Natural Product: NPC471984

Natural Product IDNPC471984
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 XWLMKXLXTCJNHF-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL3314709
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0000123] Benzopyrans
        • [CHEMONTID:0003410] 1-benzopyrans
          • [CHEMONTID:0003543] Pyranochromenes

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 XWLMKXLXTCJNHF-UHFFFAOYSA-N
Standard InCHI InChI=1S/C20H16O6/c1-20(2)8-7-13-16(26-20)9-14(22)18-15(23)10-17(25-19(13)18)24-12-5-3-11(21)4-6-12/h3-10,21-22H,1-2H3
SMILES CC1(C=CC2=C(O1)C=C(C3=C2OC(=CC3=O)OC4=CC=C(C=C4)O)O)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   352.09 Volume:   349.264
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Van der Waals volume.
Dense:   1.008 LogP:   3.335
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.024
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.788
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The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   23.0
TPSA:   89.13
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Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   2.0 Rings:   4.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.719 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.012 Fsp3:   0.15
MCE-18:   50.087
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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:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.593 Fluc inhibitor:   0.268
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.929
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.802
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.386 Promiscuous compounds:   0.351

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.898 MDCK Permeability:   -4.736
Pgp-inhibitor:   0.139 Pgp-substrate:   0.022
PAMPA:   0.812
?
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%):   0.903 30% Bioavailability (F30%):   0.966
50% Bioavailability (F50%):   0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.071 MRP1:   0.965
Plasma Protein Binding (PPB):   98.02% Volume Distribution (VD):   0.027
Fu: 1.542%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   0.914 BCRP inhibitor:   0.137
BSEP inhibitor:   0.999

ADMET: Metabolism

CYP1A2-inhibitor:   0.029 CYP1A2-substrate:   0.931
CYP2C19-inhibitor:   0.005 CYP2C19-substrate:   0.007
CYP2C9-inhibitor:   0.448 CYP2C9-substrate:   0.009
CYP2D6-inhibitor:   0.496 CYP2D6-substrate:   0.564
CYP3A4-inhibitor:   0.008 CYP3A4-substrate:   0.924
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.669
?
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):  5.519 Half-life (T1/2):  0.898

ADMET: Toxicity

hERG Blockers:  0.195 hERG Blockers (10um):  0.652
Human Hepatotoxicity (H-HT):  0.589 Drug-induced Liver Injury (DILI):  0.941
AMES Toxicity:  0.747 Rat Oral Acute Toxicity:  0.515
Maximum Recommended Daily Dose:  0.862 Skin Sensitization:  0.708
Carcinogencity:  0.813 Eye Corrosion:  0.012
Eye Irritation:  0.968 Respiratory Toxicity:  0.862
Drug-induced Neurotoxicity:  0.123 Ototoxicity:  0.183
Hematotoxicity:  0.095 Drug-induced Nephrotoxicity:  0.08
Genotoxicity:  0.838 RPMI-8226 Immunitoxicity:  0.054
A549 Cytotoxicity:  0.339 Hek293 Cytotoxicity:  0.824
BCF:   1.575
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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:   4.303
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.575
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.998
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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
NPO23024 Epimedium koreanum Species Berberidaceae Eukaryota n.a. n.a. n.a. PMID[12081149]
NPO23024 Epimedium koreanum Species Berberidaceae Eukaryota n.a. root n.a. PMID[22051934]
NPO23024 Epimedium koreanum Species Berberidaceae Eukaryota aerial parts herbal garden of Chungbuk National University, Cheongju, Korea 2012-Oct PMID[24963714]
NPO23024 Epimedium koreanum Species Berberidaceae Eukaryota n.a. aerial part n.a. Database[Article]
NPO23024 Epimedium koreanum Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23024 Epimedium koreanum Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO23024 Epimedium koreanum Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO23024 Epimedium koreanum Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO23024 Epimedium koreanum Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO23024 Epimedium koreanum Species Berberidaceae 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
NPT113 Cell line RAW264.7 Mus musculus IC50 > 50000.0 nM PMID[23327668]

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 NPC471984 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
0.6957 Remote Similarity NPC482020
0.6164 Remote Similarity NPC482022
0.5972 Remote Similarity NPC293852
0.5833 Remote Similarity NPC24673
0.5634 Remote Similarity NPC242100
0.5616 Remote Similarity NPC211811
0.5541 Remote Similarity NPC482019
0.5467 Remote Similarity NPC166757
0.5467 Remote Similarity NPC170492
0.5333 Remote Similarity NPC120105
0.5195 Remote Similarity NPC57393
0.5195 Remote Similarity NPC482021
0.5132 Remote Similarity NPC275122
0.5132 Remote Similarity NPC55662
0.5132 Remote Similarity NPC5322
0.5067 Remote Similarity NPC600644
0.5063 Remote Similarity NPC15435

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC471984 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