Natural Product: NPC285623

Natural Product IDNPC285623
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Corylifol E
IUPAC Name 7-hydroxy-3-[(2R,3R)-3-hydroxy-2-(2-hydroxypropan-2-yl)-2,3-dihydro-1-benzofuran-5-yl]chromen-4-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL3577252
PubChem CID 71769735
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0002506] Isoflavonoids
        • [CHEMONTID:0002901] Isoflav-2-enes
          • [CHEMONTID:0000494] Isoflavones

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 BEELJZPOZYDTHN-RTBURBONSA-N
Standard InCHI InChI=1S/C20H18O6/c1-20(2,24)19-18(23)13-7-10(3-6-15(13)26-19)14-9-25-16-8-11(21)4-5-12(16)17(14)22/h3-9,18-19,21,23-24H,1-2H3/t18-,19-/m1/s1
SMILES CC(C)([C@H]1[C@@H](c2cc(ccc2O1)c1coc2cc(ccc2c1=O)O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   354.11 Volume:   351.9
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Van der Waals volume.
Dense:   1.006 LogP:   1.746
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.963
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.772
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The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   22.0
TPSA:   100.13
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Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   3.0 Rings:   4.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.654 GASA:   1.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.496 Fsp3:   0.25
MCE-18:   79.0
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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:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.627 Fluc inhibitor:   0.969
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.961
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.221
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.255 Promiscuous compounds:   0.316

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.022 MDCK Permeability:   -4.753
Pgp-inhibitor:   0.709 Pgp-substrate:   0.262
PAMPA:   0.195
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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):   0.007
20% Bioavailability (F20%):   0.147 30% Bioavailability (F30%):   0.746
50% Bioavailability (F50%):   0.925

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.001 MRP1:   0.48
Plasma Protein Binding (PPB):   85.287% Volume Distribution (VD):   -0.303
Fu: 11.731%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.992
OATP1B3 inhibitor:   0.989 BCRP inhibitor:   0.57
BSEP inhibitor:   0.984

ADMET: Metabolism

CYP1A2-inhibitor:   0.005 CYP1A2-substrate:   0.654
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.084
CYP2C9-inhibitor:   0.05 CYP2C9-substrate:   0.609
CYP2D6-inhibitor:   0.729 CYP2D6-substrate:   0.002
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.001
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.999
HLM stability:   0.027
?
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):  6.888 Half-life (T1/2):  1.556

ADMET: Toxicity

hERG Blockers:  0.19 hERG Blockers (10um):  0.311
Human Hepatotoxicity (H-HT):  0.681 Drug-induced Liver Injury (DILI):  0.621
AMES Toxicity:  0.704 Rat Oral Acute Toxicity:  0.473
Maximum Recommended Daily Dose:  0.799 Skin Sensitization:  0.35
Carcinogencity:  0.829 Eye Corrosion:  0.001
Eye Irritation:  0.846 Respiratory Toxicity:  0.702
Drug-induced Neurotoxicity:  0.15 Ototoxicity:  0.69
Hematotoxicity:  0.254 Drug-induced Nephrotoxicity:  0.475
Genotoxicity:  0.973 RPMI-8226 Immunitoxicity:  0.065
A549 Cytotoxicity:  0.088 Hek293 Cytotoxicity:  0.64
BCF:   0.902
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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:   3.668
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.806
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.325
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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
NPO30150 Psoralea corylifolia Species Fabaceae Eukaryota seeds n.a. n.a. PMID[18359631]
NPO30150 Psoralea corylifolia Species Fabaceae Eukaryota Fruits n.a. n.a. PMID[25710081]
NPO30150 Psoralea corylifolia Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[3069958]
NPO30150 Psoralea corylifolia Species Fabaceae Eukaryota n.a. seed n.a. PMID[8759164]
NPO30150 Psoralea corylifolia Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO30150 Psoralea corylifolia Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO30150 Psoralea corylifolia Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]

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
NPT81 Cell line A549 Homo sapiens IC50 > 10000.0 nM PMID[16890435]
NPT111 Cell line K562 Homo sapiens IC50 > 10000.0 nM PMID[16890435]

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 NPC285623 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
0.7083 Intermediate Similarity NPC223701
0.7083 Intermediate Similarity NPC472583
0.6486 Remote Similarity NPC104406
0.6438 Remote Similarity NPC149875
0.64 Remote Similarity NPC7989
0.6119 Remote Similarity NPC209560
0.6119 Remote Similarity NPC490700
0.5942 Remote Similarity NPC12377
0.5857 Remote Similarity NPC80710
0.5694 Remote Similarity NPC35544
0.5606 Remote Similarity NPC242893
0.5584 Remote Similarity NPC266572
0.5538 Remote Similarity NPC234560
0.5467 Remote Similarity NPC215311
0.5429 Remote Similarity NPC203747
0.5429 Remote Similarity NPC609386
0.5417 Remote Similarity NPC139364
0.525 Remote Similarity NPC108859
0.5224 Remote Similarity NPC212767
0.5205 Remote Similarity NPC12175
0.5205 Remote Similarity NPC195763
0.5205 Remote Similarity NPC191741
0.5181 Remote Similarity NPC258035
0.5135 Remote Similarity NPC200060
0.5135 Remote Similarity NPC55162
0.5068 Remote Similarity NPC262623
0.5062 Remote Similarity NPC609101

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC285623 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