Natural Product (NP) Details

General Information of the NP (ID: NP4592)
Name
Mithramycin A
Synonyms
NCGC00181319-05; NCGC00181319-01; DSSTox_CID_3492; DSSTox_RID_77052; Plicatomycin; DSSTox_GSID_23492; CAS-18378-89-7; AC1NR4RB; SCHEMBL4516; DTXSID6023492; Tox21_112787; Tox21_112751; NCGC00181319-08; NCGC00181319-06; NCGC00181319-03; NCGC00181319-04; NCGC00181319-02; NCGC00181319-07
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Species Origin Streptomyces tanashiensis ...     Click to Show/Hide
Streptomyces tanashiensis
SuperKingdom: Bacteria
Phylum: Actinobacteria
Class: Actinomycetia
Order: Streptomycetales
Family: Streptomycetaceae
Genus: Streptomyces
Species: Streptomyces tanashiensis
Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z] Withdrawn from market [1]
Structure
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2D MOL

3D MOL

ADMET Property
Absporption
Caco-2 Permeability
 -6.196
 
MDCK Permeability
 -5.145
 
PAMPA
 +++
 
HIA
 - - -
 
Distribution
VDss
 0.074
 
PPB
 84.2%
 
BBB
 - - -
 
Metabolism
CYP1A2 inhibitor
 - - -
CYP1A2 substrate
 - - -
CYP2C19 inhibitor
 - - -
CYP2C19 substrate
 - - -
CYP2C9 inhibitor
 - - -
CYP2C9 substrate
 - - -
CYP2D6 inhibitor
 - - -
CYP2D6 substrate
 - - -
CYP3A4 inhibitor
 - - -
CYP3A4 substrate
 +
CYP2B6 inhibitor
 +++
CYP2B6 substrate
 - - -
CYP2C8 inhibitor
 +++
HLM Stability
 +++
 
Excretion
CLplasma
 -0.517
 
T1/2
 9.082
Toxicity
DILI
 +++
 
Rat Oral Acute Toxicity
 - -
 
FDAMDD
 -
 
Respiratory
 - - -
 
Human Hepatotoxicity
 +
 
Ototoxicity
 +++
 
Drug-induced Nephrotoxicity
 +++
 
Drug-induced Neurotoxicity
 - - -
 
Hematotoxicity
 - - -
 
Genotoxicity
 +++
 
Tips: 1. For the classification endpoints, the prediction probability values are transformed into six symbols: 0-0.1 (- - -), 0.1-0.3 (- -), 0.3-0.5 (-), 0.5-0.7 (+), 0.7-0.9 (++), and 0.9-1.0 (+++). 2. Additionally, the corresponding relationships of the three labels are as follows: excellent; medium; poor.
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Formula
C52H76O24
PubChem CID
163659
Canonical SMILES
CC1C(C(CC(O1)OC2CC(OC(C2O)C)OC3=CC4=CC5=C(C(=O)C(C(C5)C(C(=O)C(C(C)O)O)OC)OC6CC(C(C(O6)C)O)OC7CC(C(C(O7)C)O)OC8CC(C(C(O8)C)O)(C)O)C(=C4C(=C3C)O)O)O)O
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
InChIKey
CFCUWKMKBJTWLW-BKHRDMLASA-N
CAS Number
CAS 18378-89-7
ChEBI ID
CHEBI:31856
TTD Drug ID
D0GU4Q
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Drug(s) Whose Efficacy can be Enhanced by This NP
          Vorinostat      Mycosis fungoides     Click to Show/Hide the Molecular Data of This Drug
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [2]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    In-vitro Model Primary tumor cells derived from Sezary syndrome patients Sezary syndrome Homo sapiens
                    Experimental
                    Result(s)		 MTR, like SAHA, induced the apoptosis of SS cells, while the two drugs in combination showed clear synergy or potentiation.
Target and Pathway
Target(s) RNA-binding musashi-2 (MSI2)  Molecule Info  [3]
References
Reference 1 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 8394).
Reference 2 Vorinostat and Mithramycin A in combination therapy as an interesting strategy for the treatment of Sezary T lymphoma: a transcriptomic approach. Arch Dermatol Res. 2017 Oct;309(8):611-623.
Reference 3 The Pluripotency Factor Musashi-2 Is a Novel Target for Lung Cancer Therapy.Ann Am Thorac Soc. 2018 Apr;15(Supplement_2):S124.
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