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

General Information of Drug (ID: DMCLHZ5)

• Drug Name: splitomicin Drug Info
• Synonyms: splitomicin; 5690-03-9; 1,2-Dihydro-3H-naphtho[2,1-b]pyran-3-one; 1,2-dihydro-3h-benzo[f]chromen-3-one; 1H-benzo[f]chromen-3(2H)-one; CHEMBL86537; CHEBI:75272; 1,2-dihydrobenzo[f]chromen-3-one; 1H,2H,3H-naphtho[2,1-b]pyran-3-one; Splitomycin; Bio2_000878; Tocris-1542; AC1L1JZ6; AC1Q6ML4; KBioGR_000456; BSPBio_001116; KBioSS_000456; GTPL8101; SCHEMBL2544804; ZINC27374; KBio3_000852; KBio2_003024; BDBM29590; KBio3_000851; KBio2_005592; KBio2_000456; MolPort-003-959-546; ISFPDBUKMJDAJH-UHFFFAOYSA-N; HMS1362H17; HMS1990H17; Bio2_000398

Indication

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

• Cross-matching ID:
  PubChem CID: 5269
  ChEBI ID: CHEBI:75272
  CAS Number: CAS 5690-03-9
  TTD Drug ID: DMCLHZ5

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	[4]
GSK2245840	DMG7YQL	Chronic obstructive pulmonary disease	CA22	Phase 2	[5]
SEN-196	DMLDBQ5	Huntington disease	8A01.10	Phase 2	[6]
MB-12066	DMRSN2C	Obesity	5B81	Phase 2	[7]
SRT2379	DM7DAKX	Type-2 diabetes	5A11	Phase 1	[8]
SRT3025	DMRAXFH	Type-2 diabetes	5A11	Phase 1	[9]
PMID25435179-Compound-WO2012106509Salermide	DMLAH39	N. A.	N. A.	Patented	[4]
CAMBINOL	DMW46GY	Discovery agent	N.A.	Patented	[10]
PMID25435179-Compound-WO2012106509CAY10602	DM2F1T0	N. A.	N. A.	Patented	[4]
PMID25435179-Compound-WO2012106509Tenovin-6	DMBSOED	N. A.	N. A.	Patented	[4]

Drug(s) Affected By Serotransferrin (TF)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Ethanol	DMDRQZU	Chronic pain	MG30	Approved	[11]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[12]
Chlorpromazine	DMBGZI3	Acute intermittent hepatic porphyria	5C58.11	Approved	[13]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[14]
Isoflurophate	DMBSK7X	Glaucoma/ocular hypertension	9C61	Approved	[15]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[16]
Rosiglitazone	DMILWZR	Chronic kidney disease	GB61	Approved	[17]
Amiodarone	DMUTEX3	Tachyarrhythmias	BC71	Approved	[18]
Cupric Sulfate	DMP0NFQ	Fungal infection	1F29-1F2F	Approved	[19]
Clofibrate	DMPC1J7	Dysbetalipoproteinemia	5C80.2	Approved	[20]

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	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Serotransferrin (TF)	OT41PEMS	TRFE_HUMAN	Gene/Protein Processing	[3]

References

• [1] Identification of a small molecule inhibitor of Sir2p. Proc Natl Acad Sci U S A. 2001 Dec 18;98(26):15113-8.
• [2] Characterization of sirtuin inhibitors in nematodes expressing a muscular dystrophy protein reveals muscle cell and behavioral protection by specif... J Med Chem. 2010 Feb 11;53(3):1407-11.
• [3] Sirt1 inhibition promotes in vivo arterial thrombosis and tissue factor expression in stimulated cells. Cardiovasc Res. 2011 Feb 1;89(2):464-72. doi: 10.1093/cvr/cvq339. Epub 2010 Oct 26.
• [4] Sirtuin modulators: an updated patent review (2012 - 2014).Expert Opin Ther Pat. 2015 Jan;25(1):5-15.
• [5] Sirtuin 1 activator SRT2104 protects Huntington's disease mice. Ann Clin Transl Neurol. 2014 Dec;1(12):1047-52.
• [6] Sirtuin 1 (SIRT1): the misunderstood HDAC. J Biomol Screen. 2011 Dec;16(10):1153-69.
• [7] Pharmacological activation of Sirt1 ameliorates polyglutamine-induced toxicity through the regulation of autophagy.PLoS One.2013 Jun 10;8(6):e64953.
• [8] SRT2379, a small-molecule SIRT1 activator, fails to reduce cytokine release in a human endotoxemia model. Critical Care 2013, 17(Suppl 4):P8.
• [9] 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.
• [10] Novel cambinol analogs as sirtuin inhibitors: synthesis, biological evaluation, and rationalization of activity. J Med Chem. 2009 May 14;52(9):2673-82.
• [11] Cardiac toxicity from ethanol exposure in human-induced pluripotent stem cell-derived cardiomyocytes. Toxicol Sci. 2019 May 1;169(1):280-292.
• [12] 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.
• [13] Copper-stimulated endocytosis and degradation of the human copper transporter, hCtr1. J Biol Chem. 2003 Mar 14;278(11):9639-46. doi: 10.1074/jbc.M209455200. Epub 2002 Dec 25.
• [14] 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.
• [15] Tyrosines of human and mouse transferrin covalently labeled by organophosphorus agents: a new motif for binding to proteins that have no active site serine. Toxicol Sci. 2009 Jan;107(1):144-55. doi: 10.1093/toxsci/kfn211. Epub 2008 Oct 16.
• [16] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [17] Proteomic analysis of human adipose tissue after rosiglitazone treatment shows coordinated changes to promote glucose uptake. Obesity (Silver Spring). 2010 Jan;18(1):27-34. doi: 10.1038/oby.2009.208. Epub 2009 Jun 25.
• [18] Capturing time-dependent activation of genes and stress-response pathways using transcriptomics in iPSC-derived renal proximal tubule cells. Cell Biol Toxicol. 2023 Aug;39(4):1773-1793. doi: 10.1007/s10565-022-09783-5. Epub 2022 Dec 31.
• [19] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [20] Effect of clofibrate on plasma proteins including components of the hemostatic mechanism. Clin Chim Acta. 1976 Jan 2;66(1):9-17. doi: 10.1016/0009-8981(76)90366-1.