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

General Information of Drug (ID: DMW46GY)

• Drug Name: CAMBINOL Drug Info
• Synonyms: cambinol; 14513-15-6; SIRT1/2 Inhibitor IV, Cambinol; NSC112546; NSC-112546; NSC-1125476; 5-[(2-hydroxy-1-naphthyl)methyl]-2-mercapto-6-phenyl-4(3H)-Pyrimidinone; 5-(2-Hydroxynaphthalen-1-ylmethyl)-6-phenyl-2-thioxo-2,3-dihydro-1H-pyrimidin-4-one; 5-(2-Hydroxy-naphthalen-1-ylmethyl)-6-phenyl-2-thioxo-2,3-dihydro-1H-pyrimidin-4-one; Tetrahydro-5-[(2-hydroxy-1-naphthalenyl)methyl]-6-phenyl-2-thioxo-4(1H)-Pyrimidinone; AC1MMYEF; NCIStruc2_001159; NCIStruc1_001428; SCHEMBL2538372; CHEMBL491960; CTK8G3107; BDBM29040

Indication

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

• Cross-matching ID:
  PubChem CID: 3246390
  CAS Number: CAS 14513-15-6
  TTD Drug ID: DMW46GY

Molecule-Related Drug Atlas

Drug(s) Targeting NAD-dependent deacetylase sirtuin-1 (SIRT1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Resveratrol	DM3RWXL	Giant cell arteritis	4A44.2	Phase 3	[3]
GSK2245840	DMG7YQL	Chronic obstructive pulmonary disease	CA22	Phase 2	[4]
SEN-196	DMLDBQ5	Huntington disease	8A01.10	Phase 2	[5]
MB-12066	DMRSN2C	Obesity	5B81	Phase 2	[6]
SRT2379	DM7DAKX	Type-2 diabetes	5A11	Phase 1	[7]
SRT3025	DMRAXFH	Type-2 diabetes	5A11	Phase 1	[8]
PMID25435179-Compound-WO2012106509Salermide	DMLAH39	N. A.	N. A.	Patented	[3]
PMID25435179-Compound-WO2012106509CAY10602	DM2F1T0	N. A.	N. A.	Patented	[3]
PMID25435179-Compound-WO2012106509Tenovin-6	DMBSOED	N. A.	N. A.	Patented	[3]
GSK184072	DMMIR1K	Colon cancer	2B90.Z	Discontinued in Phase 2	[9]

Drug(s) Affected By ATP-binding cassette sub-family C member 3 (ABCC3)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Paclitaxel	DMLB81S	Breast carcinoma		Approved	[10]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[11]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[12]
Calcipotriol	DM03CP7	Psoriasis	EA90	Approved	[13]
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[14]
Fulvestrant	DM0YZC6	Breast cancer	2C60-2C65	Approved	[15]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[16]
Prednisone	DM2HG4X	Acute asthma	CA23	Approved	[17]
Sulindac	DM2QHZU	Acute myelogenous leukaemia	2A41	Approved	[18]
Simvastatin	DM30SGU	Arteriosclerosis	BD40	Approved	[19]

Drug(s) Affected By ATP-dependent translocase ABCB1 (ABCB1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Flupentixol	DM0DJ9O	Schizophrenia	6A20	Approved	[20]
Sertraline	DM0FB1J	Coronary heart disease	BA80.Z	Approved	[21]
Crizotinib	DM4F29C	Non-small-cell lung cancer	2C25.Y	Approved	[22]
Lamotrigine	DM8SXYG	Bipolar disorder	6A60	Approved	[23]
Cepharanthine	DM9Y5JB	N. A.	N. A.	Approved	[24]
Itraconazole	DMCR1MV	Aspergillosis	1F20	Approved	[25]
Clozapine	DMFC71L	Schizophrenia	6A20	Approved	[26]
Midostaurin	DMI6E0R	Acute myeloid leukaemia	2A60	Approved	[27]
Trifluoperazine	DMKBYWI	Anxiety		Approved	[28]
Olanzapine	DMPFN6Y	Bipolar depression		Approved	[26]

Drug(s) Affected By NAD-dependent protein deacetylase sirtuin-2 (SIRT2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[29]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[30]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[31]
Ethanol	DMDRQZU	Chronic pain	MG30	Approved	[32]
Clozapine	DMFC71L	Schizophrenia	6A20	Approved	[33]
Paclitaxel	DMLB81S	Breast carcinoma		Approved	[34]
Vitamin B3	DMQVRZH	Chronic renal failure	GB61.Z	Approved	[35]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[36]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[37]
Nicotinamide	DMUPE07	Acne vulgaris	ED80	Approved	[38]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
NAD-dependent deacetylase sirtuin-1 (SIRT1)	TTUF2HO	SIR1_HUMAN	Inhibitor	[1]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
ATP-binding cassette sub-family C member 3 (ABCC3)	OTC3IJV4	MRP3_HUMAN	Gene/Protein Processing	[2]
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Gene/Protein Processing	[2]
NAD-dependent protein deacetylase sirtuin-2 (SIRT2)	OT5Q6SVK	SIR2_HUMAN	Gene/Protein Processing	[2]

References

• [1] Novel cambinol analogs as sirtuin inhibitors: synthesis, biological evaluation, and rationalization of activity. J Med Chem. 2009 May 14;52(9):2673-82.
• [2] Inhibition of sirtuins 1 and 2 impairs cell survival and migration and modulates the expression of P-glycoprotein and MRP3 in hepatocellular carcinoma cell lines. Toxicol Lett. 2018 Jun 1;289:63-74. doi: 10.1016/j.toxlet.2018.03.011. Epub 2018 Mar 12.
• [3] Sirtuin modulators: an updated patent review (2012 - 2014).Expert Opin Ther Pat. 2015 Jan;25(1):5-15.
• [4] Sirtuin 1 activator SRT2104 protects Huntington's disease mice. Ann Clin Transl Neurol. 2014 Dec;1(12):1047-52.
• [5] Sirtuin 1 (SIRT1): the misunderstood HDAC. J Biomol Screen. 2011 Dec;16(10):1153-69.
• [6] Pharmacological activation of Sirt1 ameliorates polyglutamine-induced toxicity through the regulation of autophagy.PLoS One.2013 Jun 10;8(6):e64953.
• [7] SRT2379, a small-molecule SIRT1 activator, fails to reduce cytokine release in a human endotoxemia model. Critical Care 2013, 17(Suppl 4):P8.
• [8] The Sirt1 Activators SRT2183 and SRT3025 Inhibit RANKL-Induced Osteoclastogenesis in Bone Marrow-Derived Macrophages and Down-Regulate Sirt3 in Sirt1 Null Cells. PLoS One. 2015 Jul 30;10(7):e0134391.
• [9] Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
• [10] Evaluation of drug transporters' significance for multidrug resistance in head and neck squamous cell carcinoma. Head Neck. 2011 Jul;33(7):959-68. doi: 10.1002/hed.21559. Epub 2010 Aug 24.
• [11] Gene expression profiling of leukemia T-cells resistant to methotrexate and 7-hydroxymethotrexate reveals alterations that preserve intracellular levels of folate and nucleotide biosynthesis. Biochem Pharmacol. 2009 Apr 15;77(8):1410-7.
• [12] Drug sensitivity and drug resistance profiles of human intrahepatic cholangiocarcinoma cell lines. World J Gastroenterol. 2005 May 14;11(18):2748-53. doi: 10.3748/wjg.v11.i18.2748.
• [13] 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.
• [14] Cannabidiol induces antioxidant pathways in keratinocytes by targeting BACH1. Redox Biol. 2020 Jan;28:101321. doi: 10.1016/j.redox.2019.101321. Epub 2019 Sep 5.
• [15] 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.
• [16] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [17] Differential regulation of the human MRP2 and MRP3 gene expression by glucocorticoids. J Steroid Biochem Mol Biol. 2005 Aug;96(3-4):229-34. doi: 10.1016/j.jsbmb.2005.03.004.
• [18] Induction of multidrug resistance proteins MRP1 and MRP3 and gamma-glutamylcysteine synthetase gene expression by nonsteroidal anti-inflammatory drugs in human colon cancer cells. Biochem Biophys Res Commun. 2002 Feb 8;290(5):1427-33. doi: 10.1006/bbrc.2002.6367.
• [19] Activation of nuclear factor-kappa B pathway by simvastatin and RhoA silencing increases doxorubicin cytotoxicity in human colon cancer HT29 cells. Mol Pharmacol. 2008 Aug;74(2):476-84.
• [20] Characteristics of P388/VMDRC.04, a simple, sensitive model for studying P-glycoprotein antagonists. Cancer Res. 1994 Feb 1;54(3):730-7.
• [21] Michaelis-Menten kinetic analysis of drugs of abuse to estimate their affinity to human P-glycoprotein. Toxicol Lett. 2013 Feb 27;217(2):137-42. doi: 10.1016/j.toxlet.2012.12.012. Epub 2012 Dec 27.
• [22] Editor's Highlight: PlacentalDisposition and Effects of Crizotinib: An Ex Vivo Study in the Isolated Dual-Side Perfused Human Cotyledon. Toxicol Sci. 2017 Jun 1;157(2):500-509. doi: 10.1093/toxsci/kfx063.
• [23] Functional evaluation of polymorphisms in the human ABCB1 gene and the impact on clinical responses of antiepileptic drugs. Pharmacogenet Genomics. 2008 May;18(5):390-402. doi: 10.1097/FPC.0b013e3282f85e36.
• [24] Cepharanthine potently enhances the sensitivity of anticancer agents in K562 cells. Cancer Sci. 2005 Jun;96(6):372-6. doi: 10.1111/j.1349-7006.2005.00057.x.
• [25] Clinical pharmacokinetic monitoring of itraconazole is warranted in only a subset of patients. Ther Drug Monit. 2005 Jun;27(3):322-33. doi: 10.1097/01.ftd.0000150135.22645.ea.
• [26] Evaluation of antipsychotic drugs as inhibitors of multidrug resistance transporter P-glycoprotein. Psychopharmacology (Berl). 2006 Sep;187(4):415-23. doi: 10.1007/s00213-006-0437-9. Epub 2006 Jun 30.
• [27] Actions of the selective protein kinase C inhibitor PKC412 on B-chronic lymphocytic leukemia cells in vitro. Haematologica. 2002 Feb;87(2):167-76.
• [28] Characterization of the ATPase activity of the Mr 170,000 to 180,000 membrane glycoprotein (P-glycoprotein) associated with multidrug resistance in K562/ADM cells. Cancer Res. 1988 Sep 1;48(17):4926-32.
• [29] 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.
• [30] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
• [31] 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.
• [32] Pterostilbene attenuates RIPK3-dependent hepatocyte necroptosis in alcoholic liver disease via SIRT2-mediated NFATc4 deacetylation. Toxicology. 2021 Sep;461:152923. doi: 10.1016/j.tox.2021.152923. Epub 2021 Aug 30.
• [33] Toxicoproteomics reveals an effect of clozapine on autophagy in human liver spheroids. Toxicol Mech Methods. 2023 Jun;33(5):401-410. doi: 10.1080/15376516.2022.2156005. Epub 2022 Dec 19.
• [34] Norcantharidin combined with paclitaxel induces endoplasmic reticulum stress mediated apoptotic effect in prostate cancer cells by targeting SIRT7 expression. Environ Toxicol. 2021 Nov;36(11):2206-2216. doi: 10.1002/tox.23334. Epub 2021 Jul 16.
• [35] Effects of niacin restriction on sirtuin and PARP responses to photodamage in human skin. PLoS One. 2012;7(7):e42276. doi: 10.1371/journal.pone.0042276. Epub 2012 Jul 31.
• [36] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [37] Genome-Wide Analysis of Low Dose Bisphenol-A (BPA) Exposure in Human Prostate Cells. Curr Genomics. 2019 May;20(4):260-274. doi: 10.2174/1389202920666190603123040.
• [38] Effects of histone deacetylase inhibitors, sodium phenyl butyrate and vitamin B3, in combination with retinoic acid on granulocytic differentiation of human promyelocytic leukemia HL-60 cells. Ann N Y Acad Sci. 2006 Dec;1091:356-67. doi: 10.1196/annals.1378.080.