Synonym
Phostriecin; Sultriecin
IUPAC/Chemical Name
5,6-Dihydro-5-hydroxy-6-(6-hydroxy-5-methyl-4-hydroxysulfonyloxyheptadec-1,7,9,11-tetraenyl)-2H-pyran-2-one
InChi Key
GGSVZPLREMJSBU-GGLGEDEXSA-N
InChi Code
InChI=1S/C23H34O8S/c1-3-4-5-6-7-8-9-10-11-13-19(24)18(2)21(31-32(27,28)29)14-12-15-22-20(25)16-17-23(26)30-22/h7-13,15-22,24-25H,3-6,14H2,1-2H3,(H,27,28,29)/b8-7+,10-9+,13-11+,15-12+
SMILES Code
O=C1C=CC(O)C(/C=C/CC(OS(=O)(O)=O)C(C)C(O)/C=C/C=C/C=C/CCCCC)O1
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
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:
Phostriecin is an antitumor antibiotic produced by Streptomyces pulveraceus. Phostriecin is a strong inhibitor of type 2A (PP2A) and a weak inhibitor of type 1 (PP1) serine/threonine protein phosphatases with IC50s of 3.2 nM and 131 μM.
In vitro activity:
Here, the effects of fostriecin (PP inhibitors) on the inhibition of histamine release from HLMC, on β-adrenoceptor-driven responses in mast cells and on desensitization were investigated. Long-term incubation (24 h) of mast cells with fostriecin (10-6 M) resulted in a significant (p < 0.001) reduction in the maximal response (from 41.2 [± 3.0] to 29.9 [± 4.2] %) to salbutamol following fostriecin treatment. The results showed that fostriecin pretreatment significantly attenuated the inhibitory effects of salbutamol.
Reference: J Immunotoxicol. 2017 Dec;14(1):60-65. https://pubmed.ncbi.nlm.nih.gov/28090813/
In vivo activity:
Fostriecin treatment alone augmented the SNP-evoked vasodilation, but did not influence vasodilatory responses to either SKA-31 or pinacidil. Quantification of these drug-evoked responses demonstrates that fostriecin treatment significantly enhanced the SNP-evoked vasodilation of rat cerebral arteries, without affecting responses to either SKA-31 or pinacidil (Figure 4(b)). Critically, further addition of penitrem-A selectively abolished the fostriecin-induced augmentation of SNP-evoked vasodilation, but did not influence responses to either SKA-31 or pinacidil. Notably, fostriecin exposure alone caused a slight inhibition of basal myogenic tone (i.e. increase in intraluminal diameter of 5.8 ± 1.9 μm, n = 5), which was reversed following the addition of the BK channel blocker penitrem-A.
Reference: J Cereb Blood Flow Metab. 2017 Dec;37(12):3759-3773. https://pubmed.ncbi.nlm.nih.gov/28155571/
Preparing Stock Solutions
The following data is based on the
product
molecular weight
470.58
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. Bastan R, Eskandari N, J Ardakani H, T Peachell P. Effects of fostriecin on β2-adrenoceptor-driven responses in human mast cells. J Immunotoxicol. 2017 Dec;14(1):60-65. doi: 10.1080/1547691X.2016.1259277. Epub 2017 Jan 16. PMID: 28090813.
2. Yu L, Xu J, Minobe E, Kameyama A, Yang L, Feng R, Hao L, Kameyama M. Role of protein phosphatases in the run down of guinea pig cardiac Cav1.2 Ca2+ channels. Am J Physiol Cell Physiol. 2016 May 15;310(10):C773-9. doi: 10.1152/ajpcell.00199.2015. Epub 2016 Jan 6. PMID: 26739491.
3. Kyle BD, Mishra RC, Braun AP. The augmentation of BK channel activity by nitric oxide signaling in rat cerebral arteries involves co-localized regulatory elements. J Cereb Blood Flow Metab. 2017 Dec;37(12):3759-3773. doi: 10.1177/0271678X17691291. Epub 2017 Feb 3. PMID: 28155571; PMCID: PMC5718322.
4. Walsh AH, Cheng A, Honkanen RE. Fostriecin, an antitumor antibiotic with inhibitory activity against serine/threonine protein phosphatases types 1 (PP1) and 2A (PP2A), is highly selective for PP2A. FEBS Lett. 1997 Oct 27;416(3):230-4. doi: 10.1016/s0014-5793(97)01210-6. PMID: 9373158.
In vitro protocol:
1. Bastan R, Eskandari N, J Ardakani H, T Peachell P. Effects of fostriecin on β2-adrenoceptor-driven responses in human mast cells. J Immunotoxicol. 2017 Dec;14(1):60-65. doi: 10.1080/1547691X.2016.1259277. Epub 2017 Jan 16. PMID: 28090813.
2. Yu L, Xu J, Minobe E, Kameyama A, Yang L, Feng R, Hao L, Kameyama M. Role of protein phosphatases in the run down of guinea pig cardiac Cav1.2 Ca2+ channels. Am J Physiol Cell Physiol. 2016 May 15;310(10):C773-9. doi: 10.1152/ajpcell.00199.2015. Epub 2016 Jan 6. PMID: 26739491.
In vivo protocol:
1. Kyle BD, Mishra RC, Braun AP. The augmentation of BK channel activity by nitric oxide signaling in rat cerebral arteries involves co-localized regulatory elements. J Cereb Blood Flow Metab. 2017 Dec;37(12):3759-3773. doi: 10.1177/0271678X17691291. Epub 2017 Feb 3. PMID: 28155571; PMCID: PMC5718322.
2. Walsh AH, Cheng A, Honkanen RE. Fostriecin, an antitumor antibiotic with inhibitory activity against serine/threonine protein phosphatases types 1 (PP1) and 2A (PP2A), is highly selective for PP2A. FEBS Lett. 1997 Oct 27;416(3):230-4. doi: 10.1016/s0014-5793(97)01210-6. PMID: 9373158.
1: Tanaka H, Kageyama K, Yoshimura N, Asada R, Kusumoto K, Miwa N. Anti-tumor and anti-invasive effects of diverse delta-alkyllactones: dependence on molecular side-chain length, action period and intracellular uptake. Life Sci. 2007 Apr 24;80(20):1851-5. Epub 2007 Feb 27. PubMed PMID: 17382354.
2: Burke CP, Swingle MR, Honkanen RE, Boger DL. Total synthesis and evaluation of phostriecin and key structural analogues. J Org Chem. 2010 Nov 19;75(22):7505-13. doi: 10.1021/jo1010203. Epub 2010 Jul 29. PubMed PMID: 20669916; PubMed Central PMCID: PMC2978778.
3: Burke CP, Haq N, Boger DL. Total synthesis, assignment of the relative and absolute stereochemistry, and structural reassignment of phostriecin (aka Sultriecin). J Am Chem Soc. 2010 Feb 24;132(7):2157-9. doi: 10.1021/ja9097252. PubMed PMID: 20108904; PubMed Central PMCID: PMC2824046.
4: Ohkuma H, Naruse N, Nishiyama Y, Tsuno T, Hoshino Y, Sawada Y, Konishi M, Oki T. Sultriecin, a new antifungal and antitumor antibiotic from Streptomyces roseiscleroticus. Production, isolation, structure and biological activity. J Antibiot (Tokyo). 1992 Aug;45(8):1239-49. PubMed PMID: 1399844.
Lawhorn BG, Boga SB, Wolkenberg SE, Colby DA, Gauss CM, Swingle MR, Amable L, Honkanen RE, Boger DL. Total synthesis and evaluation of cytostatin, its C10-C11 diastereomers, and additional key analogues: impact on PP2A inhibition. J Am Chem Soc. 2006 Dec 27;128(51):16720-32. doi: 10.1021/ja066477d. PMID: 17177422; PMCID: PMC2566737.
