Natural Product: NPC57315

Natural Product IDNPC57315
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 TYAYDVXOPBERFS-RTWAWAEBSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 636845
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0003405] 2-arylbenzofuran flavonoids

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 TYAYDVXOPBERFS-RTWAWAEBSA-N
Standard InCHI InChI=1S/C21H16O5/c22-11-12-1-6-19-18(7-12)20(14-8-16(24)10-17(25)9-14)21(26-19)13-2-4-15(23)5-3-13/h1-11,20-21,23-25H/t20-,21+/m1/s1
SMILES c1cc2c(cc1C=O)[C@@H](c1cc(cc(c1)O)O)[C@H](c1ccc(cc1)O)O2

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   348.1 Volume:   355.133
?
Van der Waals volume.
Dense:   0.98 LogP:   3.117
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.897
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.822
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   23.0
TPSA:   86.99
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   3.0 Rings:   4.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.625 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.292 Fsp3:   0.095
MCE-18:   69.826
?
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:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.998 Fluc inhibitor:   0.795
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.101
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.381
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.664 Promiscuous compounds:   0.17

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.972 MDCK Permeability:   -4.758
Pgp-inhibitor:   0.028 Pgp-substrate:   0.057
PAMPA:   0.029
?
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):   0.0
20% Bioavailability (F20%):   0.893 30% Bioavailability (F30%):   0.975
50% Bioavailability (F50%):   0.998

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.008 MRP1:   0.012
Plasma Protein Binding (PPB):   88.658% Volume Distribution (VD):   0.195
Fu: 13.305%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.996
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.089
BSEP inhibitor:   0.845

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.018
CYP2C19-inhibitor:   0.04 CYP2C19-substrate:   1.0
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.998
CYP3A4-inhibitor:   0.345 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.037
?
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):  11.02 Half-life (T1/2):  1.424

ADMET: Toxicity

hERG Blockers:  0.386 hERG Blockers (10um):  0.713
Human Hepatotoxicity (H-HT):  0.924 Drug-induced Liver Injury (DILI):  0.078
AMES Toxicity:  0.479 Rat Oral Acute Toxicity:  0.411
Maximum Recommended Daily Dose:  0.897 Skin Sensitization:  0.85
Carcinogencity:  0.233 Eye Corrosion:  0.026
Eye Irritation:  0.992 Respiratory Toxicity:  0.639
Drug-induced Neurotoxicity:  0.748 Ototoxicity:  0.484
Hematotoxicity:  0.042 Drug-induced Nephrotoxicity:  0.28
Genotoxicity:  0.99 RPMI-8226 Immunitoxicity:  0.038
A549 Cytotoxicity:  0.469 Hek293 Cytotoxicity:  0.953
BCF:   1.106
?
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:   4.075
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.019
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.754
?
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
NPO29141 Panax ginseng Species Araliaceae Eukaryota n.a. n.a. n.a. DOI[10.1016/j.jarmap.2018.11.004]
NPO5577 Methylobacterium rhodinum Species Methylobacteriaceae Bacteria n.a. n.a. n.a. PMID[15933032]
NPO29141 Panax ginseng Species Araliaceae Eukaryota n.a. leaf n.a. PMID[18409045]
NPO11769 Eupatorium adenophorum Species Asteraceae Eukaryota Leaves n.a. n.a. PMID[18620454]
NPO29034 Suberea mollis Species Aplysinellidae Eukaryota n.a. red sea n.a. PMID[18656986]
NPO25024 Lycoris traubii Species Amaryllidaceae Eukaryota n.a. n.a. n.a. PMID[19013823]
NPO29141 Panax ginseng Species Araliaceae Eukaryota flower buds n.a. n.a. PMID[19926279]
NPO29141 Panax ginseng Species Araliaceae Eukaryota n.a. root n.a. PMID[2092947]
NPO29141 Panax ginseng Species Araliaceae Eukaryota berry n.a. n.a. PMID[21216145]
NPO29034 Suberea mollis Species Aplysinellidae Eukaryota n.a. Red Sea n.a. PMID[21542602]
NPO29034 Suberea mollis Species Aplysinellidae Eukaryota n.a. n.a. n.a. PMID[21542602]
NPO29141 Panax ginseng Species Araliaceae Eukaryota leaves n.a. n.a. PMID[24290061]
NPO29141 Panax ginseng Species Araliaceae Eukaryota n.a. n.a. n.a. PMID[24968750]
NPO29141 Panax ginseng Species Araliaceae Eukaryota n.a. n.a. n.a. PMID[25152999]
NPO29141 Panax ginseng Species Araliaceae Eukaryota stems-leaves n.a. n.a. PMID[26420067]
NPO29141 Panax ginseng Species Araliaceae Eukaryota n.a. stem n.a. PMID[27914541]
NPO29141 Panax ginseng Species Araliaceae Eukaryota Flower Buds n.a. n.a. PMID[28345906]
NPO29141 Panax ginseng Species Araliaceae Eukaryota n.a. n.a. n.a. PMID[32129622]
NPO5577 Methylobacterium rhodinum Species Methylobacteriaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO29141 Panax ginseng Species Araliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28862 Crotalaria anagyroides Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29311 Securinega melanthesoides Species Phyllanthaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11769 Eupatorium adenophorum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26970 Lygodium flexuosum Species Lygodiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29034 Suberea mollis Species Aplysinellidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29003 Croton poilanei Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29362 Euonymus sachalinensis Species Celastraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28984 Dasymaschalon sootepense Species Annonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14557 Dictyopteris undulata Species Dictyotaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26970 Lygodium flexuosum Species Lygodiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO29141 Panax ginseng Species Araliaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO28862 Crotalaria anagyroides Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO29141 Panax ginseng Species Araliaceae Eukaryota n.a. n.a. n.a. Database[MetaboLights]
NPO26970 Lygodium flexuosum Species Lygodiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO29141 Panax ginseng Species Araliaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO11769 Eupatorium adenophorum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO28862 Crotalaria anagyroides Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO29449 Boehmeria nivea Species Urticaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO29141 Panax ginseng Species Araliaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO29449 Boehmeria nivea Species Urticaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO29141 Panax ginseng Species Araliaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO26970 Lygodium flexuosum Species Lygodiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21700 Capsicum tetragonum Species Solanaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14557 Dictyopteris undulata Species Dictyotaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28820 Saccharum spontaneum Species Poaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25024 Lycoris traubii Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28984 Dasymaschalon sootepense Species Annonaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11769 Eupatorium adenophorum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29199 Lobophytum chevalieri Species Alcyoniidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28862 Crotalaria anagyroides Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29379 Felicia erigeroides Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29188 Guatteria melosma Species Annonaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29046 Tsuga mertensiana Species Pinaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29362 Euonymus sachalinensis Species Celastraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29413 Lupinus paniculatus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29311 Securinega melanthesoides Species Phyllanthaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28754 Thelephora palmata Species Thelephoraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28666 Strychnos staudtii Species Loganiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29449 Boehmeria nivea Species Urticaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29003 Croton poilanei Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5577 Methylobacterium rhodinum Species Methylobacteriaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO28783 Dictyoloma incanescens Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29034 Suberea mollis Species Aplysinellidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29141 Panax ginseng Species Araliaceae 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

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 NPC57315 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
0.8148 Intermediate Similarity NPC478982
0.7407 Intermediate Similarity NPC125579
0.6557 Remote Similarity NPC480680
0.6032 Remote Similarity NPC480677
0.5909 Remote Similarity NPC112819
0.5909 Remote Similarity NPC133209
0.5909 Remote Similarity NPC6702
0.5862 Remote Similarity NPC175765
0.5667 Remote Similarity NPC141717
0.5397 Remote Similarity NPC480681
0.5385 Remote Similarity NPC478879
0.5385 Remote Similarity NPC478881
0.5323 Remote Similarity NPC76424
0.5323 Remote Similarity NPC15109
0.5323 Remote Similarity NPC291103
0.5323 Remote Similarity NPC11727
0.5286 Remote Similarity NPC261896
0.5156 Remote Similarity NPC157081
0.5075 Remote Similarity NPC610035

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC57315 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