Natural Product (NP) Details

General Information of the NP (ID: NP4339)
Name
Aclarubicin
Synonyms
aclarubicin; Aclacinomycin A; 57576-44-0; Aclarubicine; Aclarubicinum; NSC-208734; UNII-74KXF8I502; MA 144-A1; Aclucinomycin A; 74KXF8I502; Aclacinon; Aclacur; Jaclacin; methyl (1R,2R,4S)-4-[(2R,4S,5S,6S)-4-(dimethylamino)-5-[(2S,4S,5S,6S)-4-hydroxy-6-methyl-5-[(2R,6S)-6-methyl-5-oxooxan-2-yl]oxyoxan-2-yl]oxy-6-methyloxan-2-yl]oxy-2-ethyl-2,5,7-trihydroxy-6,11-dioxo-3,4-dihydro-1H-tetracene-1-carboxylate; Aclarubicino; Aclarubicins; Aclacin; CHEBI:77980; ACLACINOMYCIN A1; methyl (1R,2R,4S)-2-ethyl-2,5,7-trihydroxy-6,11-dioxo-4-{[2,3,6-trideoxy-4-O-{2,6-dideoxy-4-O-[(2R,6S)-6-methyl-5-oxotetrahydro-2H-pyran-2-yl]-alpha-L-lyxo-hexopyranosyl}-3-(dimethylamino)-alpha-L-lyxo-hexopyranosyl]oxy}-1,2,3,4,6,11-hexahydrotetracene-1-carboxylate; Antibiotic MA 144A; Aclarubicine [INN-French]; Aclarubicinum [INN-Latin]; Aclarubicino [INN-Spanish]; aclarubicina; Aclarubicin [USAN:INN:BAN]; CCRIS 2262; EINECS 260-824-3; Spectrum_000467; Spectrum2_001934; Spectrum4_000768; Spectrum5_001041; Aclarubicin (USAN/INN); SCHEMBL4532; KBioGR_001156; KBioSS_000947; SPBio_001967; CHEMBL502620; DTXSID1022554; CHEBI:74619; KBio2_000947; KBio2_003515; KBio2_006083; HMS2089B13; AW8655; BDBM50368351; CCG-39864; MFCD00866250; ZINC85537142; DB11617; 1-Naphthacenecarboxylic acid,(2-ethyl-1,2,3,4,6,11-hexahydro-2,5,7-trihydroxy-6,11-dioxo-4-((2,3,6-trideoxy-4-O-(2,6-dideoxy-4-O-((2R-trans)-tetrahydro-6-methyl-5-oxo-2H-pyran-2-yl)-alpha-L-lyxo-hexopyranosyl)-3-(dimethylamino)-alpha-L-lyxo-hexopyranosyl)-3-(dimethylamino)-alpha-L-Lyxo-hexopyranosyl)oxy)-, methyl ester, (1R-(1alpha,2beta,4beta))-; Methyl (1R,2R,4S)-2-ethyl-1,2,3,4,6,11-hexahydro-2,5,7-trihydroxy-6,11-dioxo-4-((2,3,6-trideoxy-4-O-(2,6-dideoxy-4-O-((2R,6S)-tetrahydro-6-methyl-5-oxo-2H-pyran-2-yl)-alpha-L-lyxo-hexopyranosyl)-3-(dimethylamino)-alpha-L-lyxo-hexopyranosyl)oxy)-1-naphthacenecarboxylate; C18638; D02756; AB00052311-02; 576A440; Q4674302; 1-Naphthacenecarboxylic acid, 2-ethyl-1,2,3,4,6,11-hexahydro-2,5,7-trihydroxy-6,11-dioxo-4-((2,3,6-trideoxy-4-O-(2,6-dideoxy-4-O-((2R-trans)-tetrahydro-6-methyl-5-oxo-2H-pyran-2-yl)-alpha-L-lyxo-hexopyranosyl)-3-(dimethylamino)-alpha-L-lyxo-hexopyranosyl)oxy)-, methyl ester, (1R-(1alpha,2beta,4beta))-; 2-Ethyl-1,2,3,4,6,11-hexahydro-2,5,7-trihydroxy-6,11-dioxo-4-[[2,3,6-trideoxy-4-O-[2,6-dideoxy-4-O-[(2R-trans)-tetrahydro-6-methyl-5-oxo-2H-pyran-2-yl]-.alpha.-L-lyxo-hexopyranosyl]-3-(dimethylamino)-.alpha.-L-lyxo-hexopyranosyl]-oxy]-1-naphthacenecarboxalic acid methyl ester; methyl (1R,2R,4S)-4-[(2R,4S,5S,6S)-4-(dimethylamino)-5-[(2S,4S,5S,6S)-4-hydroxy-6-methyl-5-[(2R,6S)-6-methyl-5-oxo-tetrahydropyran-2-yl]oxy-tetrahydropyran-2-yl]oxy-6-methyl-tetrahydropyran-2-yl]oxy-2-ethyl-2,5,7-trihydroxy-6,11-dioxo-3,4-dihydro-1H-tetracene-1-carboxylate
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Species Origin Streptomyces galilaeus ...     Click to Show/Hide
Streptomyces galilaeus
SuperKingdom: Bacteria
Phylum: Actinobacteria
Class: Actinomycetia
Order: Streptomycetales
Family: Streptomycetaceae
Genus: Streptomyces
Species: Streptomyces galilaeus
Disease Acute myeloid leukemia [ICD-11: 2A60] Approved [1]
Structure
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2D MOL

3D MOL

ADMET Property
Absporption
Caco-2 Permeability
 -6.252
 
MDCK Permeability
 -4.977
 
PAMPA
 +++
 
HIA
 - - -
 
Distribution
VDss
 0.19
 
PPB
 83.6%
 
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
 4.913
 
T1/2
 4.465
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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    Click to Show/Hide the Molecular Information and External Link(s) of This Natural Product
Formula
C42H53NO15
PubChem CID
451415
Canonical SMILES
CCC1(CC(C2=C(C3=C(C=C2C1C(=O)OC)C(=O)C4=C(C3=O)C(=CC=C4)O)O)OC5CC(C(C(O5)C)OC6CC(C(C(O6)C)OC7CCC(=O)C(O7)C)O)N(C)C)O
InChI
1S/C42H53NO15/c1-8-42(51)17-28(33-22(35(42)41(50)52-7)14-23-34(38(33)49)37(48)32-21(36(23)47)10-9-11-26(32)45)56-30-15-24(43(5)6)39(19(3)54-30)58-31-16-27(46)40(20(4)55-31)57-29-13-12-25(44)18(2)53-29/h9-11,14,18-20,24,27-31,35,39-40,45-46,49,51H,8,12-13,15-17H2,1-7H3/t18-,19-,20-,24-,27-,28-,29-,30-,31-,35-,39+,40+,42+/m0/s1
InChIKey
USZYSDMBJDPRIF-SVEJIMAYSA-N
CAS Number
CAS 57576-44-0
ChEBI ID
CHEBI:77980
TTD Drug ID
D01UBX
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Drug(s) Whose Efficacy can be Enhanced by This NP
          Cytarabine + GC-SF     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
                    Experimental
                    Result(s)		 Increasing the dose of aclarubicin in CAG regimen seemed to be useful and relatively safe in relapsed and refractory AML.
Target and Pathway
Target(s) DNA topoisomerase II (TOP2)  Molecule Info  [3]
References
Reference 1 Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
Reference 2 Increasing the dose of aclarubicin in low-dose cytarabine and aclarubicin in combination with granulocyte colony-stimulating factor (CAG regimen) can safely and effectively treat relapsed or refractory acute myeloid leukemia. Int J Hematol. 2014;99(5):603-8.
Reference 3 Linker length in podophyllotoxin-acridine conjugates determines potency in vivo and in vitro as well as specificity against MDR cell lines. Anticancer Drug Des. 2001 Dec;16(6):305-15.
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