Pemafibrate | (R)-K 13675 | CAS#848259-27-8 | PPAR alpha agonist

MedKoo Cat#: 206448 | Name: Pemafibrate

Description:

WARNING: This product is for research use only, not for human or veterinary use.

Pemafibrate, also known as (R)-K 13675, is a PPAR alpha agonist. (R)-K-13675 decreases the secretion of inflammatory markers without affecting cell proliferation or tube formation. Peroxisome proliferator-activated receptor-alpha (PPAR-alpha) is a key regulator of lipid and glucose metabolism and has been implicated in inflammation. (R)-K-13675 was associated with the inhibition of inflammatory responses without affecting cell proliferation or angiogenesis, and subsequently may induce an anti-atherosclerotic effect.

Chemical Structure

Pemafibrate

CAS#848259-27-8 (free acid)

Theoretical Analysis

MedKoo Cat#: 206448

Name: Pemafibrate

CAS#: 848259-27-8 (free acid)

Chemical Formula: C28H30N2O6

Exact Mass: 490.2104

Molecular Weight: 490.56

Elemental Analysis: C, 68.56; H, 6.16; N, 5.71; O, 19.57

Price and Availability

Size	Price	Availability
5mg	USD 150.00	Ready to ship
10mg	USD 250.00	Ready to ship
25mg	USD 550.00	Ready to ship
50mg	USD 950.00	Ready to ship
100mg	USD 1,650.00	Ready to ship
200mg	USD 2,650.00	Ready to Ship

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Related CAS #

950644-31-2 (sodium) 848259-27-8 (free acid)

Synonym

K-877; K877; K 877; (R)-K 13675; (R)-K13675; (R)K-13675; Pemafibrate

IUPAC/Chemical Name

(R)-2-(3-((benzo[d]oxazol-2-yl(3-(4-methoxyphenoxy)propyl)amino)methyl)phenoxy)butanoic acid

InChi Key

ZHKNLJLMDFQVHJ-RUZDIDTESA-N

InChi Code

InChI=1S/C28H30N2O6/c1-3-25(27(31)32)35-23-9-6-8-20(18-23)19-30(28-29-24-10-4-5-11-26(24)36-28)16-7-17-34-22-14-12-21(33-2)13-15-22/h4-6,8-15,18,25H,3,7,16-17,19H2,1-2H3,(H,31,32)/t25-/m1/s1

SMILES Code

CC[C@@H](OC1=CC=CC(CN(C2=NC3=CC=CC=C3O2)CCCOC4=CC=C(OC)C=C4)=C1)C(O)=O

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO, not in water

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#S7S12C08

QC Data

View QC data: current batch, Lot#S7S12C08

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Pemafibrate is a selective antagonist of peroxisome proliferator-activated receptor α (PPARα; EC50 = 1 nM for transcriptional activity), a transcription factor that is essential for regulation of lipid homostasis, and is selective for PPARα over PPARδ and PPARγ (EC50 = 2,300 and 1,000 nM, respectively, for transcriptional activity).

In vitro activity:

Under HG + H/R conditions, NF-κB protein expression levels were significantly enhanced in H9c2 cells compared with those in the control group (P<0.001; Fig. 4A). Pemafibrate significantly suppressed the protein expression levels of NF-κB compared with those in the HG + H/R group (P<0.001; Fig. 4A). To evaluate whether pemafibrate may regulate mitochondrial dysfunction and apoptosis through the NF-κB signaling pathway, NF-κB was overexpressed in H9c2 cells (P<0.001; Fig. 4B). The results demonstrated that overexpression of NF-κB reversed the pemafibrate-induced increase in ATP levels in the HG + H/R treatment group (P<0.01 vs. pemafibrate + HG + H/R and pemafibrate + HG + H/R + NC; Fig. 4C). Pemafibrate decreased the expression levels of cleavedcaspase-3 compared with those in the HG + H/R group; however, overexpression of NF-κB reversed this effect (P<0.01 vs. pemafibrate + HG + H/R and pemafibrate + HG + H/R + NC; Fig. 4D), indicating that pemafibrate inhibited the HG + H/R-induced apoptosis by regulating the NF-κB signaling pathway. However, overexpression of NF-κB expression failed to significantly reverse the pemafibrate-induced reduction in Cyt-c expression levels (Fig. 4D). These results suggest that pemafibrate may prevent mitochondrial dysfunction by interacting with the NF-κB signaling pathway. Exp Ther Med. 2021 Apr; 21(4): 331. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7903427/

In vivo activity:

To verify the effect of pemafibrate on STAM mouse livers, a comprehensive transcriptome analysis was performed by RNA-seq using liver tissues collected from normal, STAM control, and pemafibrate-treated STAM mice. 187 up-regulated and 477 down-regulated genes were identified in the pemafibrate-treated compared with the STAM control group by our stringent criteria (Supplementary Table 1). In fact, PPARα–regulated FAO-related genes were significantly induced in the pemafibrate-treated group (Supplementary Fig. 1). The expression levels of genes related to TG hydrolysis, fatty acid uptake, fatty acid activation, fatty acid binding, peroxisomal and mitochondrial oxidation, and ketogenesis were higher in the STAM control group than in the normal group (Supplementary Figs. 1 and 2). Pemafibrate apparently induced the expression of these genes. In particular, pemafibrate treatment resulted in the greatest increase in Pdk4 expression, suggesting that it mediates the suppression of glucose oxidation and preferential activation of fatty acid oxidation (Supplementary Figs. 1 and 2). Pemafibrate did not influence glycolysis and Pck1 expression but significantly induced a series of genes involved in TG synthesis from DHAP and glycerol (Fig. 2E,F). Pemafibrate had the greatest effect on Mogat1, which has key roles in TG re-esterification from monoacylglycerols and diacylglycerols generated by TG hydrolysis24 in STAM mouse livers (Fig. 2E,F). These results suggest that pemafibrate enhances TG synthesis from DHAP and glycerol and the re-esterification of glycerol generated by TG hydrolysis in STAM mouse livers. Sci Rep. 2020; 10: 7818. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7210999/

	Solvent	mg/mL	mM
Solubility
	DMSO	30.0	61.20

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 490.56 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Li W, Xu J, Guo X, Xia X, Sun Y. Pemafibrate suppresses oxidative stress and apoptosis under cardiomyocyte ischemiareperfusion injury in type 1 diabetes mellitus. Exp Ther Med. 2021 Apr;21(4):331. doi: 10.3892/etm.2021.9762. Epub 2021 Feb 8. PMID: 33732304; PMCID: PMC7903427. 2. Horikawa T, Kawanami T, Hamaguchi Y, Tanaka Y, Kita S, Ryorin R, Takashi Y, Takahashi H, Tanabe M, Yanase T, Kawanami D, Nomiyama T. Pemafibrate, a PPAR alpha agonist, attenuates neointima formation after vascular injury in mice fed normal chow and a high-fat diet. Heliyon. 2020 Nov 6;6(11):e05431. doi: 10.1016/j.heliyon.2020.e05431. PMID: 33204884; PMCID: PMC7653074. 3. Sasaki Y, Asahiyama M, Tanaka T, Yamamoto S, Murakami K, Kamiya W, Matsumura Y, Osawa T, Anai M, Fruchart JC, Aburatani H, Sakai J, Kodama T. Pemafibrate, a selective PPARα modulator, prevents non-alcoholic steatohepatitis development without reducing the hepatic triglyceride content. Sci Rep. 2020 May 8;10(1):7818. doi: 10.1038/s41598-020-64902-8. PMID: 32385406; PMCID: PMC7210999. 4. Tomita Y, Ozawa N, Miwa Y, Ishida A, Ohta M, Tsubota K, Kurihara T. Pemafibrate Prevents Retinal Pathological Neovascularization by Increasing FGF21 Level in a Murine Oxygen-Induced Retinopathy Model. Int J Mol Sci. 2019 Nov 23;20(23):5878. doi: 10.3390/ijms20235878. PMID: 31771164; PMCID: PMC6928689

In vitro protocol:

In vivo protocol:

1. Sasaki Y, Asahiyama M, Tanaka T, Yamamoto S, Murakami K, Kamiya W, Matsumura Y, Osawa T, Anai M, Fruchart JC, Aburatani H, Sakai J, Kodama T. Pemafibrate, a selective PPARα modulator, prevents non-alcoholic steatohepatitis development without reducing the hepatic triglyceride content. Sci Rep. 2020 May 8;10(1):7818. doi: 10.1038/s41598-020-64902-8. PMID: 32385406; PMCID: PMC7210999. 2. Tomita Y, Ozawa N, Miwa Y, Ishida A, Ohta M, Tsubota K, Kurihara T. Pemafibrate Prevents Retinal Pathological Neovascularization by Increasing FGF21 Level in a Murine Oxygen-Induced Retinopathy Model. Int J Mol Sci. 2019 Nov 23;20(23):5878. doi: 10.3390/ijms20235878. PMID: 31771164; PMCID: PMC6928689

1: Dai W, Lv Q, Li Q, Fu L, Zhang Y, Zhang Y, Liu L, Tanigawa R, Kunitomi K, Kamei R, Suganami H, Ma C. Efficacy and Safety of Pemafibrate, a Novel Selective PPARα Modulator in Chinese Patients with Dyslipidemia: A Double-Masked, Randomized, Placebo- and Active-Controlled Comparison Trial. J Atheroscler Thromb. 2024 Aug 2. doi: 10.5551/jat.64112. Epub ahead of print. PMID: 39098034. 2: Fruchart JC, Fruchart-Najib J, Yamashita S, Libby P, Yokote K, Kodama T, Tomita Y, Ridker PM, Hermans MP, Zambon A. Lessons from PROMINENT and prospects for pemafibrate. Cardiovasc Diabetol. 2024 Jul 29;23(1):279. doi: 10.1186/s12933-024-02305-z. PMID: 39080716; PMCID: PMC11288121. 3: Kamimura T, Hounslow N, Suganami H, Tanigawa R. Drug-drug interactions between pemafibrate and statins on pharmacokinetics in healthy male volunteers: Open-label, randomized, 6-sequence, 3-period crossover studies. Clin Transl Sci. 2024 Aug;17(8):e13900. doi: 10.1111/cts.13900. PMID: 39078149; PMCID: PMC11287820. 4: Imai M, Liu S, Yano A, Suzuki Y, Mogi M, Sugiyama T. Feasibility and efficacy of pemafibrate for prevention of maternal high-fat intake-induced glucose metabolic dysfunction in offspring. Biochem Pharmacol. 2024 Jul 26;227:116454. doi: 10.1016/j.bcp.2024.116454. Epub ahead of print. PMID: 39069137. 5: Ueda H, Mineo R, Sugiyama T, Koseki M, Itoh Y, Iwamoto R, Tamba S, Yamamoto K, Yamada Y, Hiraoka H, Matsuzawa Y. A Man with Primary Hyperchylomicronemia with Triglyceride Levels Exceeding 11,000 mg/dL was Well Controlled by Pemafibrate Combined with Dietary Therapy: A Case Report. Intern Med. 2024 Jul 25. doi: 10.2169/internalmedicine.3946-24. Epub ahead of print. PMID: 39048362. 6: Marinho LL, Everett BM, Aday AW, Visseren FLJ, MacFadyen JG, Zaharris E, Plutzky J, Santos RD, Libby P, Fruchart JC, Ridker PM, Pradhan AD. Effect of Pemafibrate on Diabetic Foot Ulceration and Gangrene: An Exploratory Analysis From PROMINENT. J Am Coll Cardiol. 2024 Jul 23;84(4):408-410. doi: 10.1016/j.jacc.2024.05.028. PMID: 39019534. 7: Bentanachs R, Miró L, Sánchez RM, Ramírez-Carrasco P, Amat C, Alegret M, Pérez A, Roglans N, Laguna JC. Pemafibrate abrogates SLD in a rat experimental dietary model, inducing a shift in fecal bile acids and microbiota composition. Biomed Pharmacother. 2024 Aug;177:117067. doi: 10.1016/j.biopha.2024.117067. Epub 2024 Jun 29. PMID: 38943989. 8: Akasaki Y. Once-daily Extended-Release Pemafibrate Enhances Adherence and Triglyceride Control Over Twice-Daily Dosing. J Atheroscler Thromb. 2024 Jun 27. doi: 10.5551/jat.ED266. Epub ahead of print. PMID: 38925925. 9: Shinozaki H, Kawai S, Gamo-Kawasaki M, Takei A, Tsujikado K, Fukuda K, Yamauchi M, Hara K, Tsuchiya T, Takebayashi K, Hashimoto K. Analysis of serum levels and DNA methylation of fibroblast growth factor 21 using peripheral blood-derived genomes in patients with obesity. Endocr J. 2024 Jun 21. doi: 10.1507/endocrj.EJ23-0570. Epub ahead of print. PMID: 38910123. 10: Iwadare T, Kimura T, Kunimoto H, Okumura T, Wakabayashi SI, Kobayashi H, Yamashita Y, Sugiura A, Tanaka N, Umemura T. Long-Term pemafibrate treatment exhibits limited impact on body fat mass in patients with hypertriglyceridemia accompanying NAFLD. Front Endocrinol (Lausanne). 2024 May 17;15:1329294. doi: 10.3389/fendo.2024.1329294. PMID: 38828415; PMCID: PMC11140089. 11: Sumida Y, Toyoda H, Yasuda S, Kimoto S, Sakamoto K, Nakade Y, Ito K, Osonoi T, Yoneda M. Comparison of Efficacy between Pemafibrate and Omega-3-Acid Ethyl Ester in the Liver: the PORTRAIT Study. J Atheroscler Thromb. 2024 May 21. doi: 10.5551/jat.64896. Epub ahead of print. PMID: 38777770. 12: Ota T, Soga K, Hayakawa F, Yamaguchi M, Tamano M. Utility of pemafibrate in nonalcoholic steatohepatitis model mice induced by a choline-deficient, high-fat diet and dextran sulfate sodium. Biochem Biophys Rep. 2024 May 3;38:101724. doi: 10.1016/j.bbrep.2024.101724. PMID: 38737727; PMCID: PMC11088230. 13: Shima H, Tashiro M, Inoue T, Okada K, Okamoto T, Wariishi S, Doi T, Minakuchi J. Clinical Efficacy and Safety of Low-Dose Pemafibrate in Patients With Severe Renal Impairment: A Retrospective Study. Cureus. 2024 Apr 7;16(4):e57777. doi: 10.7759/cureus.57777. PMID: 38715994; PMCID: PMC11076059. 14: Doi T, Langsted A, Nordestgaard BG. Remnant cholesterol, LDL cholesterol, and apoB absolute mass changes explain results of the PROMINENT trial. Atherosclerosis. 2024 Jun;393:117556. doi: 10.1016/j.atherosclerosis.2024.117556. Epub 2024 Apr 20. PMID: 38678642. 15: Yamashita S, Hirano T, Shimano H, Tsukamoto K, Yoshida M, Yoshida H. Managing hypertriglyceridemia for cardiovascular disease prevention: Lessons from the PROMINENT trial. Eur J Clin Invest. 2024 Apr 25:e14227. doi: 10.1111/eci.14227. Epub ahead of print. PMID: 38662591. 16: Arai H, Yamashita S, Araki E, Yokote K, Tanigawa R, Saito A, Yamasaki S, Suganami H, Ishibashi S. Efficacy and Safety of Pemafibrate Extended-Release Tablet: a Phase 3, Multicenter, Randomized, Double-Blind, Active-Controlled, Parallel-Group Comparison Trial. J Atheroscler Thromb. 2024 Apr 13. doi: 10.5551/jat.64677. Epub ahead of print. PMID: 38616112. 17: Ono H, Atsukawa M, Tsubota A, Arai T, Suzuki K, Higashi T, Kitamura M, Shioda-Koyano K, Kawano T, Yoshida Y, Okubo T, Hayama K, Itokawa N, Kondo C, Nagao M, Iwabu M, Iwakiri K. Impact of pemafibrate in patients with metabolic dysfunction-associated steatotic liver disease complicated by dyslipidemia: A single-arm prospective study. JGH Open. 2024 Apr 2;8(4):e13057. doi: 10.1002/jgh3.13057. PMID: 38572327; PMCID: PMC10986296. 18: Kamata S, Honda A, Kashiwagi N, Shimamura A, Yashiro S, Komori Y, Hosoda A, Akahoshi N, Ishii I. Different Coactivator Recruitment to Human PPARα/δ/γ Ligand-Binding Domains by Eight PPAR Agonists to Treat Nonalcoholic Fatty Liver Disease. Biomedicines. 2024 Mar 11;12(3):624. doi: 10.3390/biomedicines12030624. PMID: 38540237; PMCID: PMC10967972. 19: Iwasa M, Sugimoto R, Eguchi A, Tamai Y, Shigefuku R, Fujiwara N, Tanaka H, Kobayashi Y, Ikoma J, Kaito M, Nakagawa H. Effectiveness of 1-year pemafibrate treatment on steatotic liver disease: the influence of alcohol consumption. Eur J Gastroenterol Hepatol. 2024 Jun 1;36(6):793-801. doi: 10.1097/MEG.0000000000002766. Epub 2024 Mar 21. PMID: 38526942. 20: Ishida E, Horiguchi K, Matsumoto S, Ozawa A, Sekiguchi S, Yamada E. Influence of diet and body weight in treatment-resistant acquired partial lipodystrophy after hematopoietic stem cell transplantation and its potential for metabolic improvement. Diabetol Int. 2023 Dec 11;15(2):290-296. doi: 10.1007/s13340-023-00674-6. PMID: 38524924; PMCID: PMC10959909.