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

General Information of Drug (ID: DMUP5Z0)

Drug Name

Nirogacestat Drug Info

Synonyms

PF-03084014; 1290543-63-3; PF-03084014; PF-3084014; UNII-QZ62892OFJ; 865773-15-5; PF 3084014; PF-03084014 (PF-3084014); QZ62892OFJ; Z-3181; PF03084014; Nirogacestat [USAN]; Nirogacestat (USAN/INN); GTPL7746; SCHEMBL13184754; CHEMBL1770916; EX-A855; DTXSID60235679; MolPort-039-193-852; (2S)-2-[[(2S)-6,8-difluoro-1,2,3,4-tetrahydronaphthalen-2-yl]amino]-N-[1-[1-(2,2-dimethylpropylamino)-2-methylpropan-2-yl]imidazol-4-yl]pentanamide; ZINC38217837; s8018; AKOS030526383; SB16726; DB12005; CS-1689; NCGC00378713-01

Indication

Disease Entry	ICD 11	Status	REF
Desmoid tumour	2F7C	Approved	[1]
Alzheimer disease	8A20	Phase 2	[2]
Solid tumour/cancer	2A00-2F9Z	Phase 2	[3]

Cross-matching ID

PubChem CID: 46224413
CAS Number: CAS 1290543-63-3
TTD Drug ID: DMUP5Z0

Molecule-Related Drug Atlas

Molecule Type:

DTT

DOT

Drug Status:

Approved Drug(s)

Clinical Trial Drug(s)

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Drug(s) Targeting Amyloid beta A4 protein (APP)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Aducanumab	DM51JW4	Alzheimer disease	8A20	Approved	[6]
Lecanemab	DMW03YD	Alzheimer disease	8A20	Approved	[7]
Florbetapir F-18	DMJ8A3Z	Diagnostic imaging	N.A.	Approved	[8]
GV-971	DMTMA5W	Alzheimer disease	8A20	Approved in China	[9]
Curcumin	DMQPH29	Solid tumour/cancer	2A00-2F9Z	Phase 3	[10]
Solanezumab	DM0HIU5	Alzheimer disease	8A20	Phase 3	[11]
Tramiprosate	DM7BSRH	Alzheimer disease	8A20	Phase 3	[12]
Bapineuzumab	DMHQ5GK	Alzheimer disease	8A20	Phase 3	[13]
ALZT-OP1	DMG5BTD	Alzheimer disease	8A20	Phase 3	[14]
Gantenerumab	DMWX90U	Alzheimer disease	8A20	Phase 3	[15]
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Drug(s) Targeting Gamma-secretase (GS)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
(S)-FLURBIPROFEN	DMF2O4T	Myalgia	FB56.2	Preregistration	[16]
AMG 386	DMQJXL4	Breast cancer	2C60-2C65	Phase 3	[17]
Semagacestat	DML83IW	Parkinson disease	8A00.0	Phase 3	[18]
R-flurbiprofen	DMFIVSR	N. A.	N. A.	Phase 2	[16]
MK-0752	DMLTAES	Alzheimer disease	8A20	Phase 2	[19]
BMS-708163	DM51LTG	Alzheimer disease	8A20	Phase 2	[20]
CHF-5074	DMTE071	Alzheimer disease	8A20	Phase 2	[21]
RO-4929097	DMXA6B3	Breast cancer	2C60-2C65	Phase 2	[22]
AL102	DMCTWIB	Desmoid tumour	2F7C	Phase 2	[23]
SPI-014	DM5IPUS	Alzheimer disease	8A20	Phase 1	[24]
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Drug(s) Affected By Myc proto-oncogene protein (MYC)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[25]
Sertraline	DM0FB1J	Coronary heart disease	BA80.Z	Approved	[26]
Fulvestrant	DM0YZC6	Breast cancer	2C60-2C65	Approved	[27]
Gefitinib	DM15F0X	Colon adenocarcinoma		Approved	[28]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[29]
Selenium	DM25CGV	N. A.	N. A.	Approved	[30]
Ribavirin	DMEYLH9	Hepatitis C virus infection	1E51.1	Approved	[31]
Trametinib	DM2JGQ3	Melanoma	2C30	Approved	[32]
Sulindac	DM2QHZU	Acute myelogenous leukaemia	2A41	Approved	[33]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[34]
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Drug(s) Affected By Poly polymerase 1 (PARP1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[35]
Gefitinib	DM15F0X	Colon adenocarcinoma		Approved	[36]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[37]
Nitric Oxide	DM1RBYG	Hypertension	BA00-BA04	Approved	[38]
Citalopram	DM2G9AE	Acute coronary syndrome	BA41	Approved	[39]
Ciprofloxacin XR	DM2NLS9	Acute gonococcal cervicitis		Approved	[40]
Imipramine	DM2NUH3	Depression	6A70-6A7Z	Approved	[39]
Colchicine	DM2POTE	Acute gout flare	FA25.0	Approved	[41]
Sulindac	DM2QHZU	Acute myelogenous leukaemia	2A41	Approved	[42]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[43]
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Drug(s) Affected By Transcription factor HES-1 (HES1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[44]
Selenium	DM25CGV	N. A.	N. A.	Approved	[45]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[46]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[47]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[48]
Testosterone	DM7HUNW	Hot flushes	GA30	Approved	[49]
Calcitriol	DM8ZVJ7	Congenital alopecia	LC30	Approved	[50]
Leflunomide	DMR8ONJ	Arthritis	FA20	Approved	[51]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[52]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[53]
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Molecular Interaction Atlas of This Drug

Molecular Interaction Atlas

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Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Gamma-secretase (GS)	TT9W8GU	APH1A_HUMAN; APH1B_HUMAN; PEN2_HUMAN; NICA_HUMAN; PSN1_HUMAN	Modulator	[4]
Amyloid beta A4 protein (APP)	TTE4KHA	A4_HUMAN	Inhibitor	[3]

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Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Myc proto-oncogene protein (MYC)	OTPV5LUK	MYC_HUMAN	Gene/Protein Processing	[5]
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Protein Interaction/Cellular Processes	[5]
Transcription factor HES-1 (HES1)	OT8P19W2	HES1_HUMAN	Gene/Protein Processing	[5]

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References

1	FDA Approved Drug Products from FDA Official Website. 2023. Application Number: 217677
2	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: 7746).
3	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
4	Pharmacodynamics and pharmacokinetics of the gamma-secretase inhibitor PF-3084014.J Pharmacol Exp Ther.2010 Jul;334(1):269-77.
5	NOTCH signaling is activated in and contributes to resistance in enzalutamide-resistant prostate cancer cells. J Biol Chem. 2019 May 24;294(21):8543-8554. doi: 10.1074/jbc.RA118.006983. Epub 2019 Apr 2.
6	Passive anti-amyloid immunotherapy in Alzheimer's disease: What are the most promising targets . Immun Ageing. 2013; 10: 18.
7	The murine version of BAN2401 (mAb158) selectively reduces amyloid-beta protofibrils in brain and cerebrospinal fluid of tg-ArcSwe mice. J Alzheimers Dis. 2015;43(2):575-88.
8	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
9	Sodium oligomannate therapeutically remodels gut microbiota and suppresses gut bacterial amino acids-shaped neuroinflammation to inhibit Alzheimer's disease progression. Cell Res. 2019 Oct;29(10):787-803.
10	Curcumin and dehydrozingerone derivatives: synthesis, radiolabeling, and evaluation for beta-amyloid plaque imaging. J Med Chem. 2006 Oct 5;49(20):6111-9.
11	Phase 3 trials of solanezumab for mild-to-moderate Alzheimer's disease. N Engl J Med. 2014 Jan 23;370(4):311-21.
12	Targeting soluble Abeta peptide with Tramiprosate for the treatment of brain amyloidosis. Neurobiol Aging. 2007 Apr;28(4):537-47.
13	Bapineuzumab: anti-beta-amyloid monoclonal antibodies for the treatment of Alzheimer's disease. Immunotherapy. 2010 Nov;2(6):767-82.
14	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
15	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
16	The geminal dimethyl analogue of Flurbiprofen as a novel Abeta42 inhibitor and potential Alzheimer's disease modifying agent. Bioorg Med Chem Lett. 2006 Apr 15;16(8):2219-23.
17	Clinical pipeline report, company report or official report of Roche (2009).
18	A phase 3 trial of semagacestat for treatment of Alzheimer's disease. N Engl J Med. 2013 Jul 25;369(4):341-50.
19	Determination of the gamma-secretase inhibitor MK-0752 in human plasma by online extraction and electrospray tandem mass spectrometry (HTLC-ESI-MS/MS). J Chromatogr B Analyt Technol Biomed Life Sci. 2010 Sep 1;878(25):2348-52.
20	Safety and tolerability of the gamma-secretase inhibitor avagacestat in a phase 2 study of mild to moderate Alzheimer disease. Arch Neurol. 2012 Nov;69(11):1430-40.
21	CHF5074, a novel gamma-secretase modulator, attenuates brain beta-amyloid pathology and learning deficit in a mouse model of Alzheimer's disease.Br J Pharmacol.2009 Mar;156(6):982-93.
22	Phase I study of RO4929097, a gamma secretase inhibitor of Notch signaling, in patients with refractory metastatic or locally advanced solid tumors. J Clin Oncol. 2012 Jul 1;30(19):2348-53.
23	Clinical pipeline report, company report or official report of Ayala Pharmaceuticals.
24	Modulation of gamma-secretase for the treatment of Alzheimer's disease. Int J Alzheimers Dis. 2012;2012:210756.
25	Acetaminophen-induced proliferation of estrogen-responsive breast cancer cells is associated with increases in c-myc RNA expression and NF-kappaB activity. Toxicol Sci. 2002 Apr;66(2):233-43. doi: 10.1093/toxsci/66.2.233.
26	Sertraline induces endoplasmic reticulum stress in hepatic cells. Toxicology. 2014 Aug 1;322:78-88. doi: 10.1016/j.tox.2014.05.007. Epub 2014 May 24.
27	Estrogen regulation in human breast cancer cells of new downstream gene targets involved in estrogen metabolism, cell proliferation and cell transformation. J Mol Endocrinol. 2004 Apr;32(2):397-414.
28	ZD1839 induces p15INK4b and causes G1 arrest by inhibiting the mitogen-activated protein kinase/extracellular signal-regulated kinase pathway. Mol Cancer Ther. 2007 May;6(5):1579-87. doi: 10.1158/1535-7163.MCT-06-0814.
29	Arsenic suppresses gene expression in promyelocytic leukemia cells partly through Sp1 oxidation. Blood. 2005 Jul 1;106(1):304-10.
30	Selenite and selenomethionine promote HL-60 cell cycle progression. J Nutr. 2002 Apr;132(4):674-9. doi: 10.1093/jn/132.4.674.
31	Ribavirin augments doxorubicin's efficacy in human hepatocellular carcinoma through inhibiting doxorubicin-induced eIF4E activation. J Biochem Mol Toxicol. 2018 Jan;32(1). doi: 10.1002/jbt.22007. Epub 2017 Nov 7.
32	Combination small molecule MEK and PI3K inhibition enhances uveal melanoma cell death in a mutant GNAQ- and GNA11-dependent manner. Clin Cancer Res. 2012 Aug 15;18(16):4345-55. doi: 10.1158/1078-0432.CCR-11-3227. Epub 2012 Jun 25.
33	Novel detection and differential utilization of a c-myc transcriptional block in colon cancer chemoprevention. Cancer Res. 2002 Nov 1;62(21):6006-10.
34	The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
35	Cannabidiol enhances cytotoxicity of anti-cancer drugs in human head and neck squamous cell carcinoma. Sci Rep. 2020 Nov 26;10(1):20622. doi: 10.1038/s41598-020-77674-y.
36	Evidence of securin-mediated resistance to gefitinib-induced apoptosis in human cancer cells. Chem Biol Interact. 2013 Apr 25;203(2):412-22. doi: 10.1016/j.cbi.2013.03.011. Epub 2013 Mar 22.
37	Cigarette smoke and asbestos activate poly-ADP-ribose polymerase in alveolar epithelial cells. J Investig Med. 2001 Jan;49(1):68-76. doi: 10.2310/6650.2001.34092.
38	Apoptotic signaling pathways induced by nitric oxide in human lymphoblastoid cells expressing wild-type or mutant p53. Cancer Res. 2004 May 1;64(9):3022-9. doi: 10.1158/0008-5472.can-03-1880.
39	The antidepressants imipramine, clomipramine, and citalopram induce apoptosis in human acute myeloid leukemia HL-60 cells via caspase-3 activation. J Biochem Mol Toxicol. 1999;13(6):338-47. doi: 10.1002/(sici)1099-0461(1999)13:6<338::aid-jbt8>3.0.co;2-7.
40	Ciprofloxacin mediated cell growth inhibition, S/G2-M cell cycle arrest, and apoptosis in a human transitional cell carcinoma of the bladder cell line. Clin Cancer Res. 2000 Mar;6(3):891-900.
41	Investigation of molecular mechanisms underlying the antiproliferative effects of colchicine against PC3 prostate cancer cells. Toxicol In Vitro. 2021 Jun;73:105138. doi: 10.1016/j.tiv.2021.105138. Epub 2021 Mar 6.
42	Sulindac enhances adenoviral vector expressing mda-7/IL-24-mediated apoptosis in human lung cancer. Mol Cancer Ther. 2005 Feb;4(2):291-304.
43	Methotrexate induces poly(ADP-ribose) polymerase-dependent, caspase 3-independent apoptosis in subsets of proliferating CD4+ T cells. Clin Exp Immunol. 2007 May;148(2):288-95. doi: 10.1111/j.1365-2249.2007.03335.x. Epub 2007 Feb 7.
44	Modulation of notch signaling pathway to prevent H2O2/menadione-induced SK-N-MC cells death by EUK134. Cell Mol Neurobiol. 2014 Oct;34(7):1037-45. doi: 10.1007/s10571-014-0079-0. Epub 2014 Jul 9.
45	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.
46	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.
47	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.
48	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.
49	The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
50	Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
51	Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
52	Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
53	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.