Natural Product: NPC72796

Natural Product IDNPC72796
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (-)-Cubebininolide
IUPAC Name (3R,4R)-3,4-bis[(3,4,5-trimethoxyphenyl)methyl]oxolan-2-one
Synonyms (-)-Cubebininolide
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL479314
PubChem CID 13916150
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0001392] Lignans, neolignans and related compounds
      • [CHEMONTID:0003686] Furanoid lignans
        • [CHEMONTID:0001604] Tetrahydrofuran lignans
          • [CHEMONTID:0003424] 9,9'-epoxylignans
            • [CHEMONTID:0001613] Dibenzylbutyrolactone 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 VUNCHONBJWJYID-DLBZAZTESA-N
Standard InCHI InChI=1S/C24H30O8/c1-26-18-9-14(10-19(27-2)22(18)30-5)7-16-13-32-24(25)17(16)8-15-11-20(28-3)23(31-6)21(12-15)29-4/h9-12,16-17H,7-8,13H2,1-6H3/t16-,17+/m0/s1
SMILES COc1c(OC)cc(cc1OC)C[C@H]1C(=O)OC[C@@H]1Cc1cc(OC)c(c(c1)OC)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   446.19 Volume:   449.857
?
Van der Waals volume.
Dense:   0.992 LogP:   1.842
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.227
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.703
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   10.0 Rigid Bonds:   18.0
TPSA:   81.68
?
Topological Polar Surface Area.
 H-Bond Acceptor:   8.0
H-Bond Donor:   0.0 Rings:   3.0
Heavy Atoms:   8.0

MedChem Properties

QED Drug-Likeness Score:   0.514 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.217 Fsp3:   0.458
MCE-18:   63.429
?
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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.111 Fluc inhibitor:   0.067
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.038
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.299
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.325 Promiscuous compounds:   0.229

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.606 MDCK Permeability:   -4.598
Pgp-inhibitor:   0.539 Pgp-substrate:   0.06
PAMPA:   0.011
?
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):   0.001
20% Bioavailability (F20%):   0.372 30% Bioavailability (F30%):   0.052
50% Bioavailability (F50%):   0.629

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.217 MRP1:   0.995
Plasma Protein Binding (PPB):   95.038% Volume Distribution (VD):   -0.396
Fu: 5.346%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.978
OATP1B3 inhibitor:   0.947 BCRP inhibitor:   0.023
BSEP inhibitor:   0.999

ADMET: Metabolism

CYP1A2-inhibitor:   0.001 CYP1A2-substrate:   0.275
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.999
CYP2C9-inhibitor:   0.002 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.968
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.129
?
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):  5.476 Half-life (T1/2):  1.477

ADMET: Toxicity

hERG Blockers:  0.347 hERG Blockers (10um):  0.661
Human Hepatotoxicity (H-HT):  0.92 Drug-induced Liver Injury (DILI):  0.974
AMES Toxicity:  0.411 Rat Oral Acute Toxicity:  0.669
Maximum Recommended Daily Dose:  0.617 Skin Sensitization:  0.946
Carcinogencity:  0.715 Eye Corrosion:  0.001
Eye Irritation:  0.44 Respiratory Toxicity:  0.71
Drug-induced Neurotoxicity:  0.956 Ototoxicity:  0.84
Hematotoxicity:  0.848 Drug-induced Nephrotoxicity:  0.937
Genotoxicity:  0.956 RPMI-8226 Immunitoxicity:  0.327
A549 Cytotoxicity:  0.535 Hek293 Cytotoxicity:  0.543
BCF:   1.894
?
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:   4.218
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.414
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.801
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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
NPO11169 Piper cubeba Species Piperaceae Eukaryota n.a. n.a. n.a. PMID[15679319]
NPO10449 Arctium lappa Species Asteraceae Eukaryota n.a. fruit n.a. PMID[22396124]
NPO10449 Arctium lappa Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[23501116]
NPO11169 Piper cubeba Species Piperaceae Eukaryota n.a. n.a. n.a. PMID[31096694]
NPO11169 Piper cubeba Species Piperaceae Eukaryota n.a. n.a. n.a. Database[Article]
NPO11169 Piper cubeba Species Piperaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10449 Arctium lappa Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10449 Arctium lappa Species Asteraceae Eukaryota Fruit n.a. n.a. Database[FooDB]
NPO10449 Arctium lappa Species Asteraceae Eukaryota Leaf n.a. n.a. Database[FooDB]
NPO10449 Arctium lappa Species Asteraceae Eukaryota Root n.a. n.a. Database[FooDB]
NPO10449 Arctium lappa Species Asteraceae Eukaryota Seed n.a. n.a. Database[FooDB]
NPO10449 Arctium lappa Species Asteraceae Eukaryota n.a. n.a. Database[FooDB]
NPO11169 Piper cubeba Species Piperaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO10449 Arctium lappa Species Asteraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO10449 Arctium lappa Species Asteraceae Eukaryota n.a. n.a. Database[Phenol-Explorer]
NPO10449 Arctium lappa Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO11169 Piper cubeba Species Piperaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO10449 Arctium lappa Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO11169 Piper cubeba Species Piperaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO10449 Arctium lappa Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO10449 Arctium lappa Species Asteraceae 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
NPT109 Individual protein Cytochrome P450 3A4 Homo sapiens IC50 = 14900.0 nM PMID[15679319]
NPT110 Individual protein Cytochrome P450 2D6 Homo sapiens IC50 > 100000.0 nM PMID[15679319]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference

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 NPC72796 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
0.8571 High Similarity NPC211386
0.8372 Intermediate Similarity NPC40237
0.814 Intermediate Similarity NPC92693
0.766 Intermediate Similarity NPC176586
0.766 Intermediate Similarity NPC210354
0.7619 Intermediate Similarity NPC223807
0.7347 Intermediate Similarity NPC106920
0.7347 Intermediate Similarity NPC15811
0.7143 Intermediate Similarity NPC191158
0.7143 Intermediate Similarity NPC177644
0.6863 Remote Similarity NPC293757
0.6863 Remote Similarity NPC668
0.6531 Remote Similarity NPC205915
0.6383 Remote Similarity NPC110958
0.6383 Remote Similarity NPC19890
0.625 Remote Similarity NPC174512
0.625 Remote Similarity NPC216223
0.6122 Remote Similarity NPC68779
0.6122 Remote Similarity NPC108598
0.6038 Remote Similarity NPC5310
0.6038 Remote Similarity NPC300776
0.6038 Remote Similarity NPC176814
0.6038 Remote Similarity NPC4982
0.6038 Remote Similarity NPC606629
0.6 Remote Similarity NPC145569
0.5962 Remote Similarity NPC273657
0.5957 Remote Similarity NPC11453
0.58 Remote Similarity NPC143895
0.5714 Remote Similarity NPC143092
0.5517 Remote Similarity NPC282291
0.5517 Remote Similarity NPC166137
0.55 Remote Similarity NPC478705
0.5273 Remote Similarity NPC18211
0.5208 Remote Similarity NPC236522
0.5161 Remote Similarity NPC478703
0.5161 Remote Similarity NPC478704
0.5102 Remote Similarity NPC325295
0.5102 Remote Similarity NPC76308
0.5098 Remote Similarity NPC192255
0.5085 Remote Similarity NPC76687
0.5085 Remote Similarity NPC56184
0.5085 Remote Similarity NPC482889

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC72796 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