SB-204990 | CAS# 154566-12-8 | Prodrug of SB-201076

MedKoo Cat#: 551029 | Name: SB-204990

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Description:

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

SB-204990 is the prodrug of the potent ATP citrate-lyase inhibitor SB-201076. SB-204990 is an important enzyme in controlling substrate supply for lipid synthesis de novo and a potential enzyme target for hypolipidaemic intervention.

Chemical Structure

SB-204990

CAS#154566-12-8

Theoretical Analysis

MedKoo Cat#: 551029

Name: SB-204990

CAS#: 154566-12-8

Chemical Formula: C18H22Cl2O5

Exact Mass: 388.0844

Molecular Weight: 389.27

Elemental Analysis: C, 55.54; H, 5.70; Cl, 18.21; O, 20.55

Price and Availability

Size	Price	Availability
1mg	USD 350.00	2 Weeks
5mg	USD 600.00	2 Weeks
10mg	USD 800.00	2 Weeks

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Synonym

SB-204990; SB 204990; SB204990

IUPAC/Chemical Name

2-((3S,5R)-5-(6-(2,4-dichlorophenyl)hexyl)-3-hydroxy-2-oxotetrahydrofuran-3-yl)acetic acid

InChi Key

YTRNLFYTHYWDAU-KDOFPFPSSA-N

InChi Code

InChI=1S/C18H22Cl2O5/c19-13-8-7-12(15(20)9-13)5-3-1-2-4-6-14-10-18(24,11-16(21)22)17(23)25-14/h7-9,14,24H,1-6,10-11H2,(H,21,22)/t14-,18+/m1/s1

SMILES Code

O=C(O)C[C@]1(O)C(O[C@H](CCCCCCC2=CC=C(Cl)C=C2Cl)C1)=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, DMF, and ethanol

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

Instruction

View handling instruction

Biological target:

SB-204990 is the prodrug of SB-201076.

In vitro activity:

ATP citrate lyase inhibition by RNAi or SB-204990 limits in vitro proliferation and survival of tumor cells displaying aerobic glycolysis. Reference: Cancer Cell. 2005 Oct;8(4):311-21. https://pubmed.ncbi.nlm.nih.gov/16226706/

In vivo activity:

When administered orally or in the diet of rats, SB-204990 was absorbed and accumulated in the liver. After one week of dietary exposure at varying doses, SB-204990 led to a dose-dependent reduction in both plasma cholesterol (up to 46%) and triglyceride levels (up to 80%). In dogs, SB-204990 reduced plasma cholesterol (up to 23%) and triglyceride levels (up to 38%), with a preference for lowering low-density lipoprotein cholesterol over high-density lipoprotein cholesterol levels. Reference: Biochem J. 1998 Aug 15;334 ( Pt 1)(Pt 1):113-9. https://pubmed.ncbi.nlm.nih.gov/9693110/

	Solvent	mg/mL	mM
Solubility
	DMF	30.0	77.07
	DMSO	20.0	51.38
	Ethanol	1.0	2.57

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 389.27 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. Hatipoglu A, Menon D, Levy T, Frias MA, Foster DA. Inhibiting glutamine utilization creates a synthetic lethality for suppression of ATP citrate lyase in KRas-driven cancer cells. PLoS One. 2022 Oct 21;17(10):e0276579. doi: 10.1371/journal.pone.0276579. PMID: 36269753; PMCID: PMC9586366. 2. Hatzivassiliou G, Zhao F, Bauer DE, Andreadis C, Shaw AN, Dhanak D, Hingorani SR, Tuveson DA, Thompson CB. ATP citrate lyase inhibition can suppress tumor cell growth. Cancer Cell. 2005 Oct;8(4):311-21. doi: 10.1016/j.ccr.2005.09.008. PMID: 16226706. 3. Sola-García A, Cáliz-Molina MÁ, Espadas I, Petr M, Panadero-Morón C, González-Morán D, Martín-Vázquez ME, Narbona-Pérez ÁJ, López-Noriega L, Martínez-Corrales G, López-Fernández-Sobrino R, Carmona-Marin LM, Martínez-Force E, Yanes O, Vinaixa M, López-López D, Reyes JC, Dopazo J, Martín F, Gauthier BR, Scheibye-Knudsen M, Capilla-González V, Martín-Montalvo A. Metabolic reprogramming by Acly inhibition using SB-204990 alters glucoregulation and modulates molecular mechanisms associated with aging. Commun Biol. 2023 Mar 8;6(1):250. doi: 10.1038/s42003-023-04625-4. PMID: 36890357; PMCID: PMC9995519. 4. Pearce NJ, Yates JW, Berkhout TA, Jackson B, Tew D, Boyd H, Camilleri P, Sweeney P, Gribble AD, Shaw A, Groot PH. The role of ATP citrate-lyase in the metabolic regulation of plasma lipids. Hypolipidaemic effects of SB-204990, a lactone prodrug of the potent ATP citrate-lyase inhibitor SB-201076. Biochem J. 1998 Aug 15;334 ( Pt 1)(Pt 1):113-9. doi: 10.1042/bj3340113. PMID: 9693110; PMCID: PMC1219669.

In vitro protocol:

In vivo protocol:

1. Sola-García A, Cáliz-Molina MÁ, Espadas I, Petr M, Panadero-Morón C, González-Morán D, Martín-Vázquez ME, Narbona-Pérez ÁJ, López-Noriega L, Martínez-Corrales G, López-Fernández-Sobrino R, Carmona-Marin LM, Martínez-Force E, Yanes O, Vinaixa M, López-López D, Reyes JC, Dopazo J, Martín F, Gauthier BR, Scheibye-Knudsen M, Capilla-González V, Martín-Montalvo A. Metabolic reprogramming by Acly inhibition using SB-204990 alters glucoregulation and modulates molecular mechanisms associated with aging. Commun Biol. 2023 Mar 8;6(1):250. doi: 10.1038/s42003-023-04625-4. PMID: 36890357; PMCID: PMC9995519. 2. Pearce NJ, Yates JW, Berkhout TA, Jackson B, Tew D, Boyd H, Camilleri P, Sweeney P, Gribble AD, Shaw A, Groot PH. The role of ATP citrate-lyase in the metabolic regulation of plasma lipids. Hypolipidaemic effects of SB-204990, a lactone prodrug of the potent ATP citrate-lyase inhibitor SB-201076. Biochem J. 1998 Aug 15;334 ( Pt 1)(Pt 1):113-9. doi: 10.1042/bj3340113. PMID: 9693110; PMCID: PMC1219669.

1: Espadas I, Cáliz-Molina MÁ, López-Fernández-Sobrino R, Panadero-Morón C, Sola-García A, Soriano-Navarro M, Martínez-Force E, Venegas-Calerón M, Salas JJ, Martín F, Gauthier BR, Alfaro-Cervelló C, Martí-Aguado D, Capilla-González V, Martín-Montalvo A. Hydroxycitrate delays early mortality in mice and promotes muscle regeneration while inducing a rich hepatic energetic status. Aging Cell. 2024 Sep;23(9):e14205. doi: 10.1111/acel.14205. Epub 2024 May 17. PMID: 38760909; PMCID: PMC11488303. 2: Wang J, Du J, Wang Y, Song Y, Wu J, Wang T, Yu Z, Song B. CILP2 promotes hypertrophic scar through Snail acetylation by interaction with ACLY. Biochim Biophys Acta Mol Basis Dis. 2024 Jun;1870(5):167202. doi: 10.1016/j.bbadis.2024.167202. Epub 2024 Apr 24. PMID: 38670440. 3: Sola-García A, Cáliz-Molina MÁ, Espadas I, Petr M, Panadero-Morón C, González-Morán D, Martín-Vázquez ME, Narbona-Pérez ÁJ, López-Noriega L, Martínez-Corrales G, López-Fernández-Sobrino R, Carmona-Marin LM, Martínez-Force E, Yanes O, Vinaixa M, López-López D, Reyes JC, Dopazo J, Martín F, Gauthier BR, Scheibye-Knudsen M, Capilla-González V, Martín-Montalvo A. Metabolic reprogramming by Acly inhibition using SB-204990 alters glucoregulation and modulates molecular mechanisms associated with aging. Commun Biol. 2023 Mar 8;6(1):250. doi: 10.1038/s42003-023-04625-4. PMID: 36890357; PMCID: PMC9995519. 4: Zhan Z, Li A, Zhang W, Wu X, He J, Li Z, Li Y, Sun J, Zhang H. ATP-citrate lyase inhibitor improves ectopic lipid accumulation in the kidney in a db/db mouse model. Front Endocrinol (Lausanne). 2022 Dec 8;13:914865. doi: 10.3389/fendo.2022.914865. PMID: 36568100; PMCID: PMC9771989. 5: Hallows KR, Li H, Saitta B, Sepehr S, Huang P, Pham J, Wang J, Mancino V, Chung EJ, Pinkosky SL, Pastor-Soler NM. Beneficial effects of bempedoic acid treatment in polycystic kidney disease cells and mice. Front Mol Biosci. 2022 Nov 25;9:1001941. doi: 10.3389/fmolb.2022.1001941. PMID: 36504724; PMCID: PMC9730828. 6: Hatipoglu A, Menon D, Levy T, Frias MA, Foster DA. Inhibiting glutamine utilization creates a synthetic lethality for suppression of ATP citrate lyase in KRas-driven cancer cells. PLoS One. 2022 Oct 21;17(10):e0276579. doi: 10.1371/journal.pone.0276579. PMID: 36269753; PMCID: PMC9586366. 7: Huang SS, Tsai CH, Kuo CY, Li YS, Cheng SP. ACLY inhibitors induce apoptosis and potentiate cytotoxic effects of sorafenib in thyroid cancer cells. Endocrine. 2022 Oct;78(1):85-94. doi: 10.1007/s12020-022-03124-6. Epub 2022 Jun 27. PMID: 35761130. 8: Wei X, Shi J, Lin Q, Ma X, Pang Y, Mao H, Li R, Lu W, Wang Y, Liu P. Targeting ACLY Attenuates Tumor Growth and Acquired Cisplatin Resistance in Ovarian Cancer by Inhibiting the PI3K-AKT Pathway and Activating the AMPK-ROS Pathway. Front Oncol. 2021 Mar 17;11:642229. doi: 10.3389/fonc.2021.642229. Erratum in: Front Oncol. 2021 Sep 07;11:742374. doi: 10.3389/fonc.2021.742374. PMID: 33816292; PMCID: PMC8011496. 9: Carnie L, Abraham M, McNamara MG, Hubner RA, Valle JW, Lamarca A. Impact on prognosis of early weight loss during palliative chemotherapy in patients diagnosed with advanced pancreatic cancer. Pancreatology. 2020 Dec;20(8):1682-1688. doi: 10.1016/j.pan.2020.09.012. Epub 2020 Sep 14. PMID: 33046391. 10: Sanfilippo J, Ness M, Petscher Y, Rappaport L, Zuckerman B, Gaab N. Reintroducing Dyslexia: Early Identification and Implications for Pediatric Practice. Pediatrics. 2020 Jul;146(1):e20193046. doi: 10.1542/peds.2019-3046. Epub 2020 Jun 23. PMID: 32576595; PMCID: PMC7329249. 11: Feng X, Zhang L, Xu S, Shen AZ. ATP-citrate lyase (ACLY) in lipid metabolism and atherosclerosis: An updated review. Prog Lipid Res. 2020 Jan;77:101006. doi: 10.1016/j.plipres.2019.101006. Epub 2019 Sep 6. PMID: 31499095. 12: Birchenall KA, Welsh GI, López Bernal A. Metabolite Changes in Maternal and Fetal Plasma Following Spontaneous Labour at Term in Humans Using Untargeted Metabolomics Analysis: A Pilot Study. Int J Environ Res Public Health. 2019 Apr 30;16(9):1527. doi: 10.3390/ijerph16091527. PMID: 31052173; PMCID: PMC6539865. 13: Zhang C, Liu J, Huang G, Zhao Y, Yue X, Wu H, Li J, Zhu J, Shen Z, Haffty BG, Hu W, Feng Z. Cullin3-KLHL25 ubiquitin ligase targets ACLY for degradation to inhibit lipid synthesis and tumor progression. Genes Dev. 2016 Sep 1;30(17):1956-70. doi: 10.1101/gad.283283.116. PMID: 27664236; PMCID: PMC5066239. 14: Inoue N, Watanabe H, Okamura K, Kondo S, Kagami S. Are the equations for the creatinine-based estimated glomerular filtration rate applicable to the evaluation of renal function in Japanese children and adult patients receiving chemotherapy? Clin Exp Nephrol. 2015 Apr;19(2):298-308. doi: 10.1007/s10157-014-0976-z. Epub 2014 May 4. PMID: 24792810. 15: Chu KY, Lin Y, Hendel A, Kulpa JE, Brownsey RW, Johnson JD. ATP-citrate lyase reduction mediates palmitate-induced apoptosis in pancreatic beta cells. J Biol Chem. 2010 Oct 15;285(42):32606-15. doi: 10.1074/jbc.M110.157172. Epub 2010 Aug 7. PMID: 20693577; PMCID: PMC2952263. 16: Yang L, Wang DX, Zheng QY, Pan J, Huang ZT, Wang MX. Highly efficient and concise synthesis of both antipodes of SB204900, clausenamide, neoclausenamide, homoclausenamide and zeta-clausenamide. Implication of biosynthetic pathways of Clausena alkaloids. Org Biomol Chem. 2009 Jun 21;7(12):2628-34. doi: 10.1039/b901965k. Epub 2009 May 5. PMID: 19503939. 17: Yoo B. Impact of missing data on type 1 error rates in non-inferiority trials. Pharm Stat. 2010 Apr-Jun;9(2):87-99. doi: 10.1002/pst.378. PMID: 19408241. 18: Hatzivassiliou G, Zhao F, Bauer DE, Andreadis C, Shaw AN, Dhanak D, Hingorani SR, Tuveson DA, Thompson CB. ATP citrate lyase inhibition can suppress tumor cell growth. Cancer Cell. 2005 Oct;8(4):311-21. doi: 10.1016/j.ccr.2005.09.008. PMID: 16226706. 19: Michno A, Skibowska A, Raszeja-Specht A, Cwikowska J, Szutowicz A. The role of adenosine triphosphate citrate lyase in the metabolism of acetyl coenzyme a and function of blood platelets in diabetes mellitus. Metabolism. 2004 Jan;53(1):66-72. doi: 10.1016/j.metabol.2003.07.012. PMID: 14681844. 20: Pearce NJ, Yates JW, Berkhout TA, Jackson B, Tew D, Boyd H, Camilleri P, Sweeney P, Gribble AD, Shaw A, Groot PH. The role of ATP citrate-lyase in the metabolic regulation of plasma lipids. Hypolipidaemic effects of SB-204990, a lactone prodrug of the potent ATP citrate-lyase inhibitor SB-201076. Biochem J. 1998 Aug 15;334 ( Pt 1)(Pt 1):113-9. doi: 10.1042/bj3340113. PMID: 9693110; PMCID: PMC1219669.