hypothemycin

ID: ALA471474

PubChem CID: 9929643

Max Phase: Preclinical

Molecular Formula: C19H22O8

Molecular Weight: 378.38

Molecule Type: Small molecule

Names and Identifiers

Synonyms: Hypothemycin | HYPOTHEMYCIN|CHEBI:83275|(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|(1aR,8S,10Z,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|CHEMBL471474|SCHEMBL10187414|DTXSID301017784|BDBM50129131|AKOS027263555|DB07905|Q27097139|Hypothemycin, from Hypomyces trichothecoides, >=98% (HPLC)|(2R,4R,6S,7S,9Z,12S)-Show More⌵

Canonical SMILES:  COc1cc(O)c2c(c1)[C@H]1O[C@@H]1C[C@H](O)[C@H](O)C(=O)/C=C\C[C@H](C)OC2=O

Standard 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

Standard InChI Key:  SSNQAUBBJYCSMY-KNTMUCJRSA-N

Molfile:  

     RDKit          2D

 29 31  0  0  0  0  0  0  0  0999 V2000
    1.3521   -1.7845    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    0.7071   -1.2701    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.0621   -1.7845    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -0.7422   -1.9681    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.7422   -2.7931    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.5465   -1.7845    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.1916   -1.2701    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.5495   -0.5268    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.0651   -0.5268    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.7795   -0.9393    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.7795   -1.7643    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    2.4940   -0.5268    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.4940    0.2982    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.2085    0.7107    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    3.2085    1.5357    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.7795    0.7107    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.0651    0.2982    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.7071    1.0415    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.8301    1.8573    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    0.0621    1.5559    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.7422    1.7395    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.5465    1.5559    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.9045    2.2992    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -2.1916    1.0415    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.8366    1.5559    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -2.5495    0.2982    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.3538    0.4818    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -0.0126    2.5531    0.0000 H   0  0  0  0  0  0  0  0  0  0  0  0
    1.6959    1.1905    0.0000 H   0  0  0  0  0  0  0  0  0  0  0  0
  2  1  2  0
  2  3  1  0
  9  2  1  0
  4  3  1  0
  4  5  1  1
  6  4  1  0
  6  7  1  0
  7  8  2  0
  8 26  1  0
 10  9  2  0
  9 17  1  0
 10 11  1  0
 10 12  1  0
 13 12  2  0
 13 14  1  0
 16 13  1  0
 15 14  1  0
 17 16  2  0
 18 17  1  0
 18 19  1  0
 20 18  1  0
 20 19  1  0
 21 20  1  0
 22 21  1  0
 22 23  1  1
 24 22  1  0
 24 25  1  1
 26 24  1  0
 26 27  2  0
 20 28  1  6
 18 29  1  1
M  END

Alternative Forms

1. Parent:

   

   ALA471474

   HYPOTHEMYCIN

Molecule Features

Natural Product: Yes

Oral: No

Chemical Probe: No

Parenteral: No

Molecule Type: Small molecule

Topical: No

First In Class: No

Black Box: No

Chirality: No

Availability: No

Prodrug: No

Calculated Properties

Molecular Weight: 378.38

Molecular Weight (Monoisotopic): 378.1315

AlogP: 1.03

#Rotatable Bonds: 1

Polar Surface Area: 125.82

Molecular Species: NEUTRAL

HBA: 8

HBD: 3

#RO5 Violations: ┄

HBA (Lipinski): 8

HBD (Lipinski): 3

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: 9.47

CX Basic pKa: ┄

CX LogP: 1.63

CX LogD: 1.63

Aromatic Rings: 1

Heavy Atoms: 27

QED Weighted: 0.49

Np Likeness Score: 2.52

References

1. Wee JL, Sundermann K, Licari P, Galazzo J..  (2006)  Cytotoxic hypothemycin analogues from Hypomyces subiculosus.,  69  (10): [PMID:17067161] [10.1021/np060258o]

2. Ayers S, Graf TN, Adcock AF, Kroll DJ, Matthew S, Carcache de Blanco EJ, Shen Q, Swanson SM, Wani MC, Pearce CJ, Oberlies NH..  (2011)  Resorcylic acid lactones with cytotoxic and NF-κB inhibitory activities and their structure-activity relationships.,  74  (5): [PMID:21513293] [10.1021/np200062x]

3. Xu J, Chen A, Go ML, Nacro K, Liu B, Chai CL..  (2011)  Exploring aigialomycin d and its analogues as protein kinase inhibitors for cancer targets.,  2  (9): [PMID:24900361] [10.1021/ml200067t]

4. Fakhouri L, El-Elimat T, Hurst DP, Reggio PH, Pearce CJ, Oberlies NH, Croatt MP..  (2015)  Isolation, semisynthesis, covalent docking and transforming growth factor beta-activated kinase 1 (TAK1)-inhibitory activities of (5Z)-7-oxozeaenol analogues.,  23  (21): [PMID:26481152] [10.1016/j.bmc.2015.09.037]

5. Xu L, Wu P, Xue J, Molnar I, Wei X..  (2017)  Antifungal and Cytotoxic β-Resorcylic Acid Lactones from a Paecilomyces Species.,  80  (8): [PMID:28749671] [10.1021/acs.jnatprod.7b00066]

6. Bensinger D, Stubba D, Cremer A, Kohl V, Waßmer T, Stuckert J, Engemann V, Stegmaier K, Schmitz K, Schmidt B..  (2019)  Virtual Screening Identifies Irreversible FMS-like Tyrosine Kinase 3 Inhibitors with Activity toward Resistance-Conferring Mutations.,  62  (5): [PMID:30742435] [10.1021/acs.jmedchem.8b01714]

7. Ghazanfari D, Noori MS, Bergmeier SC, Hines JV, McCall KD, Goetz DJ..  (2021)  A novel GSK-3 inhibitor binds to GSK-3β via a reversible, time and Cys-199-dependent mechanism.,  40  [PMID:33991821] [10.1016/j.bmc.2021.116179]

8. Al Subeh ZY, Li T, Ustoyev A, Obike JC, West PM, Khin M, Burdette JE, Pearce CJ, Oberlies NH, Croatt MP..  (2022)  Semisynthesis of Hypothemycin Analogues Targeting the C8-C9 Diol.,  85  (8.0): [PMID:35834411] [10.1021/acs.jnatprod.2c00434]

9. Cockram PE, Smith TK..  (2018)  Active Natural Product Scaffolds against Trypanosomatid Parasites: A Review.,  81  (9): [PMID:30234295] [10.1021/acs.jnatprod.8b00159]

Source

Source(1):

• Scientific Literature