(2R,4R,6S,7S,12S)-6,7,16-trihydroxy-18-methoxy-12-methyl-3,13-dioxatricyclo[13.4.0.02,4]nonadeca-1(19),9,15,17-tetraene-8,14-dione

• ChemBase ID: 5536
• Molecular Formular: C19H22O8
• Molecular Mass: 378.37318
• Monoisotopic Mass: 378.13146766
• SMILES: O=C1O[C@@H](C)C/C=C\C(=O)[C@H]([C@H](C[C@@H]2[C@@H](c3c1c(O)cc(OC)c3)O2)O)O
• Canonical SMILES: COc1cc2[C@H]3O[C@@H]3C[C@H](O)[C@H](O)C(=O)/C=C\C[C@@H](OC(=O)c2c(c1)O)C
• InChI: InChI=1S/C19H22O8/c1-9-4-3-5-12(20)17(23)14(22)8-15-18(27-15)11-6-10(25-2)7-13(21)16(11)19(24)26-9/h3,5-7,9,14-15,17-18,21-23H,4,8H2,1-2H3/b5-3-/t9-,14-,15+,17+,18+/m0/s1
• InChIKey: SSNQAUBBJYCSMY-KNTMUCJRSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: (2R,4R,6S,7S,12S)-6,7,16-trihydroxy-18-methoxy-12-methyl-3,13-dioxatricyclo[13.4.0.0^2,^4]nonadeca-1(19),9,15,17-tetraene-8,14-dione; (2R,4R,6S,7S,9Z,12S)-6,7,16-trihydroxy-18-methoxy-12-methyl-3,13-dioxatricyclo[13.4.0.0^{2,4}]nonadeca-1(19),9,15,17-tetraene-8,14-dione
• IUPAC Traditional name: (2R,4R,6S,7S,12S)-6,7,16-trihydroxy-18-methoxy-12-methyl-3,13-dioxatricyclo[13.4.0.0^2,^4]nonadeca-1(19),9,15,17-tetraene-8,14-dione; (2R,4R,6S,7S,9Z,12S)-6,7,16-trihydroxy-18-methoxy-12-methyl-3,13-dioxatricyclo[13.4.0.0^{2,4}]nonadeca-1(19),9,15,17-tetraene-8,14-dione
• Synonyms: 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)-; NSC354462; Hypothemycin; (1aR,8S,13S,14S,15aR)-5,13,14-trihydroxy-3-methoxy-8-methyl-8,9,13,14,15,15a-hexahydro-6H-oxireno[k][2]benzoxacyclotetradecine-6,12(1aH)-dione

Database IDs

• CAS Number: 76958-67-3
• MDL Number: MFCD08457932
• PubChem SID: 160968964; 99444376
• PubChem CID: 9929643

CALCULATED PROPERTIES

JChem

• Acid pKa: 9.474741
• H Acceptors: 7
• H Donor: 3
• LogD (pH = 5.5): 1.6342845
• LogD (pH = 7.4): 1.6307199
• Log P: 1.6343302
• Molar Refractivity: 94.9755 cm^3
• Polarizability: 36.720337 Å^3
• Polar Surface Area: 125.82 Å^2
• Rotatable Bonds: 1
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 0.95
• LOG S: -2.31
• Solubility (Water): 1.86e+00 g/l

PROPERTIES

Physical Property

• Solubility: acetone: soluble; deionized water: insoluble; DMSO: soluble

Safety Information

• European Hazard Symbols: Harmful (Xn)
• German water hazard class: 3
• Risk Statements: 22
• GHS Pictograms: GHS07
• GHS Signal Word: Warning
• GHS Hazard statements: H302
• Storage Temperature: -20°C

Product Information

• Purity: ≥98% (HPLC)
• Biological Source: from Hypomyces trichothecoides
• Empirical Formula (Hill Notation): C19H22O8

DETAILS

DrugBank - DB07905

Drug information: experimental

Sigma Aldrich - H1667

Biochem/physiol Actions
Hypothemycin, one of the highly oxygenated analogues in the group of 14-membered resorcylic acid lactones (RAL),1,2,3 has minor antifungal and cytotoxic activity and exhibits an in vitro anti-malarial activity with an IC50 of 2.2 μg/mL.4 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.1,2,3,5 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).1 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.1,5 Hypothemycin also inhibits the production of several cytokines such as IL2, IL6, IFNγ, and TNFα.5