1-(4,9-dihydroxy-12-(2-((4-hydroxyphenoxy)carbonyloxy)propyl)-2,6,7,11-tetramethoxy-3,10-dioxo-3,10-dihydroperylen-1-yl)propan-2-yl benzoate

ID: ALA460433

Max Phase: Preclinical

Molecular Formula: C44H38O14

Molecular Weight: 790.77

Molecule Type: Small molecule

Names and Identifiers

Synonyms: Calphostin C

Canonical SMILES:  COc1c(C[C@@H](C)OC(=O)Oc2ccc(O)cc2)c2c3c(C[C@@H](C)OC(=O)c4ccccc4)c(OC)c(=O)c4c(O)cc(OC)c(c5c(OC)cc(O)c(c1=O)c52)c43

Standard InChI:  InChI=1S/C44H38O14/c1-20(56-43(50)22-10-8-7-9-11-22)16-25-31-32-26(17-21(2)57-44(51)58-24-14-12-23(45)13-15-24)42(55-6)40(49)34-28(47)19-30(53-4)36(38(32)34)35-29(52-3)18-27(46)33(37(31)35)39(48)41(25)54-5/h7-15,18-21,45-47H,16-17H2,1-6H3/t20-,21-/m1/s1

Standard InChI Key:  SRJYZPCBWDVSGO-NHCUHLMSSA-N

Molfile:  

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M  END

Alternative Forms

1. Parent:

   

   ALA460433

   CALPHOSTIN C

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: 790.77

Molecular Weight (Monoisotopic): 790.2262

AlogP: 6.98

#Rotatable Bonds: 12

Polar Surface Area: 193.58

Molecular Species: ACID

HBA: 14

HBD: 3

#RO5 Violations: 3

HBA (Lipinski): 14

HBD (Lipinski): 3

#RO5 Violations (Lipinski): 3

CX Acidic pKa: 6.47

CX Basic pKa: 3.19

CX LogP: 8.31

CX LogD: 6.89

Aromatic Rings: 7

Heavy Atoms: 58

QED Weighted: 0.05

Np Likeness Score: 0.66

References

1. Itoh T, Ohguchi K, Iinuma M, Nozawa Y, Akao Y..  (2008)  Inhibitory effect of xanthones isolated from the pericarp of Garcinia mangostana L. on rat basophilic leukemia RBL-2H3 cell degranulation.,  16  (8): [PMID:18328716] [10.1016/j.bmc.2008.02.054]

2. Xie HZ, Li LL, Ren JX, Zou J, Yang L, Wei YQ, Yang SY..  (2009)  Pharmacophore modeling study based on known spleen tyrosine kinase inhibitors together with virtual screening for identifying novel inhibitors.,  19  (7): [PMID:19254842] [10.1016/j.bmcl.2009.02.049]

3. Lee SB, Park YI, Dong MS, Gong YD..  (2010)  Identification of 2,3,6-trisubstituted quinoxaline derivatives as a Wnt2/β-catenin pathway inhibitor in non-small-cell lung cancer cell lines.,  20  (19): [PMID:20729080] [10.1016/j.bmcl.2010.07.088]

4. PubChem BioAssay data set, 

5. Gong YD, Dong MS, Lee SB, Kim N, Bae MS, Kang NS..  (2011)  A novel 3-arylethynyl-substituted pyrido[2,3,-b]pyrazine derivatives and pharmacophore model as Wnt2/β-catenin pathway inhibitors in non-small-cell lung cancer cell lines.,  19  (18): [PMID:21855350] [10.1016/j.bmc.2011.07.028]

6. Zhang M, Catrow JL, Ji H..  (2013)  High-Throughput Selectivity Assays for Small-Molecule Inhibitors of β-Catenin/T-Cell Factor Protein-Protein Interactions.,  4  (2): [PMID:24900664] [10.1021/ml300367f]

7. Hahne G, Grossmann TN..  (2013)  Direct targeting of β-catenin: Inhibition of protein-protein interactions for the inactivation of Wnt signaling.,  21  (14): [PMID:23566764] [10.1016/j.bmc.2013.02.050]

8. Zeller J, Turbiak AJ, Powelson IA, Lee S, Sun D, Showalter HD, Fearon ER..  (2013)  Investigation of 3-aryl-pyrimido[5,4-e][1,2,4]triazine-5,7-diones as small molecule antagonists of β-catenin/TCF transcription.,  23  (21): [PMID:24060489] [10.1016/j.bmcl.2013.08.111]

9. Catrow JL, Zhang Y, Zhang M, Ji H..  (2015)  Discovery of Selective Small-Molecule Inhibitors for the β-Catenin/T-Cell Factor Protein-Protein Interaction through the Optimization of the Acyl Hydrazone Moiety.,  58  (11): [PMID:25985283] [10.1021/acs.jmedchem.5b00223]

10.  (2016)  Substituted 1H-indazol-1-ol analogs as inhibitors of beta catenin/Tcf protein-protein interactions, 

11. Phull MS, Jadav SS, Gundla R, Mainkar PS..  (2021)  A perspective on medicinal chemistry approaches towards adenomatous polyposis coli and Wnt signal based colorectal cancer inhibitors.,  212  [PMID:33445154] [10.1016/j.ejmech.2020.113149]

Source

Source(3):

• Scientific Literature
• PubChem BioAssays
• BindingDB Database