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

General Information of Drug (ID: DM67P0F)

• Drug Name: CS-038 Drug Info
• Synonyms: Chiglitazar; CS-00098; PPAR alpha/gamma agonist (diabetes), Chipscreen Biosciences

Indication

Disease Entry	ICD 11	Status	REF
Type-2 diabetes	5A11	Phase 3	[1]

• Cross-matching ID:
  PubChem CID: 71402018
  CAS Number: CAS 743438-45-1
  TTD Drug ID: DM67P0F

Molecule-Related Drug Atlas

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	[4]
Pioglitazone	DMKJ485	Amyotrophic lateral sclerosis	8B60.0	Approved	[5]
Lobeglitazone	DMHY3IP	Type-2 diabetes	5A11	Approved	[6]
Rosiglitazone XR	DMT45MU	Type-2 diabetes	5A11	Approved	[7]
Thiazolidinedione	DMC1NBW	Alzheimer disease	8A20	Approved	[5]
Glitazone	DMDN4A1	N. A.	N. A.	Phase 4	[8]
MURAGLITAZAR	DMG3NFZ	N. A.	N. A.	Phase 3	[9]
Rivoglitazone	DMBY31K	Ocular inflammation	9C61.24	Phase 3	[10]
Balaglitazone	DMXBHR6	Type-1 diabetes	5A10	Phase 3	[11]
Ragaglitazar	DMFSHEM	Type-1 diabetes	5A10	Phase 3	[12]

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

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Lobeglitazone	DMHY3IP	Type-2 diabetes	5A11	Approved	[6]
Fenofibrate	DMFKXDY	Coronary atherosclerosis		Approved	[8]
Bezafibrate	DMZDCS0	Hypercholesterolaemia	5C80.0	Approved	[13]
Ciprofibrate	DMGC5DB	Hyperlipoproteinemia	5C80	Approved	[8]
Pemafibrate	DMD1VZL	Hyperlipidemia	5C80.Z	Approved	[14]
MURAGLITAZAR	DMG3NFZ	N. A.	N. A.	Phase 3	[9]
Ragaglitazar	DMFSHEM	Type-1 diabetes	5A10	Phase 3	[12]
TESAGLITAZAR	DMGRBN5	Type-1 diabetes	5A10	Phase 3	[15]
GFT-505	DM7ZOAE	Non-alcoholic steatohepatitis	DB92.1	Phase 3	[16]
ZYH-1	DMMBJYC	Lipid metabolism disorder	5C52.Z	Phase 3	[17]

Drug(s) Affected By Hepatic triacylglycerol lipase (LIPC)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Quercetin	DM3NC4M	Obesity	5B81	Approved	[18]
obeticholic acid	DM3Q1SM	Primary biliary cholangitis	DB96.1	Approved	[19]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[20]
Isotretinoin	DM4QTBN	Acne vulgaris	ED80	Approved	[21]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[22]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[23]
Rosiglitazone	DMILWZR	Chronic kidney disease	GB61	Approved	[3]
Cupric Sulfate	DMP0NFQ	Fungal infection	1F29-1F2F	Approved	[24]
Arsenic	DMTL2Y1	N. A.	N. A.	Approved	[25]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[26]

Drug(s) Affected By Peroxisomal acyl-coenzyme A oxidase 1 (ACOX1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
obeticholic acid	DM3Q1SM	Primary biliary cholangitis	DB96.1	Approved	[19]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[20]
Testosterone	DM7HUNW	Hot flushes	GA30	Approved	[27]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[22]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[23]
Ivermectin	DMDBX5F	Intestinal strongyloidiasis due to nematode parasite	1F6B	Approved	[28]
Fenofibrate	DMFKXDY	Coronary atherosclerosis		Approved	[29]
Ciprofibrate	DMGC5DB	Hyperlipoproteinemia	5C80	Approved	[30]
Capsaicin	DMGMF6V	Back pain	ME84.Z	Approved	[31]
Sodium Acetate Anhydrous	DMH21E0	Hyponatraemia	5C72	Approved	[32]

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	Modulator	[2]
Peroxisome proliferator-activated receptor gamma (PPAR-gamma)	TTZMAO3	PPARG_HUMAN	Modulator	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Hepatic triacylglycerol lipase (LIPC)	OTZY5SC9	LIPC_HUMAN	Gene/Protein Processing	[3]
Peroxisomal acyl-coenzyme A oxidase 1 (ACOX1)	OTM0A0DY	ACOX1_HUMAN	Gene/Protein Processing	[3]

References

• [1] ClinicalTrials.gov (NCT02173457) Study of Chiglitazar Compare With Sitagliptin in Type 2 Diabetes Patients. U.S. National Institutes of Health.
• [2] 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.
• [3] In Vitro and In Vivo Characterizations of Chiglitazar, a Newly Identified PPAR Pan-Agonist. PPAR Res. 2012;2012:546548. doi: 10.1155/2012/546548. Epub 2012 Oct 22.
• [4] 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.
• [5] Functional PPAR-gamma receptor is a novel therapeutic target for ACTH-secreting pituitary adenomas. Nat Med. 2002 Nov;8(11):1281-7.
• [6] 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.
• [7] Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
• [8] Peroxisome proliferator-activated receptor alpha activators improve insulin sensitivity and reduce adiposity. J Biol Chem. 2000 Jun 2;275(22):16638-42.
• [9] 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.
• [10] 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.
• [11] Balaglitazone: a second generation peroxisome proliferator-activated receptor (PPAR) gamma () agonist.Mini Rev Med Chem.2012 Feb;12(2):87-97.
• [12] 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.
• [13] 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.
• [14] Pemafibrate: First Global Approval. Drugs. 2017 Oct;77(16):1805-1810.
• [15] Tesaglitazar, a dual PPAR-/ agonist, hamster carcinogenicity, investigative animal and clinical studies.Toxicol Pathol.2012;40(1):18-32.
• [16] 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.
• [17] 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.
• [18] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [19] Pharmacotoxicology of clinically-relevant concentrations of obeticholic acid in an organotypic human hepatocyte system. Toxicol In Vitro. 2017 Mar;39:93-103.
• [20] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [21] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [22] 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.
• [23] Integrated 'omics analysis reveals new drug-induced mitochondrial perturbations in human hepatocytes. Toxicol Lett. 2018 Jun 1;289:1-13.
• [24] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [25] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [26] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [27] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [28] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [29] Linalool is a PPARalpha ligand that reduces plasma TG levels and rewires the hepatic transcriptome and plasma metabolome. J Lipid Res. 2014 Jun;55(6):1098-110.
• [30] Fish oil and fenofibrate prevented phosphorylation-dependent hepatic sortilin 1 degradation in Western diet-fed mice. J Biol Chem. 2014 Aug 8;289(32):22437-49. doi: 10.1074/jbc.M114.548933. Epub 2014 Jul 1.
• [31] Induction of the endoplasmic reticulum stress protein GADD153/CHOP by capsaicin in prostate PC-3 cells: a microarray study. Biochem Biophys Res Commun. 2008 Aug 8;372(4):785-91.
• [32] Transcriptional Regulation of Human Arylamine N-Acetyltransferase 2 Gene by Glucose and Insulin in Liver Cancer Cell Lines. Toxicol Sci. 2022 Nov 23;190(2):158-172. doi: 10.1093/toxsci/kfac103.