Natural Product: NPC66593

Natural Product IDNPC66593
Common Name
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The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Aloesaponarin I
IUPAC Name methyl 3,8-dihydroxy-1-methyl-9,10-dioxoanthracene-2-carboxylate
Synonyms Aloesaponarin I
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL470819
PubChem CID 11098986
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0002448] Benzenoids
      • [CHEMONTID:0000018] Anthracenes
        • [CHEMONTID:0001911] Anthracenecarboxylic acids and derivatives
          • [CHEMONTID:0002424] Anthracenecarboxylic acids

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 OWMIPWWYWUGBCG-UHFFFAOYSA-N
Standard InCHI InChI=1S/C17H12O6/c1-7-12-9(6-11(19)13(7)17(22)23-2)15(20)8-4-3-5-10(18)14(8)16(12)21/h3-6,18-19H,1-2H3
SMILES COC(=O)c1c(O)cc2c(c1C)C(=O)c1c(C2=O)cccc1O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   312.06 Volume:   305.932
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Van der Waals volume.
Dense:   1.02 LogP:   4.201
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.415
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -6.68
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The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   19.0
TPSA:   100.9
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Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   2.0 Rings:   3.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.666 GASA:   1.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.422 Fsp3:   0.118
MCE-18:   40.0
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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:   0.259 Fluc inhibitor:   0.17
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.318
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.666
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.425 Promiscuous compounds:   0.353

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.2 MDCK Permeability:   -4.786
Pgp-inhibitor:   0.687 Pgp-substrate:   0.099
PAMPA:   0.763
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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):   0.229
20% Bioavailability (F20%):   0.036 30% Bioavailability (F30%):   0.775
50% Bioavailability (F50%):   0.961

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.002 MRP1:   0.942
Plasma Protein Binding (PPB):   96.568% Volume Distribution (VD):   -0.079
Fu: 3.087%
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The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.95
OATP1B3 inhibitor:   0.997 BCRP inhibitor:   0.422
BSEP inhibitor:   0.555

ADMET: Metabolism

CYP1A2-inhibitor:   0.76 CYP1A2-substrate:   0.726
CYP2C19-inhibitor:   0.191 CYP2C19-substrate:   0.561
CYP2C9-inhibitor:   0.102 CYP2C9-substrate:   0.187
CYP2D6-inhibitor:   0.015 CYP2D6-substrate:   0.741
CYP3A4-inhibitor:   0.147 CYP3A4-substrate:   0.64
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.994
HLM stability:   0.66
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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):  2.483 Half-life (T1/2):  1.256

ADMET: Toxicity

hERG Blockers:  0.046 hERG Blockers (10um):  0.538
Human Hepatotoxicity (H-HT):  0.591 Drug-induced Liver Injury (DILI):  0.989
AMES Toxicity:  0.904 Rat Oral Acute Toxicity:  0.469
Maximum Recommended Daily Dose:  0.388 Skin Sensitization:  0.967
Carcinogencity:  0.85 Eye Corrosion:  0.0
Eye Irritation:  0.958 Respiratory Toxicity:  0.872
Drug-induced Neurotoxicity:  0.273 Ototoxicity:  0.527
Hematotoxicity:  0.627 Drug-induced Nephrotoxicity:  0.615
Genotoxicity:  0.61 RPMI-8226 Immunitoxicity:  0.354
A549 Cytotoxicity:  0.871 Hek293 Cytotoxicity:  0.603
BCF:   1.834
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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:   4.354
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.333
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.813
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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
NPO1248 Scutia myrtina Species Rhamnaceae Eukaryota roots n.a. n.a. PMID[17378532]
NPO1248 Scutia myrtina Species Rhamnaceae Eukaryota n.a. bark n.a. PMID[19282186]
NPO1248 Scutia myrtina Species Rhamnaceae Eukaryota n.a. Madagascar forest n.a. PMID[19282186]
NPO1248 Scutia myrtina Species Rhamnaceae Eukaryota n.a. n.a. n.a. Database[UNPD]

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
NPT179 Cell line A2780 Homo sapiens IC50 > 32000.0 nM PubChem BioAssay data set
NPT6 Organism Plasmodium falciparum Plasmodium falciparum IC50 = 5580.0 nM PMID[20800321]
NPT6 Organism Plasmodium falciparum Plasmodium falciparum IC50 = 77600.0 nM Open TG-GATES in vivo data: Biochemistry
NPT2 Others Unspecified n.a. Ratio IC50 > 5.7 n.a. Open TG-GATES in vivo data: Biochemistry

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 NPC66593 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
0.6842 Remote Similarity NPC318270
0.619 Remote Similarity NPC317580
0.6 Remote Similarity NPC326084
0.5821 Remote Similarity NPC475449
0.58 Remote Similarity NPC604901
0.549 Remote Similarity NPC21599
0.5476 Remote Similarity NPC103540
0.5238 Remote Similarity NPC375356
0.5227 Remote Similarity NPC300274
0.5106 Remote Similarity NPC604340
0.5102 Remote Similarity NPC282923
0.5091 Remote Similarity NPC610494

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC66593 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
0.5476 Remote Similarity NPD1470 Phase 4

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