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

General Information of Drug (ID: DMHY3IP)

• Drug Name: Lobeglitazone Drug Info
• Synonyms: Lobeglitazone sulfate; CKD-501; Dual PPARalpha/delta (type 2 diabetes), Chong Kun Dang

Indication

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

• Cross-matching ID:
  PubChem CID: 9826451
  ChEBI ID: CHEBI:136052
  CAS Number: CAS 607723-33-1
  TTD Drug ID: DMHY3IP
  INTEDE Drug ID: DR0966

Molecule-Related Drug Atlas

Drug(s) Metabolized By Cytochrome P450 3A4 (CYP3A4)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxorubicin	DMVP5YE	Solid tumour/cancer	2A00-2F9Z	Approved	[4]
Progesterone	DMUY35B	Premature labour	JB00	Approved	[5]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[6]
Estradiol	DMUNTE3	Breast cancer	2C60-2C65	Approved	[7]
Acetaminophen	DMUIE76	Pain	MG30-MG3Z	Approved	[8]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[9]
Etoposide	DMNH3PG	Solid tumour/cancer	2A00-2F9Z	Approved	[10]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[11]
Prasterone	DM67VKL	Chronic obstructive pulmonary disease	CA22	Approved	[5]
Verapamil	DMA7PEW	Hypertension	BA00-BA04	Approved	[12]

Drug(s) Metabolized By Cytochrome P450 2C8 (CYP2C8)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Fluorouracil	DMUM7HZ	Solid tumour/cancer	2A00-2F9Z	Approved	[13]
Estradiol	DMUNTE3	Breast cancer	2C60-2C65	Approved	[14]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[14]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[15]
Verapamil	DMA7PEW	Hypertension	BA00-BA04	Approved	[16]
Diclofenac	DMPIHLS	Osteoarthritis	FA00-FA05	Approved	[17]
Sorafenib	DMS8IFC	Hepatocellular carcinoma	2C12.02	Approved	[18]
Quinine	DMSWYF5	Malaria	1F40-1F45	Approved	[14]
Mycophenolate mofetil	DMPQAGE	Organ transplant rejection	NE84	Approved	[19]
Propofol	DMB4OLE	Anaesthesia	9A78.6	Approved	[20]

Drug(s) Targeting Peroxisome proliferator-activated receptor gamma (PPAR-gamma)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Troglitazone	DM3VFPD	Diabetic complication	5A2Y	Approved	[21]
Pioglitazone	DMKJ485	Diabetic complication	5A2Y	Approved	[22]
Rosiglitazone XR	DMT45MU	Type-2 diabetes	5A11	Approved	[23]
Thiazolidinedione	DMC1NBW	Alzheimer disease	8A20	Approved	[22]
Glitazone	DMDN4A1	N. A.	N. A.	Phase 4	[24]
Muraglitazar	DMG3NFZ	N. A.	N. A.	Phase 3	[25]
Rosiglitazone + metformin	DMPIDXT	Diabetic complication	5A2Y	Phase 3	[23]
Rivoglitazone	DMBY31K	Ocular inflammation	9C61.24	Phase 3	[26]
Balaglitazone	DMXBHR6	Type-1 diabetes	5A10	Phase 3	[27]
Ragaglitazar	DMFSHEM	Type-1 diabetes	5A10	Phase 3	[28]

Drug(s) Targeting Peroxisome proliferator-activated receptor alpha (PPARA)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Fenofibrate	DMFKXDY	High cholesterol level	5C80.0	Approved	[24]
Bezafibrate	DMZDCS0	Hyperlipidaemia	5C80	Approved	[29]
Ciprofibrate	DMGC5DB	Hyperlipoproteinemia	5C80	Approved	[24]
Pemafibrate	DMD1VZL	Hyperlipidemia	5C80.Z	Approved	[30]
Muraglitazar	DMG3NFZ	N. A.	N. A.	Phase 3	[25]
Ragaglitazar	DMFSHEM	Type-1 diabetes	5A10	Phase 3	[28]
CS-038	DM67P0F	Type-2 diabetes	5A11	Phase 3	[31]
TESAGLITAZAR	DMGRBN5	Type-1 diabetes	5A10	Phase 3	[32]
GFT-505	DM7ZOAE	Non-alcoholic steatohepatitis	DB92.1	Phase 3	[33]
ZYH-1	DMMBJYC	Lipid metabolism disorder	5C52.Z	Phase 3	[34]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Peroxisome proliferator-activated receptor alpha (PPARA)	TTJ584C	PPARA_HUMAN	Agonist	[1]
Peroxisome proliferator-activated receptor gamma (PPAR-gamma)	TTZMAO3	PPARG_HUMAN	Agonist	[1]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Substrate	[2]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Substrate	[3]

References

• [1] Tolerability and pharmacokinetics of lobeglitazone, a novel peroxisome proliferator-activated receptor-gamma agonist, after a single oral administration in healthy female subjects. Clin Drug Investig. 2014 Jul;34(7):467-74.
• [2] Lack of the effect of lobeglitazone, a peroxisome proliferator-activated receptor-gamma agonist, on the pharmacokinetics and pharmacodynamics of warfarin. Drug Des Devel Ther. 2015 Mar 2;9:737-43.
• [3] Effects of gemfibrozil, itraconazole, and their combination on the pharmacokinetics of pioglitazone. Clin Pharmacol Ther. 2005 May;77(5):404-14.
• [4] Expression levels and activation of a PXR variant are directly related to drug resistance in osteosarcoma cell lines. Cancer. 2007 Mar 1;109(5):957-65.
• [5] Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
• [6] Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. J Pharmacol Exp Ther. 2004 Sep;310(3):1062-75.
• [7] Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
• [8] Metabolic interactions between acetaminophen (paracetamol) and two flavonoids, luteolin and quercetin, through in-vitro inhibition studies. J Pharm Pharmacol. 2017 Dec;69(12):1762-1772.
• [9] Potent mechanism-based inhibition of CYP3A4 by imatinib explains its liability to interact with CYP3A4 substrates. Br J Pharmacol. 2012 Apr;165(8):2787-98.
• [10] Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
• [11] The metabolism of zidovudine by human liver microsomes in vitro: formation of 3'-amino-3'-deoxythymidine. Biochem Pharmacol. 1994 Jul 19;48(2):267-76.
• [12] Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
• [13] Roles of cytochromes P450 1A2, 2A6, and 2C8 in 5-fluorouracil formation from tegafur, an anticancer prodrug, in human liver microsomes. Drug Metab Dispos. 2000 Dec;28(12):1457-63.
• [14] Role of cytochrome P450 2C8 in drug metabolism and interactions. Pharmacol Rev. 2016 Jan;68(1):168-241.
• [15] Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
• [16] Differential expression and function of CYP2C isoforms in human intestine and liver. Pharmacogenetics. 2003 Sep;13(9):565-75.
• [17] Analysis of human cytochrome P450 2C8 substrate specificity using a substrate pharmacophore and site-directed mutants. Biochemistry. 2004 Dec 14;43(49):15379-92.
• [18] Interaction of sorafenib and cytochrome P450 isoenzymes in patients with advanced melanoma: a phase I/II pharmacokinetic interaction study. Cancer Chemother Pharmacol. 2011 Nov;68(5):1111-8.
• [19] PharmGKB summary: mycophenolic acid pathway. Pharmacogenet Genomics. 2014 Jan;24(1):73-9.
• [20] Possible involvement of multiple human cytochrome P450 isoforms in the liver metabolism of propofol. Br J Anaesth. 1998 Jun;80(6):788-95.
• [21] Expression of peroxisome proliferator-activated receptors (PPARs) in human urinary bladder carcinoma and growth inhibition by its agonists. Int J Cancer. 2003 May 1;104(5):597-602.
• [22] Functional PPAR-gamma receptor is a novel therapeutic target for ACTH-secreting pituitary adenomas. Nat Med. 2002 Nov;8(11):1281-7.
• [23] Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
• [24] Peroxisome proliferator-activated receptor alpha activators improve insulin sensitivity and reduce adiposity. J Biol Chem. 2000 Jun 2;275(22):16638-42.
• [25] Muraglitazar, a dual (alpha/gamma) PPAR activator: a randomized, double-blind, placebo-controlled, 24-week monotherapy trial in adult patients with... Clin Ther. 2005 Aug;27(8):1181-95.
• [26] A randomized-controlled trial to investigate the effects of rivoglitazone, a novel PPAR gamma agonist on glucose-lipid control in type 2 diabetes. Diabetes Obes Metab. 2011 Sep;13(9):806-13.
• [27] Balaglitazone: a second generation peroxisome proliferator-activated receptor (PPAR) gamma () agonist.Mini Rev Med Chem.2012 Feb;12(2):87-97.
• [28] Ragaglitazar: the pharmacokinetics, pharmacodynamics, and tolerability of a novel dual PPAR alpha and gamma agonist in healthy subjects and patients with type 2 diabetes. J Clin Pharmacol. 2003 Nov;43(11):1244-56.
• [29] Bezafibrate at clinically relevant doses decreases serum/liver triglycerides via down-regulation of sterol regulatory element-binding protein-1c in... Mol Pharmacol. 2009 Apr;75(4):782-92.
• [30] Pemafibrate: First Global Approval. Drugs. 2017 Oct;77(16):1805-1810.
• [31] Determination of chiglitazar, a dual alpha/gamma peroxisome proliferator-activated receptor (PPAR) agonist, in human plasma by liquid chromatograph... Pharmazie. 2007 Nov;62(11):825-9.
• [32] Tesaglitazar, a dual PPAR-/ agonist, hamster carcinogenicity, investigative animal and clinical studies.Toxicol Pathol.2012;40(1):18-32.
• [33] Dual peroxisome proliferator-activated receptor / agonist GFT505 improves hepatic and peripheral insulin sensitivity in abdominally obese subjects.Diabetes Care.2013 Oct;36(10):2923-30.
• [34] Pharmacokinetics, safety, and tolerability of saroglitazar (ZYH1), a predominantly PPARalpha agonist with moderate PPARgamma agonist activity in healthy human subjects. Clin Drug Investig. 2013 Nov;33(11):809-16.