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

General Information of Drug (ID: DMPF2N1)

• Drug Name: paxilline Drug Info
• Synonyms: 4b-Hydroxy-2-(1-hydroxy-1-methylethyl)-12b,12c-dimethyl-5,6,6a,7,12,12b,12c,13,14,14a-decahydro-2H-chromeno[5',6':6,7]indeno[1,2-b]indol-3(4bH)-one; paxillin; AC1L1IR1; GTPL2309; BDBM86263; CTK7H1286; ACNHBCIZLNNLRS-UHFFFAOYSA-N; NCGC00168476-01; CAS_57186-25-1; hydroxy-(1-hydroxy-1-methyl-ethyl)-dimethyl-[ ]one; 4b-Hydroxy-2-(1-hydroxy-1-methylethyl)-12b,12c-dimethyl-5,6,6a,7,12,12b,12c,13,14,14a-decahydro-2H-chromeno[5',6':6,7]indeno[1,2-b]indol-3(4bh)-one #

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1]

• Cross-matching ID:
  PubChem CID: 105008
  ChEBI ID: CHEMBL410063
  CAS Number: CAS 57186-25-1
  TTD Drug ID: DMPF2N1

Molecule-Related Drug Atlas

Drug(s) Targeting Oxysterols receptor LXR-alpha (NR1H3)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
US9073931, E2	DMK9FJG	N. A.	N. A.	Patented	[5]
BDBM50177019	DMEL28G	N. A.	N. A.	Patented	[6]
US9006244, E2b	DMP0TBO	N. A.	N. A.	Patented	[7]
US9073931, E1	DM2Z43I	N. A.	N. A.	Patented	[5]
US9006244, E1	DMBF1C0	N. A.	N. A.	Patented	[7]
BDBM50177012	DM52IQF	N. A.	N. A.	Patented	[6]
US9006244, E2a	DMPDF9B	N. A.	N. A.	Patented	[7]
67S	DMJL1MB	N. A.	N. A.	Patented	[6]
US9073931, E3	DMCYM8P	N. A.	N. A.	Patented	[5]
desmosterol	DMV8SUM	Discovery agent	N.A.	Investigative	[8]

Drug(s) Targeting Charybdotoxin receptor beta-4 (BKbeta4)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
BMS-223131	DMJUV6C	Erectile dysfunction	HA01.1	Phase 2	[9]
NS-1619	DMES0OT	Asthma	CA23	Terminated	[10]
CNS-1237	DMP3QAZ	Cerebrovascular ischaemia	8B1Z	Terminated	[11]
[14C]TEA	DM6SFYH	Discovery agent	N.A.	Investigative	[12]
iberiotoxin	DMRIG3O	Discovery agent	N.A.	Investigative	[12]
slotoxin	DMBD6TC	Discovery agent	N.A.	Investigative	[13]

Drug(s) Affected By Stearoyl-CoA desaturase (SCD)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Clavulanate	DM2FGRT	Bacteremia	1A73	Approved	[14]
Citalopram	DM2G9AE	Acute coronary syndrome	BA41	Approved	[15]
Imipramine	DM2NUH3	Depression	6A70-6A7Z	Approved	[15]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[16]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[17]
Rofecoxib	DM3P5DA	Osteoarthritis	FA00-FA05	Approved	[18]
Fluoxetine	DM3PD2C	Bipolar depression		Approved	[15]
Fructose	DM43AN2	Vomiting	MD90	Approved	[19]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[20]
Bupropion	DM5PCS7	Depression	6A70-6A7Z	Approved	[15]

Drug(s) Affected By Nuclear receptor-interacting protein 1 (NRIP1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Fulvestrant	DM0YZC6	Breast cancer	2C60-2C65	Approved	[21]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[22]
Panobinostat	DM58WKG	Chronic graft versus host disease		Approved	[23]
Calcitriol	DM8ZVJ7	Congenital alopecia	LC30	Approved	[24]
Leflunomide	DMR8ONJ	Arthritis	FA20	Approved	[25]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[26]
Clorgyline	DMCEUJD	Parkinson disease	8A00.0	Approved	[27]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[28]
Rosiglitazone	DMILWZR	Chronic kidney disease	GB61	Approved	[29]
Teniposide	DMLW57T	Acute lymphoblastic leukaemia	2A85	Approved	[30]

Drug(s) Affected By Nuclear receptor subfamily 0 group B member 2 (NR0B2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Calcipotriol	DM03CP7	Psoriasis	EA90	Approved	[31]
Sertraline	DM0FB1J	Coronary heart disease	BA80.Z	Approved	[32]
Fulvestrant	DM0YZC6	Breast cancer	2C60-2C65	Approved	[21]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[33]
Clavulanate	DM2FGRT	Bacteremia	1A73	Approved	[14]
Imipramine	DM2NUH3	Depression	6A70-6A7Z	Approved	[32]
Thioridazine	DM35M8J	Schizophrenia	6A20	Approved	[34]
Deoxycholic acid	DM3GYAL	Subcutaneous fat disorder	EF02	Approved	[35]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[17]
Fluoxetine	DM3PD2C	Bipolar depression		Approved	[32]

Drug(s) Affected By Carbohydrate-responsive element-binding protein (MLXIPL)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[36]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[28]
Dexamethasone	DMMWZET	Acute adrenal insufficiency		Approved	[37]
Cupric Sulfate	DMP0NFQ	Fungal infection	1F29-1F2F	Approved	[38]
Decitabine	DMQL8XJ	Acute myelogenous leukaemia	2A41	Approved	[39]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[40]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[41]
Triclosan	DMZUR4N	Malaria	1F40-1F45	Approved	[42]
Urethane	DM7NSI0	N. A.	N. A.	Phase 4	[43]
SNDX-275	DMH7W9X	Breast cancer	2C60-2C65	Phase 3	[23]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Charybdotoxin receptor beta-4 (BKbeta4)	TT1AQ50	KCMB4_HUMAN	Blocker (channel blocker)	[2]
Oxysterols receptor LXR-alpha (NR1H3)	TTECBXN	NR1H3_HUMAN	Agonist	[3]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Carbohydrate-responsive element-binding protein (MLXIPL)	OTR9MLLW	MLXPL_HUMAN	Gene/Protein Processing	[4]
Nuclear receptor subfamily 0 group B member 2 (NR0B2)	OT7UVICX	NR0B2_HUMAN	Gene/Protein Processing	[4]
Nuclear receptor-interacting protein 1 (NRIP1)	OTIZOJQV	NRIP1_HUMAN	Gene/Protein Processing	[4]
Stearoyl-CoA desaturase (SCD)	OTB1073G	SCD_HUMAN	Gene/Protein Processing	[4]

References

• [1] 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: 2309).
• [2] Paxilline inhibition of the alpha-subunit of the high-conductance calcium-activated potassium channel. Neuropharmacology. 1996;35(7):963-8.
• [3] A natural product ligand of the oxysterol receptor, liver X receptor. J Pharmacol Exp Ther. 2003 Oct;307(1):291-6.
• [4] Combinations of LXR and RXR agonists induce triglyceride accumulation in human HepaRG cells in a synergistic manner. Arch Toxicol. 2020 Apr;94(4):1303-1320. doi: 10.1007/s00204-020-02685-7. Epub 2020 Mar 2.
• [5] Liver X receptor modulators. US9073931.
• [6] Piperazine derivatives as liver X receptor modulators. US10144715.
• [7] Liver X receptor modulators. US9006244.
• [8] Sterol intermediates from cholesterol biosynthetic pathway as liver X receptor ligands. J Biol Chem. 2006 Sep 22;281(38):27816-26.
• [9] Effect of 4-(5-chloro-2-hydroxyphenyl)-3-(2-hydroxyethyl)-6-(trifluoromethyl)-quinolin-2(1H)-one (BMS-223131), a novel opener of large conductance ... J Pharmacol Exp Ther. 2005 May;313(2):840-7.
• [10] BK channel activation by NS-1619 is partially mediated by intracellular Ca2+ release in smooth muscle cells of porcine coronary artery
• [11] Effects of Ca2+ and Na+ channel inhibitors in vitro and in global cerebral ischaemia in vivo. Eur J Pharmacol. 1997 Aug 6;332(2):121-31.
• [12] 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. (Target id: 380).
• [13] Slotoxin, alphaKTx1.11, a new scorpion peptide blocker of MaxiK channels that differentiates between alpha and alpha+beta (beta1 or beta4) complexes. FEBS Lett. 2001 Sep 21;505(3):369-73.
• [14] Molecular mechanisms of hepatotoxic cholestasis by clavulanic acid: Role of NRF2 and FXR pathways. Food Chem Toxicol. 2021 Dec;158:112664. doi: 10.1016/j.fct.2021.112664. Epub 2021 Nov 9.
• [15] Antidepressant drugs activate SREBP and up-regulate cholesterol and fatty acid biosynthesis in human glial cells. Neurosci Lett. 2006 Mar 13;395(3):185-90. doi: 10.1016/j.neulet.2005.10.096. Epub 2005 Dec 1.
• [16] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
• [17] 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.
• [18] Rofecoxib modulates multiple gene expression pathways in a clinical model of acute inflammatory pain. Pain. 2007 Mar;128(1-2):136-47.
• [19] Effects of four-week high-fructose diet on gene expression in skeletal muscle of healthy men. Diabetes Metab. 2008 Feb;34(1):82-5. doi: 10.1016/j.diabet.2007.08.004. Epub 2007 Dec 11.
• [20] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [21] Arsenite and cadmium promote the development of mammary tumors. Carcinogenesis. 2020 Jul 14;41(7):1005-1014. doi: 10.1093/carcin/bgz176.
• [22] Effect of retinoic acid on gene expression in human conjunctival epithelium: secretory phospholipase A2 mediates retinoic acid induction of MUC16. Invest Ophthalmol Vis Sci. 2005 Nov;46(11):4050-61.
• [23] 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.
• [24] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [25] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [26] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [27] Anti-oncogenic and pro-differentiation effects of clorgyline, a monoamine oxidase A inhibitor, on high grade prostate cancer cells. BMC Med Genomics. 2009 Aug 20;2:55. doi: 10.1186/1755-8794-2-55.
• [28] 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.
• [29] PPARgamma controls CD1d expression by turning on retinoic acid synthesis in developing human dendritic cells. J Exp Med. 2006 Oct 2;203(10):2351-62.
• [30] Regulation of Hepatic Cholesteryl Ester Transfer Protein Expression and Reverse Cholesterol Transport by Inhibition of DNA Topoisomerase II. J Biol Chem. 2015 Jun 5;290(23):14418-29. doi: 10.1074/jbc.M115.643015. Epub 2015 Apr 25.
• [31] Adaptive homeostasis of the vitamin D-vitamin D nuclear receptor axis in 8-methoxypsoralen-induced hepatotoxicity. Toxicol Appl Pharmacol. 2019 Jan 1;362:150-158. doi: 10.1016/j.taap.2018.11.002. Epub 2018 Nov 10.
• [32] A toxicogenomic approach to drug-induced phospholipidosis: analysis of its induction mechanism and establishment of a novel in vitro screening system. Toxicol Sci. 2005 Feb;83(2):282-92.
• [33] Time series analysis of oxidative stress response patterns in HepG2: a toxicogenomics approach. Toxicology. 2013 Apr 5;306:24-34.
• [34] Determination of phospholipidosis potential based on gene expression analysis in HepG2 cells. Toxicol Sci. 2007 Mar;96(1):101-14.
• [35] Farnesoid X receptor induces murine scavenger receptor Class B type I via intron binding. PLoS One. 2012;7(4):e35895. doi: 10.1371/journal.pone.0035895. Epub 2012 Apr 23.
• [36] 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.
• [37] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [38] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [39] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [40] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [41] 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.
• [42] Primary Human Hepatocyte Spheroids as Tools to Study the Hepatotoxic Potential of Non-Pharmaceutical Chemicals. Int J Mol Sci. 2021 Oct 12;22(20):11005. doi: 10.3390/ijms222011005.
• [43] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.