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

General Information of Drug (ID: DM5JWV9)

• Drug Name: Tiazofurin Drug Info
• Synonyms: Riboxamide; TCAR; TIZ; Tiazofurina; Tiazofurine; Tiazofurinum; Tiazole; Tiazofurin [USAN]; Tiazofurina [Spanish]; Tiazofurinum [Latin]; Cpd-5825; Tiazofurin (USAN); Tiazofurine (INN); 2-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-1,3-thiazole-4-carboxamide; 2-beta-D-Ribofuranosyl-4-thiazolecarboxamide; 2-ribofuranosylthiazole-4-carboxamide

Indication

Disease Entry	ICD 11	Status	REF
Solid tumour/cancer	2A00-2F9Z	Approved	[1]

• Therapeutic Class: Anticancer Agents
• Cross-matching ID:
  PubChem CID: 457954
  ChEBI ID: CHEMBL90239
  CAS Number: CAS 60084-10-8
  TTD Drug ID: DM5JWV9
  INTEDE Drug ID: DR2129

Molecule-Related Drug Atlas

Drug(s) Targeting Inosine-5'-monophosphate dehydrogenase 1 (IMPDH1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Mercaptopurine	DMTM2IK	Acute lymphoblastic leukaemia	2A85	Approved	[5]
Ribavirin	DMEYLH9	Hepatitis C virus infection	1E51.1	Approved	[6]
Merimepodib	DM0HS92	Breast cancer	2C60-2C65	Approved	[7]
Mizoribine	DMW6F0S	Transplant rejection	NE84	Approved	[7]
Viramidine	DMJFNR9	Hepatitis C virus infection	1E51.1	Phase 3	[8]
VX-944	DME321B	Solid tumour/cancer	2A00-2F9Z	Phase 2	[9]
VX-148	DML32R8	Psoriasis vulgaris	EA90	Patented	[10]
PMID28074661-Compound-US20100022547C81	DMM9E1U	N. A.	N. A.	Patented	[9]
PMID28074661-Compound-US20120264760C80	DM75QVW	N. A.	N. A.	Patented	[9]
Carbamide derivative 9	DMY06VC	N. A.	N. A.	Patented	[9]

Drug(s) Metabolized By Nicotinamide riboside kinase 2 (NRK2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Uridine	DMQTREB	Depression	6A70-6A7Z	Approved	[3]
cytidine	DMK0W8E	Discovery agent	N.A.	Investigative	[3]
D-ribosylnicotinate	DMYOLEV	N. A.	N. A.	Investigative	[3]

Drug(s) Metabolized By Nicotinamide riboside kinase 1 (NRK1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Uridine	DMQTREB	Depression	6A70-6A7Z	Approved	[3]
cytidine	DMK0W8E	Discovery agent	N.A.	Investigative	[3]
D-ribosylnicotinate	DMYOLEV	N. A.	N. A.	Investigative	[3]

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	[11]
Sertraline	DM0FB1J	Coronary heart disease	BA80.Z	Approved	[12]
Fulvestrant	DM0YZC6	Breast cancer	2C60-2C65	Approved	[13]
Gefitinib	DM15F0X	Colon adenocarcinoma		Approved	[14]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[15]
Selenium	DM25CGV	N. A.	N. A.	Approved	[16]
Ribavirin	DMEYLH9	Hepatitis C virus infection	1E51.1	Approved	[17]
Trametinib	DM2JGQ3	Melanoma	2C30	Approved	[18]
Sulindac	DM2QHZU	Acute myelogenous leukaemia	2A41	Approved	[19]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[20]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Inosine-5'-monophosphate dehydrogenase 1 (IMPDH1)	TTL7C8Q	IMDH1_HUMAN	Inhibitor	[2]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Nicotinamide riboside kinase 1 (NRK1)	DENV24I	NRK1_HUMAN	Substrate	[3]
Nicotinamide riboside kinase 2 (NRK2)	DE8DJ3N	NRK2_HUMAN	Substrate	[3]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Myc proto-oncogene protein (MYC)	OTPV5LUK	MYC_HUMAN	Gene/Protein Processing	[4]

References

• [1] De novo synthesis of two new cytotoxic tiazofurin analogues with modified sugar moieties. Bioorg Med Chem Lett. 2003 Oct 6;13(19):3167-70.
• [2] In vitro and in vivo antiproliferative activity of IPCAR, a new pyrazole nucleoside analog. Anticancer Res. 1998 Jul-Aug;18(4A):2623-30.
• [3] Nicotinamide riboside kinase structures reveal new pathways to NAD+. PLoS Biol. 2007 Oct 2;5(10):e263.
• [4] Regulation of the signal transduction program by drugs. Adv Enzyme Regul. 1997;37:35-55. doi: 10.1016/s0065-2571(96)00025-8.
• [5] Clinical pharmacology and pharmacogenetics of thiopurines. Eur J Clin Pharmacol. 2008 Aug;64(8):753-67.
• [6] Treating HCV with ribavirin analogues and ribavirin-like molecules. J Antimicrob Chemother. 2006 Jan;57(1):8-13.
• [7] VX-497: a novel, selective IMPDH inhibitor and immunosuppressive agent. J Pharm Sci. 2001 May;90(5):625-37.
• [8] Antiviral agents active against influenza A viruses. Nat Rev Drug Discov. 2006 Dec;5(12):1015-25.
• [9] Inosine-5'-monophosphate dehydrogenase (IMPDH) inhibitors: a patent and scientific literature review (2002-2016).Expert Opin Ther Pat. 2017 Jun;27(6):677-690.
• [10] Characterization of pharmacological efficacy of VX-148, a new, potent immunosuppressive inosine 5'-monophosphate dehydrogenase inhibitor. J Pharmacol Exp Ther. 2002 Sep;302(3):1272-7.
• [11] 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.
• [12] 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.
• [13] 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.
• [14] 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.
• [15] Arsenic suppresses gene expression in promyelocytic leukemia cells partly through Sp1 oxidation. Blood. 2005 Jul 1;106(1):304-10.
• [16] Selenite and selenomethionine promote HL-60 cell cycle progression. J Nutr. 2002 Apr;132(4):674-9. doi: 10.1093/jn/132.4.674.
• [17] 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.
• [18] 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.
• [19] Novel detection and differential utilization of a c-myc transcriptional block in colon cancer chemoprevention. Cancer Res. 2002 Nov 1;62(21):6006-10.
• [20] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.