Natural Product: NPC470568

Natural Product IDNPC470568
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (-)-(1's)-6,1'-O,O-Dimethylaverantin
IUPAC Name 1,3,8-trihydroxy-6-methoxy-2-[(1S)-1-methoxyhexyl]anthracene-9,10-dione
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL2071287
PubChem CID 60199901
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0002448] Benzenoids
      • [CHEMONTID:0000018] Anthracenes
        • [CHEMONTID:0000151] Anthraquinones
          • [CHEMONTID:0001598] Hydroxyanthraquinones

The Chemical Classification was calculated by Classyfire, a software for chemical taxonomy calculation. Reference: DOI:10.1186/s13321-016-0174-y.

  Chemical Representations

Standard InCHIKey KXEYRABENKSUQJ-INIZCTEOSA-N
Standard InCHI InChI=1S/C22H24O7/c1-4-5-6-7-16(29-3)19-15(24)10-13-18(22(19)27)21(26)17-12(20(13)25)8-11(28-2)9-14(17)23/h8-10,16,23-24,27H,4-7H2,1-3H3/t16-/m0/s1
SMILES CCCCCC(C1=C(C=C2C(=C1O)C(=O)C3=C(C2=O)C=C(C=C3O)OC)O)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   400.15 Volume:   403.839
?
Van der Waals volume.
Dense:   0.991 LogP:   5.135
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.503
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -6.343
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   7.0 Rigid Bonds:   18.0
TPSA:   113.29
?
Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   3.0 Rings:   3.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.516 GASA:   1.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.22 Fsp3:   0.364
MCE-18:   63.0
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Rejected GSK Rule:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   1
Colloidal aggregators:   0.382 Fluc inhibitor:   0.024
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.169
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.735
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.276 Promiscuous compounds:   0.56

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.972 MDCK Permeability:   -4.772
Pgp-inhibitor:   0.339 Pgp-substrate:   0.076
PAMPA:   0.609
?
The experimental data for Peff was logarithmically transformed (logPeff). Molecules with log Peff values below 2.0 were classified as low-permeability (Category 0), while those with log Peff values exceeding 2.5 were classified as high-permeability (Category 1).
 Human Intestinal Absorption (HIA):   0.196
20% Bioavailability (F20%):   0.075 30% Bioavailability (F30%):   0.543
50% Bioavailability (F50%):   0.942

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.785
Plasma Protein Binding (PPB):   98.558% Volume Distribution (VD):   0.974
Fu: 1.322%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.874
OATP1B3 inhibitor:   0.995 BCRP inhibitor:   0.372
BSEP inhibitor:   0.473

ADMET: Metabolism

CYP1A2-inhibitor:   0.391 CYP1A2-substrate:   0.995
CYP2C19-inhibitor:   0.625 CYP2C19-substrate:   0.882
CYP2C9-inhibitor:   0.534 CYP2C9-substrate:   0.004
CYP2D6-inhibitor:   0.019 CYP2D6-substrate:   0.881
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.997
CYP2B6-substrate:   0.001 CYP2C8-inhibitor:   1.0
HLM stability:   0.915
?
Human liver microsomal (HLM) stability. Category 0: stable+ (HLM > 30 min); Category 1: unstable- (HLM ≤ 30 min). The output value is the probability of human liver microsomal instability, where a value closer to 1 indicates a higher likelihood of instability.

ADMET: Excretion

Clearance (CL):  2.713 Half-life (T1/2):  1.298

ADMET: Toxicity

hERG Blockers:  0.17 hERG Blockers (10um):  0.601
Human Hepatotoxicity (H-HT):  0.855 Drug-induced Liver Injury (DILI):  0.981
AMES Toxicity:  0.908 Rat Oral Acute Toxicity:  0.615
Maximum Recommended Daily Dose:  0.705 Skin Sensitization:  0.944
Carcinogencity:  0.677 Eye Corrosion:  0.0
Eye Irritation:  0.937 Respiratory Toxicity:  0.96
Drug-induced Neurotoxicity:  0.176 Ototoxicity:  0.698
Hematotoxicity:  0.84 Drug-induced Nephrotoxicity:  0.854
Genotoxicity:  0.515 RPMI-8226 Immunitoxicity:  0.522
A549 Cytotoxicity:  0.994 Hek293 Cytotoxicity:  0.764
BCF:   1.802
?
Bioconcentration factors are used for considering secondary poisoning potential and assessing risks to human health via the food chain. The unit is -log10[(mg/L)/(1000*MW)].
 IGC50:   4.658
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.094
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.56
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96 hour fathead minnow LC50. The unit of LC50FM is -log10[(mg/L)/(1000*MW)].

  Species Source

Organism ID Organism Name Taxonomy Level Family SuperKingdom Isolation Part Collection Location Collection Time Reference
NPO31572 Aspergillus sp. Species Aspergillaceae Eukaryota rhizosphere Sonoran desert n.a. PMID[15620238]
NPO31572 Aspergillus sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[17542490]
NPO31572 Aspergillus sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[17564467]
NPO31572 Aspergillus sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[19053517]
NPO31572 Aspergillus sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[21366228]
NPO31572 Aspergillus sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[21718031]
NPO31572 Aspergillus sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[21854017]
NPO31572 Aspergillus sp. Species Aspergillaceae Eukaryota healthy leaf of Ginkgo biloba campus of Nanjing University, Nanjing, China 2008-OCT PMID[22196792]
NPO31572 Aspergillus sp. Species Aspergillaceae Eukaryota isolated from the sponge Xestospongia testudinaria n.a. n.a. PMID[22225637]
NPO31572 Aspergillus sp. Species Aspergillaceae Eukaryota Isolated from a sandy-loam soil sample 50 m inland from Waikiki Beach, Honolulu, Hawaii 2010-JUL PMID[22400916]
NPO31572 Aspergillus sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[22703109]
NPO31572 Aspergillus sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[23527875]
NPO31572 Aspergillus sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[24050204]
NPO31572 Aspergillus sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[25001296]
NPO31572 Aspergillus sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[25581396]
NPO31572 Aspergillus sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[26273902]
NPO31572 Aspergillus sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[31012585]
NPO31572 Aspergillus sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[33305943]

Note for Reference:
In addition to directly collecting NP source organism data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated them from below databases:
☉ UNPD: Universal Natural Products Database [PMID: 23638153].
☉ StreptomeDB: a database of streptomycetes natural products [PMID: 33051671].
☉ TM-MC: a database of medicinal materials and chemical compounds in Northeast Asian traditional medicine [PMID: 26156871].
☉ TCM@Taiwan: a Traditional Chinese Medicine database [PMID: 21253603].
☉ TCMID: a Traditional Chinese Medicine database [PMID: 29106634].
☉ TCMSP: The traditional Chinese medicine systems pharmacology database and analysis platform [PMID: 24735618].
☉ HerDing: a herb recommendation system to treat diseases using genes and chemicals [PMID: 26980517].
☉ MetaboLights: a metabolomics database [PMID: 27010336].
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].



  NP Quantity Composition/Concentration

Organism ID Organism Name Organism Material Preparation Organism Part NP Quantity (Standard) NP Quantity (Minimum) NP Quantity (Maximum) Quantity Unit Reference

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP quantitative records for specific NP domains (e.g., NPS from foods or herbs) from domain-specific databases. These databases include:
☉ DUKE: Dr. Duke's Phytochemical and Ethnobotanical Databases.
☉ PHENOL EXPLORER: is the first comprehensive database on polyphenol content in foods [PMID: 24103452], its homepage can be accessed at here.
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].



 Biological Activity

Molecular-level activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT395 Cell line SF-268 Homo sapiens IC50 > 50000.0 nM PMID[26316467]
NPT83 Cell line MCF7 Homo sapiens IC50 > 50000.0 nM PMID[18824363]
NPT397 Cell line NCI-H460 Homo sapiens IC50 > 50000.0 nM PMID[26636180]

In vivo activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference





 Experimental ADME

Experiment Model Experiment Tissue ADME Type ADME Relation ADME Value ADME Unit Reference





 Experimental Toxicity

Quantitative toxicity

Experiment Model Experiment Organism Toxicity Type Toxicity Relation Toxicity Value Toxicity Unit Reference

Common Abbreviations:
LC: Lethal Concentration; LD: Lethal Dose; LT:Lethal Time; NOAEL: No-observed-adverse-effect Level; BMDL: Benchmark Dose Lower Confidence Limit; BMD: Benchmark Dose; BMC:Benchmark Concentration; LOAEL: Lowest Observed Adverse Effect Level; RfD:Reference Dose; RfC:Reference Concentration; MRL: Minimal Risk Level; MEG: Maximum Exposure Guideline; PAC: Protective Action Criteria

Categorical toxicity labels

Hepatotoxicity Carcinogenicity Mutagenicity Cardiotoxicity Respiratory Toxicity Eye Irritation Endocrine Disruption
Hepatotoxicity Carcinogenicity Mutagenicity Cardiotoxicity Respiratory Toxicity Eye Irritation Endocrine Disruption

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP toxicity records from domain-specific databases. These databases include:
☉ ToxValDB: a curated database that compiles quantitative toxicity values for chemicals from diverse public sources to support toxicological research and risk assessment.
☉ TOXRIC: a comprehensive, free-to-access, online database providing toxicological/feature data. The toxicity labels are retrieved from this database. [PMID: 36400569]


  Chemically structural similarity

Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes approximately 50,000 NPs with experimentally-derived bioactivity available in NPASS)

Similarity is measured using the Tanimoto coefficient (Tc) , which compares the binary fingerprints of two molecules. Tc is calculated as the intersection divided by the union of '1' bits in the fingerprints, ranging from 0 to 1, with 1 indicating highest similarity.

●  The left chart: Distribution of similarity level between NPC470568 and all remaining natural products in the NPASS database.
●  The right table: Most similar natural products (Tc>=0.5 or Top200).

Similarity Score Similarity Level Natural Product ID
0.7193 Intermediate Similarity NPC470566
0.7193 Intermediate Similarity NPC470562
0.7115 Intermediate Similarity NPC34482
0.6316 Remote Similarity NPC470561
0.614 Remote Similarity NPC470569
0.5763 Remote Similarity NPC470570
0.5577 Remote Similarity NPC19896
0.537 Remote Similarity NPC126767
0.5185 Remote Similarity NPC312929
0.5156 Remote Similarity NPC470563
0.5091 Remote Similarity NPC107109
0.5091 Remote Similarity NPC294646

Similar Clinical/Approved Drugs

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules.

●  The left chart: Distribution of similarity level between NPC470568 and all drugs/candidates.
●  The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

Similarity Score Similarity Level Drug ID Developmental Stage
NPD

Bioactivity similarity

  Bioactivity similarity

Similar Natural Products in NPASS

Similarity level is defined by Bioactivity similarity was calculated based on bioactivity descriptors of compounds. The bioactivity descriptors were calculated by a recently developed AI algorithm Chemical Checker (CC) [Nature Biotechnology, 38:1087–1096, 2020; Nature Communications, 12:3932, 2021], which evaluated bioactivity similarities at five levels:
☉ A: chemistry similarity;
☉ B: biological targets similarity;
☉ C: networks similarity;
☉ D: cell-based bioactivity similarity;
☉ E: similarity based on clinical data.
Those 5 categories of CC bioactivity descriptors were calculated and then subjected to manifold projection using UMAP algorithm, to project all NPs on a 2-Dimensional space. The current NP was highlighted with a small circle in the 2-D map. Below figures: left-to-right, A-to-E.

A: chemistry similarity
B: biological targets similarity
C: networks similarity
D: cell-based bioactivity similarity
E: similarity based on clinical data