Natural Product: NPC132990

Natural Product IDNPC132990
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Altersolanol B
IUPAC Name (2R,3S)-2,3,8-trihydroxy-6-methoxy-3-methyl-2,4-dihydro-1H-anthracene-9,10-dione
Synonyms Altersolanol B
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL2011669
PubChem CID 161389
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 AAHQQIFXAQHGBD-WBMJQRKESA-N
Standard InCHI InChI=1S/C16H16O6/c1-16(21)6-10-8(5-12(16)18)15(20)13-9(14(10)19)3-7(22-2)4-11(13)17/h3-4,12,17-18,21H,5-6H2,1-2H3/t12-,16+/m1/s1
SMILES COc1cc(O)c2c(c1)C(=O)C1=C(C2=O)C[C@H]([C@@](C1)(C)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   304.09 Volume:   296.545
?
Van der Waals volume.
Dense:   1.025 LogP:   2.031
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.153
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.097
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   18.0
TPSA:   104.06
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   3.0 Rings:   3.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.714 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.758 Fsp3:   0.375
MCE-18:   70.636
?
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:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   1
Colloidal aggregators:   0.123 Fluc inhibitor:   0.273
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.681
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.248
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.191 Promiscuous compounds:   0.433

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.1 MDCK Permeability:   -4.729
Pgp-inhibitor:   0.01 Pgp-substrate:   0.005
PAMPA:   0.997
?
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):   0.073
20% Bioavailability (F20%):   0.004 30% Bioavailability (F30%):   0.009
50% Bioavailability (F50%):   0.252

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.757
Plasma Protein Binding (PPB):   88.955% Volume Distribution (VD):   0.453
Fu: 12.22%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.918
OATP1B3 inhibitor:   0.986 BCRP inhibitor:   0.008
BSEP inhibitor:   0.934

ADMET: Metabolism

CYP1A2-inhibitor:   0.858 CYP1A2-substrate:   0.086
CYP2C19-inhibitor:   0.053 CYP2C19-substrate:   0.003
CYP2C9-inhibitor:   0.093 CYP2C9-substrate:   0.543
CYP2D6-inhibitor:   0.002 CYP2D6-substrate:   0.157
CYP3A4-inhibitor:   0.001 CYP3A4-substrate:   0.008
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.486
HLM stability:   0.532
?
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):  5.182 Half-life (T1/2):  1.972

ADMET: Toxicity

hERG Blockers:  0.025 hERG Blockers (10um):  0.15
Human Hepatotoxicity (H-HT):  0.923 Drug-induced Liver Injury (DILI):  0.877
AMES Toxicity:  0.878 Rat Oral Acute Toxicity:  0.298
Maximum Recommended Daily Dose:  0.7 Skin Sensitization:  0.898
Carcinogencity:  0.94 Eye Corrosion:  0.0
Eye Irritation:  0.543 Respiratory Toxicity:  0.031
Drug-induced Neurotoxicity:  0.154 Ototoxicity:  0.816
Hematotoxicity:  0.905 Drug-induced Nephrotoxicity:  0.976
Genotoxicity:  0.981 RPMI-8226 Immunitoxicity:  0.365
A549 Cytotoxicity:  0.126 Hek293 Cytotoxicity:  0.558
BCF:   1.394
?
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:   3.711
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.014
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.263
?
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
NPO32908 Alternaria sp. Species Pleosporaceae Eukaryota n.a. n.a. n.a. PMID[18494522]
NPO32908 Alternaria sp. Species Pleosporaceae Eukaryota n.a. n.a. n.a. PMID[22276679]
NPO33215 Stemphylium sp. 33231 Species Pleosporaceae Eukaryota n.a. South China Sea n.a. PMID[25136754]
NPO32908 Alternaria sp. Species Pleosporaceae Eukaryota n.a. n.a. n.a. PMID[25265160]
NPO32908 Alternaria sp. Species Pleosporaceae Eukaryota n.a. n.a. n.a. PMID[26841051]
NPO32908 Alternaria sp. Species Pleosporaceae Eukaryota n.a. n.a. n.a. PMID[30794407]
NPO32908 Alternaria sp. Species Pleosporaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO33215 Stemphylium sp. 33231 Species Pleosporaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]

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
NPT393 Cell line HCT-116 Homo sapiens IC50 > 100000.0 nM PMID[24216090]
NPT306 Cell line PC-3 Homo sapiens IC50 > 100000.0 nM PMID[20643902]
NPT65 Cell line HepG2 Homo sapiens IC50 > 100000.0 nM PMID[21513292]
NPT81 Cell line A549 Homo sapiens IC50 > 10000.0 nM DrugMatrix in vitro pharmacology data
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 > 100000.0 nM PMID[22276679]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 > 10000.0 nM PMID[25136754]
NPT79 Organism Bacillus subtilis Bacillus subtilis MIC = 7800.0 nM DOI[10.6019/CHEMBL1201861]
NPT565 Organism Vibrio parahaemolyticus Vibrio parahaemolyticus MIC = 2.5 ug.mL-1 PMID[37011553]
NPT565 Organism Vibrio parahaemolyticus Vibrio parahaemolyticus MIC = 25000.0 nM PMID[37011553]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC = 12.5 ug.mL-1 DrugMatrix in vivo data: Hematology
NPT18 Organism Pseudomonas aeruginosa Pseudomonas aeruginosa MIC = 12.5 ug.mL-1 PMID[10924166]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC = 7800.0 nM PMID[22405285]
NPT19 Organism Escherichia coli Escherichia coli MIC = 7800.0 nM PMID[23691978]
NPT29524 Organism Vibrio anguillarum Vibrio anguillarum MIC = 5.0 ug.mL-1 PMID[37011553]
NPT2 Others Unspecified n.a. IC50 > 100000 nM PMID[22276679]
NPT3146 Organism Micrococcus Micrococcus MIC > 10000.0 nM PMID[12828457]
NPT1238 Organism Staphylococcus Staphylococcus MIC > 10000.0 nM PMID[11000021]
NPT314 Organism Bacillus cereus Bacillus cereus MIC > 10000.0 nM Open TG-GATES in vivo data: Hematology
NPT3147 Organism Kocuria rhizophila Kocuria rhizophila MIC = 7800.0 nM PMID[23916149]
NPT742 Organism Influenza A virus Influenza A virus IC50 = 7.82 ug.mL-1 PMID[34438338]

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 NPC132990 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
0.7308 Intermediate Similarity NPC603318
0.717 Intermediate Similarity NPC46882
0.717 Intermediate Similarity NPC601158
0.7115 Intermediate Similarity NPC605835
0.6557 Remote Similarity NPC472051
0.6491 Remote Similarity NPC600462
0.6379 Remote Similarity NPC472050
0.6038 Remote Similarity NPC480618
0.6029 Remote Similarity NPC472057
0.5714 Remote Similarity NPC155686
0.5714 Remote Similarity NPC602483
0.5614 Remote Similarity NPC610271
0.55 Remote Similarity NPC486423
0.55 Remote Similarity NPC486424
0.55 Remote Similarity NPC482541
0.5333 Remote Similarity NPC480607
0.5283 Remote Similarity NPC481949
0.5167 Remote Similarity NPC486471

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC132990 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