Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DMM9F25)

• Drug Name: LDE225 Drug Info
• Synonyms: Erismodegib

Indication

Disease Entry	ICD 11	Status	REF
Basal cell carcinoma	2C32	Approved	[1]
Medulloblastoma	2A00.10	Phase 2	[2]
Skin cancer	2C30-2C37	Phase 2	[3]

• Cross-matching ID:
  PubChem CID: 24775005
  ChEBI ID: CHEBI:90863
  CAS Number: CAS 956697-53-3
  TTD Drug ID: DMM9F25

Molecule-Related Drug Atlas

Drug(s) Targeting Smoothened homolog (SMO)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PF-04449913	DMSB068	Chronic myelomonocytic leukaemia	2A40	Approved	[6]
Vismodegib	DM5IXKQ	Basal cell carcinoma	2C32	Approved	[7]
LY2940680	DMTJWIQ	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[6]
BMS-833923	DM459Q7	Solid tumour/cancer	2A00-2F9Z	Phase 1b	[8]
LEQ-506	DM5INZP	Solid tumour/cancer	2A00-2F9Z	Phase 1	[9]
TAK-441	DM7DFBL	Solid tumour/cancer	2A00-2F9Z	Phase 1	[10]
PMID25726713-Compound-49	DM2CT4G	N. A.	N. A.	Patented	[11]
PMID25726713-Compound-51	DMF0OW4	N. A.	N. A.	Patented	[11]
PMID25726713-Compound-48	DMSIOUA	N. A.	N. A.	Patented	[11]
PMID25726713-Compound-47	DMXE5KM	N. A.	N. A.	Patented	[11]

Drug(s) Affected By Suppressor of fused homolog (SUFU)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Quercetin	DM3NC4M	Obesity	5B81	Approved	[12]
Marinol	DM70IK5	Anorexia nervosa cachexia	6B80	Approved	[13]
Cupric Sulfate	DMP0NFQ	Fungal infection	1F29-1F2F	Approved	[14]
Arsenic	DMTL2Y1	N. A.	N. A.	Approved	[15]
Fluorouracil	DMUM7HZ	Adenocarcinoma	2D40	Approved	[16]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[17]
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[18]
Vismodegib	DM5IXKQ	Basal cell carcinoma	2C32	Approved	[5]
Urethane	DM7NSI0	N. A.	N. A.	Phase 4	[19]
Benzo(a)pyrene	DMN7J43	N. A.	N. A.	Phase 1	[20]

Drug(s) Affected By Zinc finger protein GLI2 (GLI2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Selenium	DM25CGV	N. A.	N. A.	Approved	[21]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[22]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[23]
Vismodegib	DM5IXKQ	Basal cell carcinoma	2C32	Approved	[24]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[25]
Marinol	DM70IK5	Anorexia nervosa cachexia	6B80	Approved	[13]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[26]
Temozolomide	DMKECZD	Adenocarcinoma	2D40	Approved	[27]
Dexamethasone	DMMWZET	Acute adrenal insufficiency		Approved	[28]
Decitabine	DMQL8XJ	Acute myelogenous leukaemia	2A41	Approved	[29]

Drug(s) Affected By N-myc proto-oncogene protein (MYCN)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[30]
Pantothenic acid	DM091H2	Vitamin deficiency	5B55-5B71	Approved	[31]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[32]
Isotretinoin	DM4QTBN	Acne vulgaris	ED80	Approved	[33]
Panobinostat	DM58WKG	Chronic graft versus host disease		Approved	[34]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[35]
LY2835219	DM93VBZ	Breast cancer	2C60-2C65	Approved	[36]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[37]
Emetine	DMCT2YF	Hepatitis virus infection	1E50-1E51	Approved	[38]
Menthol	DMG2KW7	Back pain	ME84.Z	Approved	[39]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Smoothened homolog (SMO)	TT8J1S3	SMO_HUMAN	Modulator	[4]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
N-myc proto-oncogene protein (MYCN)	OTWD33K1	MYCN_HUMAN	Drug Response	[5]
Suppressor of fused homolog (SUFU)	OT0IRYG1	SUFU_HUMAN	Drug Response	[5]
Zinc finger protein GLI2 (GLI2)	OTIRV97L	GLI2_HUMAN	Drug Response	[5]

References

• [1] The 12-month analysis from Basal Cell Carcinoma Outcomes with LDE225 Treatment (BOLT): A phase II, randomized, double-blind study of sonidegib in patients with advanced basal cell carcinoma. J Am Acad Dermatol. 2016 Jul;75(1):113-125.e5.
• [2] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [3] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 8199).
• [4] Inhibition of Hedgehog signalling by NVP-LDE225 (Erismodegib) interferes with growth and invasion of human renal cell carcinoma cells. Br J Cancer. 2014 Sep 9;111(6):1168-79.
• [5] Epigenetic targeting of Hedgehog pathway transcriptional output through BET bromodomain inhibition. Nat Med. 2014 Jul;20(7):732-40. doi: 10.1038/nm.3613. Epub 2014 Jun 29.
• [6] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
• [7] Nat Rev Drug Discov. 2013 Feb;12(2):87-90.
• [8] Clinical pipeline report, company report or official report of Exelixis (2011).
• [9] Discovery of NVP-LEQ506, a second-generation inhibitor of smoothened. ChemMedChem. 2013 Aug;8(8):1261-5.
• [10] TAK-441, a novel investigational smoothened antagonist, delays castration-resistant progression in prostate cancer by disrupting paracrine hedgehog signaling. Int J Cancer. 2013 Oct 15;133(8):1955-66.
• [11] Hedgehog inhibitors: a patent review (2013 - present).Expert Opin Ther Pat. 2015 May;25(5):549-65.
• [12] 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.
• [13] 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.
• [14] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [15] Epigenetic changes in individuals with arsenicosis. Chem Res Toxicol. 2011 Feb 18;24(2):165-7. doi: 10.1021/tx1004419. Epub 2011 Feb 4.
• [16] Down-regulation of Sonic hedgehog signaling pathway activity is involved in 5-fluorouracil-induced apoptosis and motility inhibition in Hep3B cells. Acta Biochim Biophys Sin (Shanghai). 2008 Sep;40(9):819-29.
• [17] Analysis of estrogen agonism and antagonism of tamoxifen, raloxifene, and ICI182780 in endometrial cancer cells: a putative role for the epidermal growth factor receptor ligand amphiregulin. J Soc Gynecol Investig. 2005 Oct;12(7):e55-67.
• [18] 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.
• [19] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [20] 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.
• [21] 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.
• [22] Quercetin suppresses pancreatic ductal adenocarcinoma progression via inhibition of SHH and TGF-/Smad signaling pathways. Cell Biol Toxicol. 2021 Jun;37(3):479-496. doi: 10.1007/s10565-020-09562-0. Epub 2020 Oct 17.
• [23] 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.
• [24] Hedgehog signaling antagonist GDC-0449 (Vismodegib) inhibits pancreatic cancer stem cell characteristics: molecular mechanisms. PLoS One. 2011;6(11):e27306. doi: 10.1371/journal.pone.0027306. Epub 2011 Nov 8.
• [25] Arsenic trioxide prevents osteosarcoma growth by inhibition of GLI transcription via DNA damage accumulation. PLoS One. 2013 Jul 8;8(7):e69466. doi: 10.1371/journal.pone.0069466. Print 2013.
• [26] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [27] 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.
• [28] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [29] DNA methylation inhibits p53-mediated survivin repression. Oncogene. 2009 May 14;28(19):2046-50. doi: 10.1038/onc.2009.62. Epub 2009 Apr 13.
• [30] Role of miRNA in the regulation of cannabidiol-mediated apoptosis in neuroblastoma cells. Oncotarget. 2019 Jan 1;10(1):45-59. doi: 10.18632/oncotarget.26534. eCollection 2019 Jan 1.
• [31] Calcium pantothenate modulates gene expression in proliferating human dermal fibroblasts. Exp Dermatol. 2009 Nov;18(11):969-78. doi: 10.1111/j.1600-0625.2009.00884.x. Epub 2009 Apr 8.
• [32] All-trans-retinoic acid inhibits collapsin response mediator protein-2 transcriptional activity during SH-SY5Y neuroblastoma cell differentiation. FEBS J. 2007 Jan;274(2):498-511. doi: 10.1111/j.1742-4658.2006.05597.x.
• [33] Molecular targeting of retinoic acid metabolism in neuroblastoma: the role of the CYP26 inhibitor R116010 in vitro and in vivo. Br J Cancer. 2007 Jun 4;96(11):1675-83.
• [34] 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.
• [35] [Impact of arsenic trioxide on proliferation and metastasis of drug-resistant human ovarian carcinoma cell line]. Ai Zheng. 2002 Aug;21(8):863-7.
• [36] Biological specificity of CDK4/6 inhibitors: dose response relationship, in vivo signaling, and composite response signature. Oncotarget. 2017 Jul 4;8(27):43678-43691. doi: 10.18632/oncotarget.18435.
• [37] 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.
• [38] IGF2BP1 induces neuroblastoma via a druggable feedforward loop with MYCN promoting 17q oncogene expression. Mol Cancer. 2023 May 29;22(1):88. doi: 10.1186/s12943-023-01792-0.
• [39] 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.