mithramycin   Click here for help

GtoPdb Ligand ID: 8394

Synonyms: aureolic acid | Mithracin® | mithramycin A | MMA
Approved drug PDB Ligand
mithramycin is an approved drug (FDA (1970))
Compound class: Natural product
Comment: We show one representation of mithramycin here. As a natural product there are alternate chemical structures due to the complex stereochemistry. Also known as plicamycin, the compound has been used clinically as an antineoplastic antibacterial (produced by Streptomyces plicatus).

mithramycin is commercially available from our sponsors

2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 21
Hydrogen bond donors 11
Rotatable bonds 15
Topological polar surface area 358.2
Molecular weight 1084.47
XLogP -0.39
No. Lipinski's rules broken 3

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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Canonical SMILES COC(C1Cc2cc3cc(OC4OC(C)C(C(C4)OC4CC(O)C(C(O4)C)O)O)c(c(c3c(c2C(=O)C1OC1OC(C)C(C(C1)OC1OC(C)C(C(C1)OC1OC(C)C(C(C1)(C)O)O)O)O)O)O)C)C(=O)C(C(O)C)O
Isomeric SMILES CO[C@@H]([C@@H]1Cc2cc3cc(O[C@@H]4O[C@H](C)[C@H]([C@@H](C4)O[C@H]4C[C@@H](O)[C@@H]([C@H](O4)C)O)O)c(c(c3c(c2C(=O)[C@H]1O[C@@H]1O[C@H](C)[C@H]([C@@H](C1)O[C@@H]1O[C@H](C)[C@@H]([C@@H](C1)O[C@@H]1O[C@H](C)[C@H]([C@@](C1)(C)O)O)O)O)O)O)C)C(=O)[C@H]([C@H](O)C)O
InChI InChI=1S/C52H76O24/c1-18-29(72-34-14-30(43(58)21(4)68-34)73-33-13-28(54)42(57)20(3)67-33)12-26-10-25-11-27(49(66-9)48(63)41(56)19(2)53)50(47(62)39(25)46(61)38(26)40(18)55)76-36-16-31(44(59)23(6)70-36)74-35-15-32(45(60)22(5)69-35)75-37-17-52(8,65)51(64)24(7)71-37/h10,12,19-24,27-28,30-37,41-45,49-51,53-61,64-65H,11,13-17H2,1-9H3/t19-,20-,21-,22-,23-,24-,27+,28-,30-,31-,32-,33+,34+,35+,36+,37+,41+,42-,43-,44-,45+,49+,50+,51-,52+/m1/s1
InChI Key CFCUWKMKBJTWLW-BKHRDMLASA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
No information available.
Summary of Clinical Use Click here for help
Before withdrawl from the market, this compound was used in the treatment of testicular cancer [1], Paget’s disease of bone, hypercalcemia and hypercalciuria.
Mechanism Of Action and Pharmacodynamic Effects Click here for help
Mithramycin binds to DNA and prevents association of transcriptional activators at GC-rich binding sites [2]. Mithramycin inhibits histone methyltransferase (HMT) enzyme activity in lung cancer cells [3], and is effective against SETDB1 HMT protein overexpression which drives tumorigenesis in non-small and small lung cancer cell lines and primary tumours [4]. The drug is also effective in inhibiting aberrant HMT-induced histone H3 (K9) trimethylation in Huntington's disease (HD) and may therefore present a novel neuroprotective mechanism for treating HD [5].