla cells through phosphatidylinositol 3-kinase. Br J Dermatol. 2009 Jun;160(6):1157-62. doi: 10.1111/j.1365-2133.2009.09108.x. Epub 2009 Mar 26.
• [48] Arsenic requires sphingosine-1-phosphate type 1 receptors to induce angiogenic genes and endothelial cell remodeling. Am J Pathol. 2009 May;174(5):1949-58. doi: 10.2353/ajpath.2009.081016. Epub 2009 Apr 6.
• [49] 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.
• [50] Use of human neuroblastoma SH-SY5Y cells to evaluate glyphosate-induced effects on oxidative stress, neuronal development and cell death signaling pathways. Environ Int. 2020 Feb;135:105414. doi: 10.1016/j.envint.2019.105414. Epub 2019 Dec 23.
• [51] p,p'-Dichlorodiphenyltrichloroethane (p,p'-DDT) and p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) repress prostate specific antigen levels in human prostate cancer cell lines. Chem Biol Interact. 2015 Mar 25;230:40-9. doi: 10.1016/j.cbi.2015.02.002. Epub 2015 Feb 12.
• [52] MS4A3-HSP27 target pathway reveals potential for haematopoietic disorder treatment in alimentary toxic aleukia. Cell Biol Toxicol. 2023 Feb;39(1):201-216. doi: 10.1007/s10565-021-09639-4. Epub 2021 Sep 28.
• [53] Mammalian target of rapamycin inhibitors activate the AKT kinase in multiple myeloma cells by up-regulating the insulin-like growth factor receptor/insulin receptor substrate-1/phosphatidylinositol 3-kinase cascade. Mol Cancer Ther. 2005 Oct;4(10):1533-40. doi: 10.1158/1535-7163.MCT-05-0068.
• [54] Regulation of IGF-I production and proliferation of human leiomyomal smooth muscle cells by Scutellaria barbata D. Don in vitro: isolation of flavonoids of apigenin and luteolin as acting compounds. Toxicol Appl Pharmacol. 2005 Jun 15;205(3):213-24. doi: 10.1016/j.taap.2004.10.007.
• [55] Profiling transcriptomes of human SH-SY5Y neuroblastoma cells exposed to maleic acid. PeerJ. 2017 Apr 5;5:e3175.
• [56] Genome-wide association analyses suggest NELL1 influences adverse metabolic response to HCTZ in African Americans. Pharmacogenomics J. 2014 Feb;14(1):35-40. doi: 10.1038/tpj.2013.3. Epub 2013 Feb 12.
• [57] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
• [58] Controlled dimerization of insulin-like growth factor-1 and insulin receptors reveals shared and distinct activities of holo and hybrid receptors. J Biol Chem. 2018 Mar 9;293(10):3700-3709. doi: 10.1074/jbc.M117.789503. Epub 2018 Jan 12.
• [59] Inhibition of insulin-like growth factor-I responses in MCF-7 cells by 2,3,7,8-tetrachlorodibenzo-p-dioxin and related compounds. Mol Cell Endocrinol. 1992 Sep;87(1-3):19-28. doi: 10.1016/0303-7207(92)90229-y.