HYPOTHEMYCIN
- CAS No.
- 76958-67-3
- Chemical Name:
- HYPOTHEMYCIN
- Synonyms
- f 152 D2;Nsc354462;Hypothemicin;HYPOTHEMYCIN;Hypothemycin - CAS 76958-67-3 - Calbiochem;(1aR,3S,4S,6Z,9S,15bR)-1a,8,9,15b-Tetrahydro-3,4,12-trihydroxy-14-methoxy-9-methyl-3H-oxireno[k][2]benzoxacyclotetradecin-5,11(2H,4H)-dione;(1aR,3S,4S,6Z,9S,15bR)-1a,8,9,15b-Tetrahydro-3,4,12-trihydroxy-9-methyl-14-methoxy-3H-oxireno[k][2]benzoxacyclotetradecin-5,11(2H,4H)-dione;(1aR,3S,4S,6Z,9S,15bR)-1a,2,4,5,11,8,9,15b-Octahydro-3,4,12-trihydroxy-9-methyl-14-methoxy-3H-oxireno[k][2]benzoxacyclotetradecin-5,11-dione;3H-Oxireno[k][2]benzoxacyclotetradecin-5,11(2H,4H)-dione,1a,8,9,15b-tetrahydro-3,4,12-trihydroxy-14-methoxy-9-methyl-,(1aR,3S,4S,6Z,9S,15bR)-
- CBNumber:
- CB3229169
- Molecular Formula:
- C19H22O8
- Molecular Weight:
- 378.37
- MDL Number:
- MFCD08457932
- MOL File:
- 76958-67-3.mol
- MSDS File:
- SDS
SAFETY
Risk and Safety Statements
| Symbol(GHS) |  GHS07 |
|||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Signal word | Warning | |||||||||
| Hazard statements | H302 | |||||||||
| Precautionary statements | P301+P312+P330 | |||||||||
| Hazard Codes | Xn | |||||||||
| Risk Statements | 22 | |||||||||
| WGK Germany | 3 | |||||||||
| HS Code | 29419000 | |||||||||
| NFPA 704 |
|
HYPOTHEMYCIN price More Price(14)
| Manufacturer | Product number | Product description | CAS number | Packaging | Price | Updated | Buy |
|---|---|---|---|---|---|---|---|
| Sigma-Aldrich | H1667 | Hypothemycin from Hypomyces trichothecoides, ≥98% (HPLC) | 76958-67-3 | 250μg | $221 | 2024-03-01 | Buy |
| Sigma-Aldrich | H1667 | Hypothemycin from | 76958-67-3 | 1mg | $679 | 2024-03-01 | Buy |
| Cayman Chemical | 27913 | Hypothemycin | 76958-67-3 | 1mg | $199 | 2024-03-01 | Buy |
| TRC | H998480 | Hypothemycin | 76958-67-3 | 5mg | $1620 | 2021-12-16 | Buy |
| Usbiological | 207223 | Hypothemycin | 76958-67-3 | 250ug | $342 | 2021-12-16 | Buy |
HYPOTHEMYCIN Chemical Properties,Uses,Production
Description
Hypothemycin (76958-67-3) is a potent and selective inhibitor of MEK.1-3?Acts via covalent binding to Cys residue.2?In cells, hypothemycin inhibits the MEK-ERK axis with sufficient selectivity to normalize transformed phenotypes3. Inhibits TNFα production in LPS-stimulated macrophages.4
Uses
Hypothemycin is a potent and selective inhibitor of threonine/tyrosine-specific kinase, MEK, and other protein kinases that contain a conserved cysteine residue in the ATP-binding site in in vitro studies.
General Description
A cell-permeable cis-enone resorlic acid lactone (RAL) and (5Z)-7-Oxozeaenol (Cat. No. 499610) analog that inhibits several kinases via an initial affinity binding to the ATP pocket, followed by a covalent adduct formation with a conserved ATP site cysteine residue of the targeted enzymes, including, but not limited to, Flt1/VEGFR-1, Flt3, cKit(D816V), MAPK1, MAPK2, MEK1, MKK6, PKCμ, PKD2, PRAK, and Tak1 (≥90% inhibition at 2 μM). Hypothemycin is also reported to inhibit two non-RAL targets (99% and 82% inhibition of TrkA and TrkB, respectively, at 2 μM), while one of the 46 putative cis-enone RALs targets, namely GSK-3α, is shown not to be affected. Hypothemycin inhibits multiple kinases involved in MAP kinase pathways and is therefore particularly effective in inhibiting BRAF(V600E)-dependent tumor growth. (5Z)-Zeaenol (Cat. No. 499609) may serve as a negative control.
Biochem/physiol Actions
Hypothemycin, one of the highly oxygenated analogues in the group of 14-membered resorcylic acid lactones (RAL), has minor antifungal and cytotoxic activity and exhibits an in vitro anti-malarial activity with an IC50 of 2.2 μg/mL. Hypothemycin is also reported to selectively and irreversibly inhibit protein kinases that contain a conserved cysteine residue (Cys166) that is located within the ATP-binding domain. Though this group accounts for less then 10% of all identified kinases, there are several targets implicated in aberrant cellular proliferation such as ERKs, MEK, FMS-like tyrosine kinase protein (FLT), and platelet-derived growth factor receptors (PDGFR). In cell culture, hypothemycin displays potent cytotoxicity against cancer cell lines that are dependent on certain activating kinase mutations. Additionally, hypothemycin demonstrates significant tumor growth inhibition in at least three separate murine xenograft models. Hypothemycin also inhibits the production of several cytokines such as IL2, IL6, IFNγ, and TNFα.
References
1) Zhou et al. (1999), Resorcylic acid lactones: naturally occurring potent and selective inhibitors of MEK; J. Antibiot., 52 1086 2) Schirmer et al. (2006), Targeted covalent inactivation of protein kinases by resorcylic acid lactone polyketides; Proc. Natl. Acad. Sci. USA, 103 4234 3) Fukazawa et al. (2010), The resorcylic acid lactone hypothemycin selectively inhibits the mitogen-activated protein kinase kinase-extracellular signal-regulated kinase pathway in cells; Biol. Pharm. Bull., 33 168 4) Park et al. (2015), Hypothemycin inhibits tumor necrosis factor-α production by tristetraprolin-dependent down-regulation of mRNA stability in lipopolysaccharide-stimulated macrophages; Int. Immunopharmacol., 29 863
HYPOTHEMYCIN Preparation Products And Raw materials
Raw materials
Preparation Products
HYPOTHEMYCIN Suppliers
| Supplier | Tel | Country | ProdList | Advantage | |
|---|---|---|---|---|---|
| TargetMol Chemicals Inc. | +1-781-999-5354 +1-00000000000 | marketing@targetmol.com | United States | 19892 | 58 |
| Aladdin Scientific | +1-+1(833)-552-7181 | sales@aladdinsci.com | United States | 52927 | 58 |
| Shanghai Tauto Biotech Co., Ltd. | 021-51320588 | tauto@tautobiotech.com | China | 3989 | 66 |
| AdooQ BioScience, LLC | +1 (866) 930-6790 | info@adooq.com | United States | 2784 | 58 |
| Sigma-Aldrich | 021-61415566 800-8193336 | orderCN@merckgroup.com | China | 51471 | 80 |
| Shanghai EFE Biological Technology Co., Ltd. | 021-65675885 18964387627 | info@efebio.com | China | 9707 | 58 |
| Lynnchem | 86-(0)29-85992781 17792393971 | info@lynnchem.com | China | 4587 | 58 |
| Novachemistry | 44-20819178-90 02081917890 | info@novachemistry.com | United Kingdom | 4381 | 58 |
| Shenzhen Regent Biochemical Technology Co., Ltd. | 0755-0755-85201366 18938635012 | sales@regentsciences.com | China | 9302 | 58 |
| Shanghai Hongye Biotechnology Co. Ltd | 400-9205774 | sales@glpbio.cn | China | 6870 | 58 |