Natural Product: NPC181049

Natural Product IDNPC181049
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 8-Hydroxypinoresinol
IUPAC Name (3R,3aS,6S,6aR)-3,6-bis(4-hydroxy-3-methoxyphenyl)-3,4,6,6a-tetrahydro-1H-furo[3,4-c]furan-3a-ol
Synonyms 8-Hydroxypinoresinol
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL471274
PubChem CID 3010930
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0001392] Lignans, neolignans and related compounds
      • [CHEMONTID:0003686] Furanoid lignans

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 CICMVLOHBZPXIT-WNISUXOKSA-N
Standard InCHI InChI=1S/C20H22O7/c1-24-16-7-11(3-5-14(16)21)18-13-9-26-19(20(13,23)10-27-18)12-4-6-15(22)17(8-12)25-2/h3-8,13,18-19,21-23H,9-10H2,1-2H3/t13-,18-,19-,20-/m1/s1
SMILES COc1cc(ccc1O)[C@H]1OC[C@]2([C@@H]1CO[C@@H]2c1ccc(c(c1)OC)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   374.14 Volume:   365.963
?
Van der Waals volume.
Dense:   1.022 LogP:   0.931
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.237
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.104
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   21.0
TPSA:   97.61
?
Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   3.0 Rings:   4.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.755 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.882 Fsp3:   0.4
MCE-18:   82.286
?
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:   0
Colloidal aggregators:   0.135 Fluc inhibitor:   0.34
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.028
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.102
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.221 Promiscuous compounds:   0.187

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.264 MDCK Permeability:   -4.791
Pgp-inhibitor:   0.003 Pgp-substrate:   0.117
PAMPA:   0.139
?
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):   0.003
20% Bioavailability (F20%):   0.684 30% Bioavailability (F30%):   0.684
50% Bioavailability (F50%):   0.997

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.008 MRP1:   0.876
Plasma Protein Binding (PPB):   73.913% Volume Distribution (VD):   -0.163
Fu: 27.568%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.997
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   0.374
BSEP inhibitor:   0.123

ADMET: Metabolism

CYP1A2-inhibitor:   0.999 CYP1A2-substrate:   0.003
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.001
CYP2C9-inhibitor:   0.036 CYP2C9-substrate:   0.058
CYP2D6-inhibitor:   0.365 CYP2D6-substrate:   0.587
CYP3A4-inhibitor:   0.935 CYP3A4-substrate:   0.293
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.427
HLM stability:   0.002
?
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):  6.147 Half-life (T1/2):  2.791

ADMET: Toxicity

hERG Blockers:  0.043 hERG Blockers (10um):  0.406
Human Hepatotoxicity (H-HT):  0.639 Drug-induced Liver Injury (DILI):  0.689
AMES Toxicity:  0.92 Rat Oral Acute Toxicity:  0.404
Maximum Recommended Daily Dose:  0.512 Skin Sensitization:  0.981
Carcinogencity:  0.555 Eye Corrosion:  0.099
Eye Irritation:  0.994 Respiratory Toxicity:  0.51
Drug-induced Neurotoxicity:  0.484 Ototoxicity:  0.23
Hematotoxicity:  0.22 Drug-induced Nephrotoxicity:  0.392
Genotoxicity:  0.79 RPMI-8226 Immunitoxicity:  0.184
A549 Cytotoxicity:  0.646 Hek293 Cytotoxicity:  0.61
BCF:   1.081
?
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:   3.41
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.501
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.897
?
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
NPO8258 Camellia sinensis Species Theaceae Eukaryota n.a. n.a. n.a. PMID[ 16712885]
NPO8258 Camellia sinensis Species Theaceae Eukaryota n.a. n.a. n.a. DOI[10.1016/j.foodchem.2013.08.121]
NPO14102 Kadsura interior Species Schisandraceae Eukaryota n.a. n.a. n.a. PMID[12350139]
NPO15563 Valeriana prionophylla Species Caprifoliaceae Eukaryota n.a. n.a. n.a. PMID[15270567]
NPO8258 Camellia sinensis Species Theaceae Eukaryota Flowers n.a. n.a. PMID[16180814]
NPO8258 Camellia sinensis Species Theaceae Eukaryota seeds Shizuoka prefecture, Japan n.a. PMID[16499314]
NPO8258 Camellia sinensis Species Theaceae Eukaryota n.a. n.a. n.a. PMID[18068204]
NPO1743 Neurospora terricola Species Sordariaceae Eukaryota n.a. n.a. n.a. PMID[19795843]
NPO8258 Camellia sinensis Species Theaceae Eukaryota n.a. n.a. n.a. PMID[21434603]
NPO8258 Camellia sinensis Species Theaceae Eukaryota n.a. flower n.a. PMID[21922925]
NPO8258 Camellia sinensis Species Theaceae Eukaryota flower buds n.a. n.a. PMID[21925888]
NPO8258 Camellia sinensis Species Theaceae Eukaryota leaves n.a. n.a. PMID[22377672]
NPO33401 schisandra sphenathera Species Schisandraceae Eukaryota stems n.a. n.a. PMID[23237974]
NPO8258 Camellia sinensis Species Theaceae Eukaryota n.a. leaf n.a. PMID[23265489]
NPO8258 Camellia sinensis Species Theaceae Eukaryota Leaves Bandung, West Java, Indonesia PMID[23621359]
NPO12498 Carpesium cernuum Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[27668963]
NPO12498 Carpesium cernuum Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[33810440]
NPO8258 Camellia sinensis Species Theaceae Eukaryota n.a. n.a. n.a. PMID[37255739]
NPO14102 Kadsura interior Species Schisandraceae Eukaryota n.a. stem n.a. PMID[8946749]
NPO15006 Asparagus africanus Species Asparagaceae Eukaryota n.a. n.a. n.a. PMID[9358645]
NPO11868 Malassezia furfur Species Malasseziaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8258 Camellia sinensis Species Theaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12736 Galleria mellonella Species Pyralidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14102 Kadsura interior Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15563 Valeriana prionophylla Species Caprifoliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29013 Annulohypoxylon cohaerens Species Xylariaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15006 Asparagus africanus Species Asparagaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13530 Thorectandra excavatus Species Thorectidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1743 Neurospora terricola Species Sordariaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12498 Carpesium cernuum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14870 Cytisus austriacus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8258 Camellia sinensis Species Theaceae Eukaryota Shoot n.a. n.a. Database[FooDB]
NPO8258 Camellia sinensis Species Theaceae Eukaryota Cotyledon n.a. n.a. Database[FooDB]
NPO8258 Camellia sinensis Species Theaceae Eukaryota Leaf n.a. n.a. Database[FooDB]
NPO8258 Camellia sinensis Species Theaceae Eukaryota Leaf Essent. Oil n.a. n.a. Database[FooDB]
NPO8258 Camellia sinensis Species Theaceae Eukaryota Plant n.a. n.a. Database[FooDB]
NPO8258 Camellia sinensis Species Theaceae Eukaryota Seed n.a. n.a. Database[FooDB]
NPO8258 Camellia sinensis Species Theaceae Eukaryota Seed Oil n.a. n.a. Database[FooDB]
NPO8258 Camellia sinensis Species Theaceae Eukaryota Stem n.a. n.a. Database[FooDB]
NPO8258 Camellia sinensis Species Theaceae Eukaryota n.a. n.a. Database[FooDB]
NPO8258 Camellia sinensis Species Theaceae Eukaryota n.a. n.a. Database[FooDB]
NPO8258 Camellia sinensis Species Theaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO6080 Ericerus pela Species Coccidae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO11886 Hemerocallis citrina Species Asphodelaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO14102 Kadsura interior Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO11886 Hemerocallis citrina Species Asphodelaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO8258 Camellia sinensis Species Theaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO14102 Kadsura interior Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO6080 Ericerus pela Species Coccidae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO8258 Camellia sinensis Species Theaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO16314.1 Clematis terniflora var. mandshurica Varieties Ranunculaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO11868 Malassezia furfur Species Malasseziaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14901 Neocosmospora tenuicristata Species Nectriaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6514 Desmotrichum fimbriatum n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO1302 Orobanche speciosa Species Orobanchaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14870 Cytisus austriacus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12736 Galleria mellonella Species Pyralidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10825 Nerine sarniensis Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9577 Triclisia dictyophylla Species Menispermaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11886 Hemerocallis citrina Species Asphodelaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6012 Dumoria heckelii n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO16314.1 Clematis terniflora var. mandshurica Varieties Ranunculaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO35 Zanthoxylum dinklagei Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29013 Annulohypoxylon cohaerens Species Xylariaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14102 Kadsura interior Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15563 Valeriana prionophylla Species Caprifoliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6080 Ericerus pela Species Coccidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15006 Asparagus africanus Species Asparagaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10298 Symbiodinium microadriaticum Species Symbiodiniaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1743 Neurospora terricola Species Sordariaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1967 Solanum chilense Species Solanaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11775 Ophelia neglecta Species Opheliidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8258 Camellia sinensis Species Theaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25336 Halichondria melanadocia Species Halichondriidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16099 Penstemon newberryi Species Plantaginaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12498 Carpesium cernuum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9871.1 Ficus benghalensis var. krishnae Varieties Moraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13530 Thorectandra excavatus Species Thorectidae 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
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Activity = 5.1 mM PMID[15270567]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Activity = 6.31 mM PMID[15270567]
NPT177 Tissue Aorta Rattus norvegicus Activity = 24.4 % PMID[15270567]
NPT177 Tissue Aorta Rattus norvegicus Activity = 29.0 % PMID[15270567]

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 NPC181049 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
0.6852 Remote Similarity NPC207400
0.6479 Remote Similarity NPC112861
0.6275 Remote Similarity NPC4940
0.6078 Remote Similarity NPC115207
0.6078 Remote Similarity NPC158079
0.6078 Remote Similarity NPC228346
0.6078 Remote Similarity NPC40432
0.6078 Remote Similarity NPC161557
0.6038 Remote Similarity NPC147379
0.5893 Remote Similarity NPC478955
0.5893 Remote Similarity NPC478700
0.5873 Remote Similarity NPC471988
0.5862 Remote Similarity NPC101807
0.5636 Remote Similarity NPC126409
0.5636 Remote Similarity NPC99572
0.5574 Remote Similarity NPC277804
0.5574 Remote Similarity NPC23646
0.5574 Remote Similarity NPC485397
0.5472 Remote Similarity NPC242807
0.5472 Remote Similarity NPC153739
0.5455 Remote Similarity NPC469480
0.5385 Remote Similarity NPC282703
0.5385 Remote Similarity NPC184733
0.5385 Remote Similarity NPC128208
0.5385 Remote Similarity NPC129570
0.5385 Remote Similarity NPC63238
0.5385 Remote Similarity NPC602603
0.5345 Remote Similarity NPC27843
0.5345 Remote Similarity NPC7171
0.5185 Remote Similarity NPC142985
0.5167 Remote Similarity NPC223185
0.5167 Remote Similarity NPC610778
0.5161 Remote Similarity NPC272
0.5161 Remote Similarity NPC187998
0.5161 Remote Similarity NPC77040
0.5161 Remote Similarity NPC257582
0.5161 Remote Similarity NPC241522
0.5161 Remote Similarity NPC485398

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC181049 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