Synonym
Hymeglusin; L-659,699; L 659,699; L659,699.
IUPAC/Chemical Name
(2E,4E,7R)-11-[(2R,3R)-3-(hydroxymethyl)-4-oxooxetan-2-yl]-3,5,7-trimethylundeca-2,4-dienoic acid
InChi Key
ODCZJZWSXPVLAW-KXCGKLMDSA-N
InChi Code
InChI=1S/C18H28O5/c1-12(8-13(2)9-14(3)10-17(20)21)6-4-5-7-16-15(11-19)18(22)23-16/h9-10,12,15-16,19H,4-8,11H2,1-3H3,(H,20,21)/b13-9+,14-10+/t12-,15-,16-/m1/s1
SMILES Code
O=C(O)/C=C(C)/C=C(C)/C[C@H](C)CCCC[C@H]([C@H]1CO)OC1=O
Purity
>95% (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
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
Biological target:
Hymeglusin, as a fungal β-lactone Antibiotic, is a HMG-CoA synthase inhibitor (IC50 = 0.12 μM).
In vitro activity:
Hymeglusin decreased BCL2 expression levels in HL-60 and KG-1 cells.
Reference: Front Oncol. 2022 Jun 29;12:864430. https://pubmed.ncbi.nlm.nih.gov/35847946/
In vivo activity:
Inhibition of β-hydroxy-β-methylglutaryl (HMG)-CoA synthase (HMGCS2) with hymeglusin lowered ischaemic β-OHB accumulation by 40%, despite increased flux through succinyl-CoA-3-oxaloacid CoA transferase (SCOT), resulting in greater contractile recovery. Hymeglusin also protected cardiac mitochondrial respiratory capacity during ischaemia/reperfusion in rats.
Reference: Elife. 2021 Sep 7;10:e71270. https://pubmed.ncbi.nlm.nih.gov/34491199/
Preparing Stock Solutions
The following data is based on the
product
molecular weight
324.42
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. Zhou C, Wang Z, Yang S, Li H, Zhao L. Hymeglusin Enhances the Pro-Apoptotic Effects of Venetoclax in Acute Myeloid Leukemia. Front Oncol. 2022 Jun 29;12:864430. doi: 10.3389/fonc.2022.864430. PMID: 35847946; PMCID: PMC9277771.
2. Skaff DA, Ramyar KX, McWhorter WJ, Barta ML, Geisbrecht BV, Miziorko HM. Biochemical and structural basis for inhibition of Enterococcus faecalis hydroxymethylglutaryl-CoA synthase, mvaS, by hymeglusin. Biochemistry. 2012 Jun 12;51(23):4713-22. doi: 10.1021/bi300037k. Epub 2012 May 25. PMID: 22510038; PMCID: PMC3431454.
3. Lindsay RT, Dieckmann S, Krzyzanska D, Manetta-Jones D, West JA, Castro C, Griffin JL, Murray AJ. β-hydroxybutyrate accumulates in the rat heart during low-flow ischaemia with implications for functional recovery. Elife. 2021 Sep 7;10:e71270. doi: 10.7554/eLife.71270. PMID: 34491199; PMCID: PMC8423437.
4. Tomoda H, Ohbayashi N, Morikawa Y, Kumagai H, Omura S. Binding site for fungal beta-lactone hymeglusin on cytosolic 3-hydroxy-3-methylglutaryl coenzyme A synthase. Biochim Biophys Acta. 2004 Feb 27;1636(1):22-8. doi: 10.1016/j.bbalip.2003.11.005. PMID: 14984735.
In vitro protocol:
1. Zhou C, Wang Z, Yang S, Li H, Zhao L. Hymeglusin Enhances the Pro-Apoptotic Effects of Venetoclax in Acute Myeloid Leukemia. Front Oncol. 2022 Jun 29;12:864430. doi: 10.3389/fonc.2022.864430. PMID: 35847946; PMCID: PMC9277771.
2. Skaff DA, Ramyar KX, McWhorter WJ, Barta ML, Geisbrecht BV, Miziorko HM. Biochemical and structural basis for inhibition of Enterococcus faecalis hydroxymethylglutaryl-CoA synthase, mvaS, by hymeglusin. Biochemistry. 2012 Jun 12;51(23):4713-22. doi: 10.1021/bi300037k. Epub 2012 May 25. PMID: 22510038; PMCID: PMC3431454.
In vivo protocol:
1. Lindsay RT, Dieckmann S, Krzyzanska D, Manetta-Jones D, West JA, Castro C, Griffin JL, Murray AJ. β-hydroxybutyrate accumulates in the rat heart during low-flow ischaemia with implications for functional recovery. Elife. 2021 Sep 7;10:e71270. doi: 10.7554/eLife.71270. PMID: 34491199; PMCID: PMC8423437.
2. Tomoda H, Ohbayashi N, Morikawa Y, Kumagai H, Omura S. Binding site for fungal beta-lactone hymeglusin on cytosolic 3-hydroxy-3-methylglutaryl coenzyme A synthase. Biochim Biophys Acta. 2004 Feb 27;1636(1):22-8. doi: 10.1016/j.bbalip.2003.11.005. PMID: 14984735.
1: Skaff DA, Ramyar KX, McWhorter WJ, Barta ML, Geisbrecht BV, Miziorko HM. Biochemical and structural basis for inhibition of Enterococcus faecalis hydroxymethylglutaryl-CoA synthase, mvaS, by hymeglusin. Biochemistry. 2012 Jun 12;51(23):4713-22. doi: 10.1021/bi300037k. PubMed PMID: 22510038; PubMed Central PMCID: PMC3431454.
2: Carazo A, Alejandre MJ, Louktibi A, Linares A. The reversal of the inhibition on lipids synthesis by L-659,699 in arterial smooth muscle cells cultures. Mol Cell Biochem. 2001 May;221(1-2):25-31. PubMed PMID: 11506182.
3: Ginger ML, Chance ML, Sadler IH, Goad LJ. The biosynthetic incorporation of the intact leucine skeleton into sterol by the trypanosomatid Leishmania mexicana. J Biol Chem. 2001 Apr 13;276(15):11674-82. PubMed PMID: 11148203.
4: Rokosz LL, Boulton DA, Butkiewicz EA, Sanyal G, Cueto MA, Lachance PA, Hermes JD. Human cytoplasmic 3-hydroxy-3-methylglutaryl coenzyme A synthase: expression, purification, and characterization of recombinant wild-type and Cys129 mutant enzymes. Arch Biochem Biophys. 1994 Jul;312(1):1-13. PubMed PMID: 7913309.
5: Giron MD, Havel CM, Watson JA. Isopentenoid synthesis in eukaryotic cells. An initiating role for post-translational control of 3-hydroxy-3-methylglutaryl coenzyme A reductase. Arch Biochem Biophys. 1993 Apr;302(1):265-71. PubMed PMID: 8097083.
6: Greenspan MD, Bull HG, Yudkovitz JB, Hanf DP, Alberts AW. Inhibition of 3-hydroxy-3-methylglutaryl-CoA synthase and cholesterol biosynthesis by beta-lactone inhibitors and binding of these inhibitors to the enzyme. Biochem J. 1993 Feb 1;289 ( Pt 3):889-95. PubMed PMID: 8094614; PubMed Central PMCID: PMC1132259.
7: Greenspan MD, Yudkovitz JB, Lo CY, Chen JS, Alberts AW, Hunt VM, Chang MN, Yang SS, Thompson KL, Chiang YC, et al. Inhibition of hydroxymethylglutaryl-coenzyme A synthase by L-659,699. Proc Natl Acad Sci U S A. 1987 Nov;84(21):7488-92. PubMed PMID: 2890166; PubMed Central PMCID: PMC299321.
