BMS-309403 | CAS#300657-03-8 | FABP4 Inhibitor

MedKoo Cat#: 524464 | Name: BMS-309403

Description:

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

BMS-309403 is a potent and selective fatty acid binding protein 4, adipocyte (FABP4) inhibitor (Ki values are <2, 250 and 350 nM for FABP4, FABP3 and FABP5 respectively). It decreases fatty acid uptake in adipocytes in vitro and reduces atherosclerotic lesion area in a mouse model of atherosclerosis. BMS309403 is an aromatic biphenyl azol compound that competes with fatty acids for the binding pocket of A-FABP with high speciﬁcity.

Chemical Structure

BMS-309403

CAS#300657-03-8

Theoretical Analysis

MedKoo Cat#: 524464

Name: BMS-309403

CAS#: 300657-03-8

Chemical Formula: C31H26N2O3

Exact Mass: 474.1943

Molecular Weight: 474.55

Elemental Analysis: C, 78.46; H, 5.52; N, 5.90; O, 10.11

Price and Availability

Size	Price	Availability
10mg	USD 150.00	Ready to ship
25mg	USD 250.00	Ready to ship
50mg	USD 450.00	Ready to ship
100mg	USD 750.00	Ready to ship
200mg	USD 1,350.00	Ready to ship
500mg	USD 2,950.00	Ready to ship
1g	USD 4,250.00	Ready to ship
2g	USD 6,450.00	2-3 weeks

Bulk Inquiry

Buy Now

Add to Cart

Related CAS #

300657-03-8

Synonym

BMS-309403; BMS309403; BMS 309403.

IUPAC/Chemical Name

((2'-(5-Ethyl-3,4-diphenyl-1H-pyrazol-1-yl)-1,1'-biphenyl-3-yl)oxy)acetic acid

InChi Key

SJRVJRYZAQYCEE-UHFFFAOYSA-N

InChi Code

InChI=1S/C31H26N2O3/c1-2-27-30(22-12-5-3-6-13-22)31(23-14-7-4-8-15-23)32-33(27)28-19-10-9-18-26(28)24-16-11-17-25(20-24)36-21-29(34)35/h3-20H,2,21H2,1H3,(H,34,35)

SMILES Code

CCc1c(c(nn1c2ccccc2c3cccc(c3)OCC(=O)O)c4ccccc4)c5ccccc5

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#C8R07B31

View CoA: current batch, Lot#C20R11B25

QC Data

View QC data: current batch, Lot#C20R11B25

View QC data: current batch, Lot#C8R07B31

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

BMS-309403 is a selective adipocyte fatty acid binding protein (also known as FABP4, aP2) inhibitor with Kis of <2, 250, and 350 nM for FABP4, FABP3, and FABP5,

In vitro activity:

BMS309403 induced enhancement of glucose uptake was accompanied by activation of AMPK. To further evaluate whether AMPK is directly responsible for the BMS309403-induced glucose uptake in myotubes, C2C12 myotubes were pre-incubated with or without an AMPK inhibitor, compound C, before the addition of BMS309403. Insulin was also added alone or in combination with BMS309403 as a control. As shown in Figure 4A, either BMS309403 or insulin alone increased glucose uptake. Western blotting analysis confirmed that BMS309403 evoked phosphorylations of AMPKα, p38 and ACC were remarkably attenuated upon pretreatment with the compound C (Fig. 4B). Notably, an additive effect of BMS309403 with insulin on glucose uptake was observed (Fig. 4), suggesting that these two reagents work through distinct signaling pathways. More importantly, compound C significantly suppressed BMS309403 stimulated glucose uptake (Fig. 4). Taken together, these data indicated that BMS309403 stimulated glucose uptake via an AMPK-dependent pathway but independent of insulin signaling in C2C12 myotubes. Reference: PLoS One. 2012; 7(8): e44570. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3432117/

In vivo activity:

A 6 week treatment with the A-FABP inhibitor, BMS309403, started in 12 week-old mice. At 18 weeks of age, the body weight of wild-type, vehicle-treated and BMS309403-treated ApoE−/− mice was 28.1 ± 0.6, 25.7 ± 1.2 and 26.7 ± 0.7 g, respectively. The only significant effect of 6 weeks of treatment with BMS309403 was to reduce the triglyceride level. The mRNA expression of A-FABP was minimal in the aorta of 18 weeks old wild-type and 8 weeks old ApoE−/− mice, but it increased progressively in the aortic endothelial cell layer of ApoE−/− mice from 12 to 18 weeks of age (Figure 1). Chronic administration of BMS309403 (15 mg·kg−1·day−1; from 12 to 18 weeks of age) in ApoE−/− mice significantly improved the relaxations, maximal relaxation and EC50 to UK14304 (Figure 5; Table 2), acetylcholine (Figure 6; Table 2) and A23187 (except for the maximal relaxation; Figure 6; Table 2), compared with those obtained in aortae from age-matched, vehicle-treated ApoE−/− mice, without significantly affecting responses to sodium nitroprusside (Figure 5; Table 2). Chronic treatment with BMS309403 (15 mg·kg−1·day−1) for 6 weeks significantly increased the phosphorylated eNOS (Ser1177) and total eNOS but not the phosphorylated to total eNOS ratio in aortae of 18 weeks old ApoE−/−mice, compared with values in aortae from the vehicle-treated mice (Figure 8B). These findings suggest that pharmacological inhibition of A-FABP represents a viable strategy for treating endothelial dysfunction and atherosclerosis. Reference: Br J Pharmacol. 2011 Apr; 162(7): 1564–1576. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3057294/

	Solvent	mg/mL	mM
Solubility
	DMSO	67.0	141.19
	Ethanol	24.0	50.57

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 474.55 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. Lin W, Huang X, Zhang L, Chen D, Wang D, Peng Q, Xu L, Li J, Liu X, Li K, Ding K, Jin S, Li J, Wu D. BMS309403 stimulates glucose uptake in myotubes through activation of AMP-activated protein kinase. PLoS One. 2012;7(8):e44570. doi: 10.1371/journal.pone.0044570. Epub 2012 Aug 31. PMID: 22952994; PMCID: PMC3432117. 2. Okamura Y, Otani K, Sekiguchi A, Kogane T, Kakuda C, Sakamoto Y, Kodama T, Okada M, Yamawaki H. Vasculo-protective effect of BMS-309403 is independent of its specific inhibition of fatty acid-binding protein 4. Pflugers Arch. 2017 Sep;469(9):11771188. doi: 10.1007/s00424-017-1976-0. Epub 2017 Apr 13. PMID: 28405802. 3. Lee MY, Li H, Xiao Y, Zhou Z, Xu A, Vanhoutte PM. Chronic administration of BMS309403 improves endothelial function in apolipoprotein E-deficient mice and in cultured human endothelial cells. Br J Pharmacol. 2011 Apr;162(7):1564-76. doi: 10.1111/j.1476-5381.2010.01158.x. PMID: 21175571; PMCID: PMC3057294. 4. Gong Y, Yu Z, Gao Y, Deng L, Wang M, Chen Y, Li J, Cheng B. FABP4 inhibitors suppress inflammation and oxidative stress in murine and cell models of acute lung injury. Biochem Biophys Res Commun. 2018 Feb 19;496(4):1115-1121. doi: 10.1016/j.bbrc.2018.01.150. Epub 2018 Feb 1. PMID: 29409946.

In vitro protocol:

In vivo protocol:

1. Lee MY, Li H, Xiao Y, Zhou Z, Xu A, Vanhoutte PM. Chronic administration of BMS309403 improves endothelial function in apolipoprotein E-deficient mice and in cultured human endothelial cells. Br J Pharmacol. 2011 Apr;162(7):1564-76. doi: 10.1111/j.1476-5381.2010.01158.x. PMID: 21175571; PMCID: PMC3057294. 2. Gong Y, Yu Z, Gao Y, Deng L, Wang M, Chen Y, Li J, Cheng B. FABP4 inhibitors suppress inflammation and oxidative stress in murine and cell models of acute lung injury. Biochem Biophys Res Commun. 2018 Feb 19;496(4):1115-1121. doi: 10.1016/j.bbrc.2018.01.150. Epub 2018 Feb 1. PMID: 29409946.

1: Yao F, Li Z, Ehara T, Yang L, Wang D, Feng L, Zhang Y, Wang K, Shi Y, Duan H, Zhang L. Fatty Acid-Binding Protein 4 mediates apoptosis via endoplasmic reticulum stress in mesangial cells of diabetic nephropathy. Mol Cell Endocrinol. 2015 Aug 15;411:232-42. doi: 10.1016/j.mce.2015.05.003. Epub 2015 May 6. PubMed PMID: 25958041. 2: Boss M, Kemmerer M, Brüne B, Namgaladze D. FABP4 inhibition suppresses PPARγ activity and VLDL-induced foam cell formation in IL-4-polarized human macrophages. Atherosclerosis. 2015 Jun;240(2):424-30. doi: 10.1016/j.atherosclerosis.2015.03.042. Epub 2015 Apr 3. PubMed PMID: 25897794. 3: Wang Y, Lin HQ, Law WK, Liang WC, Zhang JF, Hu JS, Ip TM, Waye MM, Wan DC. Pimozide, a novel fatty acid binding protein 4 inhibitor, promotes adipogenesis of 3T3-L1 cells by activating PPARγ. ACS Chem Neurosci. 2015 Feb 18;6(2):211-8. doi: 10.1021/cn5002107. Epub 2014 Dec 3. PubMed PMID: 25437245. 4: Tyukhtenko S, Chan K, Jiang R, Zhou H, Mercier RW, Yang DP, Makriyannis A, Guo JJ. Hydrogen-bonded His93 as a sensitive probe for identifying inhibitors of the endocannabinoid transport protein FABP7. Chem Biol Drug Des. 2015 May;85(5):534-40. doi: 10.1111/cbdd.12440. Epub 2014 Oct 16. PubMed PMID: 25255720; PubMed Central PMCID: PMC4374022. 5: Sanson B, Wang T, Sun J, Wang L, Kaczocha M, Ojima I, Deutsch D, Li H. Crystallographic study of FABP5 as an intracellular endocannabinoid transporter. Acta Crystallogr D Biol Crystallogr. 2014 Feb;70(Pt 2):290-8. doi: 10.1107/S1399004713026795. Epub 2014 Jan 29. PubMed PMID: 24531463; PubMed Central PMCID: PMC3940194. 6: Kralisch S, Ebert T, Lossner U, Jessnitzer B, Stumvoll M, Fasshauer M. Adipocyte fatty acid-binding protein is released from adipocytes by a non-conventional mechanism. Int J Obes (Lond). 2014 Sep;38(9):1251-4. doi: 10.1038/ijo.2013.232. Epub 2013 Dec 13. PubMed PMID: 24445660. 7: Beniyama Y, Matsuno K, Miyachi H. Structure-guided design, synthesis and in vitro evaluation of a series of pyrazole-based fatty acid binding protein (FABP) 3 ligands. Bioorg Med Chem Lett. 2013 Mar 15;23(6):1662-6. doi: 10.1016/j.bmcl.2013.01.054. Epub 2013 Jan 26. PubMed PMID: 23395658. 8: Chan CK, Zhao Y, Liao SY, Zhang YL, Lee MY, Xu A, Tse HF, Vanhoutte PM. A-FABP and oxidative stress underlie the impairment of endothelium-dependent relaxations to serotonin and the intima-medial thickening in the porcine coronary artery with regenerated endothelium. ACS Chem Neurosci. 2013 Jan 16;4(1):122-9. doi: 10.1021/cn3000873. Epub 2012 Sep 22. PubMed PMID: 23336051; PubMed Central PMCID: PMC3547481. 9: Hoo RL, Lee IP, Zhou M, Wong JY, Hui X, Xu A, Lam KS. Pharmacological inhibition of adipocyte fatty acid binding protein alleviates both acute liver injury and non-alcoholic steatohepatitis in mice. J Hepatol. 2013 Feb;58(2):358-64. doi: 10.1016/j.jhep.2012.10.022. Epub 2012 Oct 26. PubMed PMID: 23108115. 10: Lin W, Huang X, Zhang L, Chen D, Wang D, Peng Q, Xu L, Li J, Liu X, Li K, Ding K, Jin S, Li J, Wu D. BMS309403 stimulates glucose uptake in myotubes through activation of AMP-activated protein kinase. PLoS One. 2012;7(8):e44570. doi: 10.1371/journal.pone.0044570. Epub 2012 Aug 31. PubMed PMID: 22952994; PubMed Central PMCID: PMC3432117. 11: Okada T, Hiromura M, Otsuka M, Enomoto S, Miyachi H. Synthesis of BMS-309403-related compounds, including [¹⁴C]BMS-309403, a radioligand for adipocyte fatty acid binding protein. Chem Pharm Bull (Tokyo). 2012;60(1):164-8. PubMed PMID: 22223390. 12: Look C, Morano I, Ehrhart-Bornstein M, Bornstein SR, Lamounier-Zepter V. BMS309403 directly suppresses cardiac contractile function. Naunyn Schmiedebergs Arch Pharmacol. 2011 Sep;384(3):255-63. doi: 10.1007/s00210-011-0667-1. Epub 2011 Jul 16. PubMed PMID: 21766159. 13: Tian Z, Zhao ZA, Liang XH, Zhang XH, Sha AG, Zhang ZR, Yu YS, Yang ZM. Expression and function of fatty acid-binding protein 4 during mouse decidualization. Fertil Steril. 2011 Jun 30;95(8):2749-52.e1-5. doi: 10.1016/j.fertnstert.2011.05.052. PubMed PMID: 21704217. 14: Suhre K, Römisch-Margl W, de Angelis MH, Adamski J, Luippold G, Augustin R. Identification of a potential biomarker for FABP4 inhibition: the power of lipidomics in preclinical drug testing. J Biomol Screen. 2011 Jun;16(5):467-75. doi: 10.1177/1087057111402200. Epub 2011 May 4. PubMed PMID: 21543640. 15: Scifres CM, Chen B, Nelson DM, Sadovsky Y. Fatty acid binding protein 4 regulates intracellular lipid accumulation in human trophoblasts. J Clin Endocrinol Metab. 2011 Jul;96(7):E1083-91. doi: 10.1210/jc.2010-2084. Epub 2011 Apr 27. PubMed PMID: 21525163; PubMed Central PMCID: PMC3135200. 16: Lee MY, Li H, Xiao Y, Zhou Z, Xu A, Vanhoutte PM. Chronic administration of BMS309403 improves endothelial function in apolipoprotein E-deficient mice and in cultured human endothelial cells. Br J Pharmacol. 2011 Apr;162(7):1564-76. doi: 10.1111/j.1476-5381.2010.01158.x. PubMed PMID: 21175571; PubMed Central PMCID: PMC3057294. 17: Furuhashi M, Tuncman G, Görgün CZ, Makowski L, Atsumi G, Vaillancourt E, Kono K, Babaev VR, Fazio S, Linton MF, Sulsky R, Robl JA, Parker RA, Hotamisligil GS. Treatment of diabetes and atherosclerosis by inhibiting fatty-acid-binding protein aP2. Nature. 2007 Jun 21;447(7147):959-65. Epub 2007 Jun 6. PubMed PMID: 17554340; PubMed Central PMCID: PMC4076119. 18: Wu Y, Zhao F, Paborji M. Effect of fill weight, capsule shell, and sinker design on the dissolution behavior of capsule formulations of a weak acid drug candidate BMS-309403. Pharm Dev Technol. 2003;8(4):379-83. PubMed PMID: 14601962.