Details of the Drug Combination

General Information of Drug Combination (ID: DCYD5O8)

• Drug Combination Name: Cerivastatin + Nitrosoglutathione
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Cerivastatin (DMXCM7H): Small molecular drug
  Nitrosoglutathione (DMZ9WI4): N.A.
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 0.95
  Bliss Independence Score: 0.95
  Loewe Additivity Score: 1.3
  LHighest Single Agent (HSA) Score: 1.31

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Cerivastatin

Disease Entry	ICD 11	Status	REF
Hyperlipidaemia	5C80	Approved	[2]
Multiple myeloma	2A83	Phase 1/2	[3]

Cerivastatin Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
HMG-CoA reductase (HMGCR)	TTPADOQ	HMDH_HUMAN	Inhibitor	[3]

Cerivastatin Interacts with 7 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Multidrug resistance-associated protein 2 (ABCC2)	DTFI42L	MRP2_HUMAN	Substrate	[4]
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[4]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[5]
Organic anion transporting polypeptide 1B1 (SLCO1B1)	DT3D8F0	SO1B1_HUMAN	Substrate	[6]
Sodium/taurocholate cotransporting polypeptide (SLC10A1)	DT56EKP	NTCP_HUMAN	Substrate	[7]
Organic anion transporting polypeptide 1B3 (SLCO1B3)	DT9C1TS	SO1B3_HUMAN	Substrate	[6]
Organic anion transporting polypeptide 2B1 (SLCO2B1)	DTPFTEQ	SO2B1_HUMAN	Substrate	[8]

Cerivastatin Interacts with 6 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[9]
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DEYGVN4	UD11_HUMAN	Metabolism	[10]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[11]
Cytochrome P450 3A7 (CYP3A7)	DERD86B	CP3A7_HUMAN	Metabolism	[11]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Metabolism	[12]
UDP-glucuronosyltransferase 1A3 (UGT1A3)	DEF2WXN	UD13_HUMAN	Metabolism	[10]

Cerivastatin Interacts with 1 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Ryanodine receptor 2 (RYR2)	OT0PF19E	RYR2_HUMAN	Increases ADR	[13]

Nitrosoglutathione Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
S-(hydroxymethyl)glutathione dehydrogenase (adh)	DEAH3PE	A0A0A7DS01_VIBCL	Metabolism	[14]

Nitrosoglutathione Interacts with 19 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Serine protease HTRA2, mitochondrial (HTRA2)	OTC7616F	HTRA2_HUMAN	Affects Localization	[15]
Tumor necrosis factor (TNF)	OT4IE164	TNFA_HUMAN	Increases Secretion	[16]
Interferon gamma (IFNG)	OTXG9JM7	IFNG_HUMAN	Increases Secretion	[16]
C-X-C motif chemokine 10 (CXCL10)	OTTLQ6S0	CXL10_HUMAN	Decreases Secretion	[16]
Interleukin-5 (IL5)	OTAFPSCO	IL5_HUMAN	Decreases Secretion	[16]
Transcription factor Sp1 (SP1)	OTISPT4X	SP1_HUMAN	Increases Activity	[17]
Heme oxygenase 1 (HMOX1)	OTC1W6UX	HMOX1_HUMAN	Increases Expression	[18]
C-C motif chemokine 5 (CCL5)	OTSCA5CK	CCL5_HUMAN	Decreases Secretion	[16]
Cystic fibrosis transmembrane conductance regulator (CFTR)	OT6B22QH	CFTR_HUMAN	Decreases Expression	[17]
Interleukin-10 (IL10)	OTIRFRXC	IL10_HUMAN	Decreases Secretion	[16]
Interleukin-12 subunit beta (IL12B)	OT0JF8A3	IL12B_HUMAN	Decreases Expression	[16]
T-lymphocyte activation antigen CD86 (CD86)	OTJCSBPC	CD86_HUMAN	Decreases Expression	[16]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[15]
Transcription factor Sp3 (SP3)	OTYDQZ1T	SP3_HUMAN	Decreases Activity	[17]
Caspase-8 (CASP8)	OTA8TVI8	CASP8_HUMAN	Increases Activity	[15]
Hypoxia-inducible factor 1-alpha (HIF1A)	OTADSC03	HIF1A_HUMAN	Increases Expression	[19]
Carbonyl reductase 1 (CBR1)	OTQ3A541	CBR1_HUMAN	Increases Reduction	[20]
Serine-protein kinase ATM (ATM)	OTQVOHLT	ATM_HUMAN	Increases Response To Substance	[21]
Alcohol dehydrogenase class-3 (ADH5)	OTSO67MI	ADHX_HUMAN	Increases Reduction	[22]

References

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• [5] Mammalian drug efflux transporters of the ATP binding cassette (ABC) family in multidrug resistance: A review of the past decade. Cancer Lett. 2016 Jan 1;370(1):153-64.
• [6] FDA Drug Development and Drug Interactions
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• [8] pH-sensitive interaction of HMG-CoA reductase inhibitors (statins) with organic anion transporting polypeptide 2B1. Mol Pharm. 2011 Aug 1;8(4):1303-13.
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• [11] Drug Interactions Flockhart Table
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• [14] Nitrosative stress response in Vibrio cholerae: role of S-nitrosoglutathione reductase. Appl Biochem Biotechnol. 2017 Jul;182(3):871-884.
• [15] The induction of reactive oxygen species and loss of mitochondrial Omi/HtrA2 is associated with S-nitrosoglutathione-induced apoptosis in human endothelial cells. Toxicol Appl Pharmacol. 2010 May 1;244(3):374-84. doi: 10.1016/j.taap.2010.02.004. Epub 2010 Feb 11.
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• [17] Concentration-dependent effects of endogenous S-nitrosoglutathione on gene regulation by specificity proteins Sp3 and Sp1. Biochem J. 2004 May 15;380(Pt 1):67-74. doi: 10.1042/BJ20031687.
• [18] Induction of heme oxygenase-1 as a response in sensing the signals evoked by distinct nitric oxide donors. Biochem Pharmacol. 1999 Jul 15;58(2):227-36. doi: 10.1016/s0006-2952(99)00097-0.
• [19] Regulation of the hypoxia-inducible factor 1alpha by the inflammatory mediators nitric oxide and tumor necrosis factor-alpha in contrast to desferroxamine and phenylarsine oxide. J Biol Chem. 2001 Oct 26;276(43):39805-11. doi: 10.1074/jbc.M107689200. Epub 2001 Aug 20.
• [20] Studies on reduction of S-nitrosoglutathione by human carbonyl reductases 1 and 3. Chem Biol Interact. 2011 May 30;191(1-3):95-103.
• [21] Hypersensitivity of ataxia-telangiectasia fibroblasts to a nitric oxide donor. Free Radic Biol Med. 1997;22(1-2):343-7. doi: 10.1016/s0891-5849(96)00336-x.
• [22] The Janus face of alcohol dehydrogenase 3. Chem Biol Interact. 2009 Mar 16;178(1-3):29-35. doi: 10.1016/j.cbi.2008.10.050. Epub 2008 Nov 6.