Natural Product: NPC223185

Natural Product IDNPC223185
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 4-Ketopinoresinol
IUPAC Name (3S,3aS,6S,6aR)-3,6-bis(4-hydroxy-3-methoxyphenyl)-3,3a,6,6a-tetrahydro-1H-furo[3,4-c]furan-4-one
Synonyms 4-Ketopinoresinol
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL479035
PubChem CID 44578390
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0001392] Lignans, neolignans and related compounds
      • [CHEMONTID:0001510] Lignan lactones

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 JOVBAVJQHJYOID-MDVLYUJXSA-N
Standard InCHI InChI=1S/C20H20O7/c1-24-15-7-10(3-5-13(15)21)18-12-9-26-19(17(12)20(23)27-18)11-4-6-14(22)16(8-11)25-2/h3-8,12,17-19,21-22H,9H2,1-2H3/t12-,17-,18+,19+/m0/s1
SMILES COc1cc(ccc1O)[C@@H]1[C@H]2CO[C@H](c3ccc(c(c3)OC)O)[C@H]2C(=O)O1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   372.12 Volume:   363.327
?
Van der Waals volume.
Dense:   1.024 LogP:   1.246
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.627
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.099
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   22.0
TPSA:   94.45
?
Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   2.0 Rings:   4.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.797 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.712 Fsp3:   0.35
MCE-18:   77.519
?
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:   0.387 Fluc inhibitor:   0.351
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.025
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.151
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.223 Promiscuous compounds:   0.272

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.717 MDCK Permeability:   -5.014
Pgp-inhibitor:   0.006 Pgp-substrate:   0.014
PAMPA:   0.017
?
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%):   0.06 30% Bioavailability (F30%):   0.069
50% Bioavailability (F50%):   0.695

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.025 MRP1:   0.924
Plasma Protein Binding (PPB):   89.979% Volume Distribution (VD):   -0.287
Fu: 12.249%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.972
OATP1B3 inhibitor:   0.987 BCRP inhibitor:   0.004
BSEP inhibitor:   0.12

ADMET: Metabolism

CYP1A2-inhibitor:   0.237 CYP1A2-substrate:   0.846
CYP2C19-inhibitor:   0.99 CYP2C19-substrate:   0.154
CYP2C9-inhibitor:   0.041 CYP2C9-substrate:   0.025
CYP2D6-inhibitor:   0.095 CYP2D6-substrate:   0.806
CYP3A4-inhibitor:   0.996 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.944
HLM stability:   0.45
?
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):  7.237 Half-life (T1/2):  2.555

ADMET: Toxicity

hERG Blockers:  0.053 hERG Blockers (10um):  0.37
Human Hepatotoxicity (H-HT):  0.475 Drug-induced Liver Injury (DILI):  0.821
AMES Toxicity:  0.585 Rat Oral Acute Toxicity:  0.121
Maximum Recommended Daily Dose:  0.15 Skin Sensitization:  0.973
Carcinogencity:  0.362 Eye Corrosion:  0.16
Eye Irritation:  0.986 Respiratory Toxicity:  0.23
Drug-induced Neurotoxicity:  0.142 Ototoxicity:  0.255
Hematotoxicity:  0.165 Drug-induced Nephrotoxicity:  0.53
Genotoxicity:  0.758 RPMI-8226 Immunitoxicity:  0.113
A549 Cytotoxicity:  0.23 Hek293 Cytotoxicity:  0.26
BCF:   0.982
?
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:   3.492
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.591
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.993
?
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
NPO21707 Trichosanthes kirilowii Species Cucurbitaceae Eukaryota n.a. seed n.a. DOI[10.1016/S0031-9422(00)97029-8]
NPO21707 Trichosanthes kirilowii Species Cucurbitaceae Eukaryota seeds n.a. n.a. PMID[18603435]
NPO21707 Trichosanthes kirilowii Species Cucurbitaceae Eukaryota Seeds n.a. n.a. PMID[20469887]
NPO20500 Hypericum elodeoides Species Hypericaceae Eukaryota n.a. n.a. n.a. PMID[31038949]
NPO20500 Hypericum elodeoides Species Hypericaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12126 Coix lacryma-jobi Species Poaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21707 Trichosanthes kirilowii Species Cucurbitaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21707 Trichosanthes kirilowii Species Cucurbitaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO12126 Coix lacryma-jobi Species Poaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO20500 Hypericum elodeoides Species Hypericaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO20500 Hypericum elodeoides Species Hypericaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO12126 Coix lacryma-jobi Species Poaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO21707 Trichosanthes kirilowii Species Cucurbitaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO12126 Coix lacryma-jobi Species Poaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO21707 Trichosanthes kirilowii Species Cucurbitaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO21707 Trichosanthes kirilowii Species Cucurbitaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO12126 Coix lacryma-jobi Species Poaceae 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
NPT81 Cell line A549 Homo sapiens IC50 > 40.0 ug.mL-1 PMID[18603435]
NPT147 Cell line SK-MEL-2 Homo sapiens IC50 = 20.0 ug.mL-1 PMID[18603435]
NPT659 Cell line SMMC-7721 Homo sapiens Activity < 50.0 % PMID[31038949]
NPT83 Cell line MCF7 Homo sapiens Activity < 50.0 % PMID[31038949]
NPT65 Cell line HepG2 Homo sapiens Activity < 50.0 % PMID[31038949]
NPT165 Cell line HeLa Homo sapiens Activity < 50.0 % PMID[31038949]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 13.0 ug.mL-1 PMID[18603435]

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 NPC223185 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
0.7234 Intermediate Similarity NPC115207
0.7234 Intermediate Similarity NPC158079
0.7234 Intermediate Similarity NPC228346
0.7234 Intermediate Similarity NPC40432
0.7234 Intermediate Similarity NPC161557
0.68 Remote Similarity NPC308976
0.6667 Remote Similarity NPC126409
0.6667 Remote Similarity NPC99572
0.6667 Remote Similarity NPC610778
0.6604 Remote Similarity NPC27843
0.6604 Remote Similarity NPC7171
0.6429 Remote Similarity NPC478055
0.6296 Remote Similarity NPC478955
0.6296 Remote Similarity NPC478700
0.6034 Remote Similarity NPC88640
0.6034 Remote Similarity NPC101153
0.6034 Remote Similarity NPC193666
0.6034 Remote Similarity NPC123526
0.6034 Remote Similarity NPC608725
0.5862 Remote Similarity NPC483653
0.5849 Remote Similarity NPC147379
0.5849 Remote Similarity NPC469480
0.5806 Remote Similarity NPC125570
0.5738 Remote Similarity NPC67247
0.5577 Remote Similarity NPC142985
0.549 Remote Similarity NPC282703
0.549 Remote Similarity NPC184733
0.549 Remote Similarity NPC128208
0.549 Remote Similarity NPC129570
0.549 Remote Similarity NPC63238
0.549 Remote Similarity NPC602603
0.5469 Remote Similarity NPC265154
0.541 Remote Similarity NPC610652
0.5333 Remote Similarity NPC471942
0.5303 Remote Similarity NPC281780
0.5283 Remote Similarity NPC242807
0.5283 Remote Similarity NPC153739
0.5246 Remote Similarity NPC272
0.5246 Remote Similarity NPC187998
0.5246 Remote Similarity NPC77040
0.5246 Remote Similarity NPC257582
0.5246 Remote Similarity NPC241522
0.5246 Remote Similarity NPC485398
0.5167 Remote Similarity NPC181049
0.5152 Remote Similarity NPC487682
0.5098 Remote Similarity NPC141765
0.5098 Remote Similarity NPC34103
0.5088 Remote Similarity NPC11258
0.5088 Remote Similarity NPC21867
0.5088 Remote Similarity NPC487683
0.5088 Remote Similarity NPC45774
0.5088 Remote Similarity NPC74914
0.5079 Remote Similarity NPC282833
0.5079 Remote Similarity NPC145144
0.5075 Remote Similarity NPC267091

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC223185 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