Natural Product: NPC209229

Natural Product IDNPC209229
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Caruilignan C
IUPAC Name (3R,3aR,6aR)-3-(3,4,5-trimethoxyphenyl)-3,3a,4,6a-tetrahydro-1H-furo[3,4-c]furan-6-one
Synonyms Caruilignan C
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL508457
PubChem CID 10685181
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 BYXOLWYJKZALLQ-KWBADKCTSA-N
Standard InCHI InChI=1S/C15H18O6/c1-17-11-4-8(5-12(18-2)14(11)19-3)13-9-6-21-15(16)10(9)7-20-13/h4-5,9-10,13H,6-7H2,1-3H3/t9-,10-,13-/m0/s1
SMILES COc1cc(cc(c1OC)OC)[C@@H]1OC[C@H]2[C@@H]1COC2=O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   294.11 Volume:   284.522
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Van der Waals volume.
Dense:   1.034 LogP:   1.161
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.572
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.418
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The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   16.0
TPSA:   63.22
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Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   0.0 Rings:   3.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.786 GASA:   1.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.507 Fsp3:   0.533
MCE-18:   58.391
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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:   0.278 Fluc inhibitor:   0.274
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.035
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.028
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.34 Promiscuous compounds:   0.286

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.852 MDCK Permeability:   -4.742
Pgp-inhibitor:   0.06 Pgp-substrate:   0.015
PAMPA:   0.067
?
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%):   0.155 30% Bioavailability (F30%):   0.018
50% Bioavailability (F50%):   0.385

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.797 MRP1:   0.995
Plasma Protein Binding (PPB):   66.864% Volume Distribution (VD):   -0.14
Fu: 28.459%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.252
OATP1B3 inhibitor:   0.609 BCRP inhibitor:   0.013
BSEP inhibitor:   0.899

ADMET: Metabolism

CYP1A2-inhibitor:   0.718 CYP1A2-substrate:   0.167
CYP2C19-inhibitor:   0.983 CYP2C19-substrate:   0.002
CYP2C9-inhibitor:   0.064 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.09
CYP3A4-inhibitor:   0.999 CYP3A4-substrate:   0.458
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.634
HLM stability:   0.185
?
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):  4.126 Half-life (T1/2):  2.078

ADMET: Toxicity

hERG Blockers:  0.074 hERG Blockers (10um):  0.385
Human Hepatotoxicity (H-HT):  0.809 Drug-induced Liver Injury (DILI):  0.981
AMES Toxicity:  0.613 Rat Oral Acute Toxicity:  0.426
Maximum Recommended Daily Dose:  0.355 Skin Sensitization:  0.996
Carcinogencity:  0.719 Eye Corrosion:  0.334
Eye Irritation:  0.943 Respiratory Toxicity:  0.782
Drug-induced Neurotoxicity:  0.757 Ototoxicity:  0.559
Hematotoxicity:  0.754 Drug-induced Nephrotoxicity:  0.888
Genotoxicity:  0.818 RPMI-8226 Immunitoxicity:  0.139
A549 Cytotoxicity:  0.614 Hek293 Cytotoxicity:  0.392
BCF:   0.768
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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:   3.16
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.238
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.719
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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
NPO26589 Artemisia annua L. Strain Asteraceae Eukaryota n.a. n.a. n.a. PMID[ 21030913]
NPO26589 Artemisia annua L. Strain Asteraceae Eukaryota n.a. leaf n.a. DOI[10.1007/s11418-006-0112-9]
NPO26589 Artemisia annua L. Strain Asteraceae Eukaryota n.a. flower n.a. DOI[10.1007/s11418-006-0112-9]
NPO26589 Artemisia annua L. Strain Asteraceae Eukaryota n.a. stem n.a. DOI[10.1007/s11418-006-0112-9]
NPO26589 Artemisia annua L. Strain Asteraceae Eukaryota n.a. n.a. n.a. PMID[6387056]
NPO10506 Artemisia apiacea Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26589 Artemisia annua L. Strain Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26589 Artemisia annua L. Strain Asteraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO10506 Artemisia apiacea Species Asteraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO26589 Artemisia annua L. Strain Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO10506 Artemisia apiacea Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO26589 Artemisia annua L. Strain Asteraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO10506 Artemisia apiacea Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO10506 Artemisia apiacea Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO26589 Artemisia annua L. Strain Asteraceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO26589 Artemisia annua L. Strain Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10506 Artemisia apiacea 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

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT2 Others Unspecified n.a. IC50 > 4.0 ug.mL-1 PMID[12141878]

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 NPC209229 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
0.7727 Intermediate Similarity NPC488505
0.7174 Intermediate Similarity NPC27159
0.7174 Intermediate Similarity NPC186220
0.675 Remote Similarity NPC281864
0.675 Remote Similarity NPC328682
0.675 Remote Similarity NPC54321
0.6531 Remote Similarity NPC14022
0.6531 Remote Similarity NPC601703
0.6275 Remote Similarity NPC610778
0.6087 Remote Similarity NPC222127
0.6087 Remote Similarity NPC82862
0.6 Remote Similarity NPC473092
0.6 Remote Similarity NPC473093
0.6 Remote Similarity NPC8050
0.5781 Remote Similarity NPC473236
0.5745 Remote Similarity NPC148893
0.5745 Remote Similarity NPC25333
0.5745 Remote Similarity NPC49235
0.5625 Remote Similarity NPC165155
0.5625 Remote Similarity NPC24490
0.549 Remote Similarity NPC189474
0.5217 Remote Similarity NPC121783
0.5217 Remote Similarity NPC34902
0.5217 Remote Similarity NPC18449

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC209229 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