Natural Product: NPC232164

Natural Product IDNPC232164
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 4-Hydroxymedicarpin
IUPAC Name (6aR,11aR)-9-methoxy-6a,11a-dihydro-6H-[1]benzofuro[3,2-c]chromene-3,4-diol
Synonyms 4-Hydroxymedicarpin
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL253466
PubChem CID 13940834
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0002506] Isoflavonoids
        • [CHEMONTID:0002617] Furanoisoflavonoids
          • [CHEMONTID:0001608] Pterocarpans

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 YRFDJOAWSXSLMG-NHYWBVRUSA-N
Standard InCHI InChI=1S/C16H14O5/c1-19-8-2-3-9-11-7-20-16-10(4-5-12(17)14(16)18)15(11)21-13(9)6-8/h2-6,11,15,17-18H,7H2,1H3/t11-,15-/m0/s1
SMILES COc1ccc2c(c1)O[C@@H]1[C@H]2COc2c1ccc(c2O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   286.08 Volume:   279.199
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Van der Waals volume.
Dense:   1.025 LogP:   2.84
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.912
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.366
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The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   20.0
TPSA:   68.15
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Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   2.0 Rings:   4.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.789 GASA:   1.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.355 Fsp3:   0.25
MCE-18:   69.3
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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:   1 PAINS Alert:   1
Colloidal aggregators:   0.718 Fluc inhibitor:   0.972
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.152
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.299
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.435 Promiscuous compounds:   0.608

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.961 MDCK Permeability:   -4.759
Pgp-inhibitor:   0.01 Pgp-substrate:   0.112
PAMPA:   0.031
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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):   0.022
20% Bioavailability (F20%):   0.833 30% Bioavailability (F30%):   0.848
50% Bioavailability (F50%):   0.968

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.438 MRP1:   0.8
Plasma Protein Binding (PPB):   83.328% Volume Distribution (VD):   -0.321
Fu: 16.432%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.987
OATP1B3 inhibitor:   0.989 BCRP inhibitor:   0.721
BSEP inhibitor:   0.419

ADMET: Metabolism

CYP1A2-inhibitor:   0.899 CYP1A2-substrate:   0.104
CYP2C19-inhibitor:   0.182 CYP2C19-substrate:   0.154
CYP2C9-inhibitor:   0.993 CYP2C9-substrate:   0.026
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.911
CYP3A4-inhibitor:   0.006 CYP3A4-substrate:   0.977
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.036
HLM stability:   0.827
?
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):  11.74 Half-life (T1/2):  2.379

ADMET: Toxicity

hERG Blockers:  0.158 hERG Blockers (10um):  0.622
Human Hepatotoxicity (H-HT):  0.533 Drug-induced Liver Injury (DILI):  0.745
AMES Toxicity:  0.677 Rat Oral Acute Toxicity:  0.279
Maximum Recommended Daily Dose:  0.351 Skin Sensitization:  0.84
Carcinogencity:  0.53 Eye Corrosion:  0.06
Eye Irritation:  0.978 Respiratory Toxicity:  0.569
Drug-induced Neurotoxicity:  0.189 Ototoxicity:  0.58
Hematotoxicity:  0.223 Drug-induced Nephrotoxicity:  0.326
Genotoxicity:  0.208 RPMI-8226 Immunitoxicity:  0.049
A549 Cytotoxicity:  0.486 Hek293 Cytotoxicity:  0.343
BCF:   1.252
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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:   3.745
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.427
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.636
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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
NPO29804 Nepalese propolis n.a. n.a. n.a. n.a. n.a. n.a. PMID[15974608]
NPO33288 Brazilian Red Propolis Strain n.a. n.a. n.a. Brazilian n.a. PMID[17950610]
NPO33288 Brazilian Red Propolis Strain n.a. n.a. n.a. Brazilian n.a. PMID[18440233]
NPO33288 Brazilian Red Propolis Strain n.a. n.a. n.a. n.a. n.a. PMID[26938776]
NPO33288 Brazilian Red Propolis Strain n.a. n.a. n.a. n.a. n.a. PMID[32525315]
NPO33288 Brazilian Red Propolis Strain n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO29804 Nepalese propolis n.a. n.a. n.a. 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
NPT461 Cell line PANC-1 Homo sapiens CD100 = 25.0 uM PMID[25333996]
NPT81 Cell line A549 Homo sapiens IC50 > 100000.0 nM PubChem BioAssay data set
NPT165 Cell line HeLa Homo sapiens IC50 > 100000.0 nM PMID[24370114]
NPT453 Cell line HT-1080 Homo sapiens IC50 > 100000.0 nM PubChem BioAssay data set
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 > 100000.0 nM PMID[18440233]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 54100.0 nM PMID[18440233]
NPT20763 Cell line J774.1 Mus musculus IC50 = 5400.0 nM PMID[15974608]

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 NPC232164 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
1.0 High Similarity NPC473739
0.7736 Intermediate Similarity NPC309124
0.7091 Intermediate Similarity NPC184797
0.7091 Intermediate Similarity NPC39064
0.7091 Intermediate Similarity NPC47283
0.6667 Remote Similarity NPC294156
0.6667 Remote Similarity NPC256015
0.6441 Remote Similarity NPC605383
0.6207 Remote Similarity NPC32633
0.6182 Remote Similarity NPC474478
0.6182 Remote Similarity NPC606219
0.6 Remote Similarity NPC17343
0.5385 Remote Similarity NPC71288
0.5385 Remote Similarity NPC301961
0.5323 Remote Similarity NPC236306
0.5246 Remote Similarity NPC27495
0.5143 Remote Similarity NPC108674
0.5088 Remote Similarity NPC471215
0.5088 Remote Similarity NPC262573
0.5079 Remote Similarity NPC300798
0.5079 Remote Similarity NPC58137

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC232164 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