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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
Last updated:2023-06-08 09:02:11

HYPOTHEMYCIN Properties

Melting point 170-172℃
storage temp. -20°C
solubility DMSO: soluble
form Lyophilized solid
color White
Stability Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 3 months.

SAFETY

Risk and Safety Statements

Symbol(GHS)  GHS hazard pictograms
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
0
2 0

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
Product number Packaging Price Buy
H1667 250μg $221 Buy
H1667 1mg $679 Buy
27913 1mg $199 Buy
H998480 5mg $1620 Buy
207223 250ug $342 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

Global( 28)Suppliers
Supplier Tel Email 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 9715 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 9303 58
Shanghai Hongye Biotechnology Co. Ltd 400-9205774 sales@glpbio.cn China 6870 58
HYPOTHEMYCIN (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 (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 Hypothemicin Nsc354462 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)- (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 f 152 D2 Hypothemycin - CAS 76958-67-3 - Calbiochem 76958-67-3 Antibiotic