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

General Information of Drug (ID: DMG6KXB)

• Drug Name: MK-8245 Drug Info
• Synonyms: MK-8245; 1030612-90-8; MK8245; MK 8245; UNII-537E7QE8LX; 537E7QE8LX; CHEMBL1938870; 5-[3-[4-(2-Bromo-5-fluorophenoxy)-1-piperidinyl]-5-isoxazolyl]-2H-tetrazole-2-acetic acid; 2H-Tetrazole-2-acetic acid, 5-[3-[4-(2-bromo-5-fluorophenoxy)-1-piperidinyl]-5-isoxazolyl]-;2H-Tetrazole-2-acetic acid, 5-[3-[4-(2-bromo-5-fluorophenoxy)-1-piperidinyl]-5-isoxazolyl]-; 2-(5-(3-(4-(2-bromo-5-fluorophenoxy)piperidin-1-yl)isoxazol-5-yl)-2H-tetrazol-2-yl)acetic acid; UJEAABFSXKCSGI-UHFFFAOYSA-N; C17H16BrFN6O4; MLS006011144

Indication

Disease Entry	ICD 11	Status	REF
Type-2 diabetes	5A11	Phase 2	[1]

• Cross-matching ID:
  PubChem CID: 24988881
  CAS Number: CAS 1030612-90-8
  TTD Drug ID: DMG6KXB

Molecule-Related Drug Atlas

Drug(s) Targeting Acyl-CoA desaturase (SCD)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Isoxyl	DMJL10P	Bacterial infection	1A00-1C4Z	Approved	[3]
Aramchol	DMDLGRO	Lipid metabolism disorder	5C52.Z	Phase 2/3	[4]
Sterculic acid	DM1PMR3	Discovery agent	N.A.	Investigative	[5]
ISIS 147919	DMTE3FJ	Discovery agent	N.A.	Investigative	[6]
2-(4-benzoylpiperazin-1-yl)thiazole-5-carboxamide	DMJA5Y4	Discovery agent	N.A.	Investigative	[7]
MF-152	DMBLUSA	Discovery agent	N.A.	Investigative	[8]
CVT-12012	DMOCKMZ	Diabetic complication	5A2Y	Investigative	[9]

Drug(s) Affected By Solute carrier organic anion transporter family member 1B1 (SLCO1B1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Enalapril	DMNFUZR	Congestive heart failure	BD10	Approved	[10]
Lovastatin	DM9OZWQ	Arteriosclerosis	BD40	Approved	[11]
Bosentan	DMIOGBU	Pulmonary arterial hypertension	BB01.0	Approved	[12]
Repaglinide	DM5SXUV	Diabetic complication	5A2Y	Approved	[13]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[14]
Simvastatin	DM30SGU	Arteriosclerosis	BD40	Approved	[15]
Cholic Acid	DM7OKQV	Cholelithiasis	DC11	Approved	[16]
Ursodeoxycholic acid	DMCUT21	Cholelithiasis	DC11	Approved	[16]
Hydroxyurea	DMOQVU9	Chronic myelogenous leukaemia	2A20.0	Approved	[17]
Irinotecan	DMP6SC2	Adenocarcinoma	2D40	Approved	[18]

Drug(s) Affected By Solute carrier organic anion transporter family member 1B3 (SLCO1B3)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Warfarin	DMJYCVW	Atrial fibrillation	BC81.3	Approved	[19]
Fexofenadine	DM17ONX	Allergic rhinitis	CA08.0	Approved	[20]
Hydroxyurea	DMOQVU9	Chronic myelogenous leukaemia	2A20.0	Approved	[17]
Trospium chloride	DM32XZT	Discovery agent	N.A.	Approved	[21]
Deoxycholic acid	DM3GYAL	Subcutaneous fat disorder	EF02	Approved	[22]
obeticholic acid	DM3Q1SM	Primary biliary cholangitis	DB96.1	Approved	[23]
Rifampicin	DM5DSFZ	Non-insulin dependent diabetes	5A11	Approved	[24]
Cholic Acid	DM7OKQV	Cholelithiasis	DC11	Approved	[22]
Calcitriol	DM8ZVJ7	Congenital alopecia	LC30	Approved	[25]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[26]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Acyl-CoA desaturase (SCD)	TT6RIOV	ACOD_HUMAN	Inhibitor	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Solute carrier organic anion transporter family member 1B1 (SLCO1B1)	OTNEN8QK	SO1B1_HUMAN	Regulation of Drug Effects	[2]
Solute carrier organic anion transporter family member 1B3 (SLCO1B3)	OTOM3BUH	SO1B3_HUMAN	Regulation of Drug Effects	[2]

References

• [1] ClinicalTrials.gov (NCT00846391) A Study to Assess the Safety and Efficacy of MK8245 in Patients With Type 2 Diabetes Mellitus and Inadequate Glycemic Control (MK8245-005 AM2). U.S. National Institutes of Health.
• [2] Development of a liver-targeted stearoyl-CoA desaturase (SCD) inhibitor (MK-8245) to establish a therapeutic window for the treatment of diabetes and dyslipidemia. J Med Chem. 2011 Jul 28;54(14):5082-96.
• [3] Has nature already identified all useful antibacterial targets Curr Opin Microbiol. 2008 Oct;11(5):387-92.
• [4] The fatty acid-bile acid conjugate Aramchol reduces liver fat content in patients with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol. 2014 Dec;12(12):2085-91.e1.
• [5] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [6] US patent application no. 7,132,529, Antisense modulation of stearoyl-CoA desaturase expression.
• [7] Thiazole analog as stearoyl-CoA desaturase 1 inhibitor. Bioorg Med Chem Lett. 2009 Sep 1;19(17):5214-7.
• [8] SAR and optimization of thiazole analogs as potent stearoyl-CoA desaturase inhibitors. Bioorg Med Chem Lett. 2010 Mar 1;20(5):1593-7.
• [9] Potent, orally bioavailable, liver-selective stearoyl-CoA desaturase (SCD) inhibitors. Bioorg Med Chem Lett. 2009 Aug 1;19(15):4070-4.
• [10] Effect of organic anion-transporting polypeptide 1B1 (OATP1B1) polymorphism on the single- and multiple-dose pharmacokinetics of enalapril in healthy Chinese adult men. Clin Ther. 2011 May;33(5):655-63. doi: 10.1016/j.clinthera.2011.04.018.
• [11] Differential interaction of 3-hydroxy-3-methylglutaryl-coa reductase inhibitors with ABCB1, ABCC2, and OATP1B1. Drug Metab Dispos. 2005 Apr;33(4):537-46.
• [12] Omics-based responses induced by bosentan in human hepatoma HepaRG cell cultures. Arch Toxicol. 2018 Jun;92(6):1939-1952.
• [13] Polymorphic organic anion transporting polypeptide 1B1 is a major determinant of repaglinide pharmacokinetics. Clin Pharmacol Ther. 2005 Jun;77(6):468-78. doi: 10.1016/j.clpt.2005.01.018.
• [14] SLC19A1, SLC46A1 and SLCO1B1 polymorphisms as predictors of methotrexate-related toxicity in Portuguese rheumatoid arthritis patients. Toxicol Sci. 2014 Nov;142(1):196-209. doi: 10.1093/toxsci/kfu162. Epub 2014 Aug 14.
• [15] SLCO1B1 variants and statin-induced myopathy--a genomewide study. N Engl J Med. 2008 Aug 21;359(8):789-99.
• [16] Transport of fluorescent chenodeoxycholic acid via the human organic anion transporters OATP1B1 and OATP1B3. J Lipid Res. 2006 Jun;47(6):1196-202.
• [17] Transcellular movement of hydroxyurea is mediated by specific solute carrier transporters. Exp Hematol. 2011 Apr;39(4):446-56.
• [18] Severe toxicities after irinotecan-based chemotherapy in a patient with lung cancer: a homozygote for the SLCO1B1*15 allele. Ther Drug Monit. 2007 Oct;29(5):666-8. doi: 10.1097/FTD.0b013e3181357364.
• [19] Identification of two novel genes SLC15A2 and SLCO1B3 associated with maintenance dose variability of warfarin in a Chinese population. Sci Rep. 2017 Dec 12;7(1):17379. doi: 10.1038/s41598-017-17731-1.
• [20] Involvement of multiple efflux transporters in hepatic disposition of fexofenadine. Mol Pharmacol. 2008 May;73(5):1474-83.
• [21] Expression of drug transporters and drug metabolizing enzymes in the bladder urothelium in man and affinity of the bladder spasmolytic trospium chloride to transporters likely involved in its pharmacokinetics. Mol Pharm. 2015 Jan 5;12(1):171-8.
• [22] Potency of individual bile acids to regulate bile acid synthesis and transport genes in primary human hepatocyte cultures. Toxicol Sci. 2014 Oct;141(2):538-46. doi: 10.1093/toxsci/kfu151. Epub 2014 Jul 23.
• [23] Pharmacotoxicology of clinically-relevant concentrations of obeticholic acid in an organotypic human hepatocyte system. Toxicol In Vitro. 2017 Mar;39:93-103.
• [24] Rifampin Regulation of Drug Transporters Gene Expression and the Association of MicroRNAs in Human Hepatocytes. Front Pharmacol. 2016 Apr 26;7:111.
• [25] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [26] 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.