Natural Product: NPC242517

Natural Product IDNPC242517
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 CMJGAYUQSLJSCR-GIDUJCDVSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 5321147
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 CMJGAYUQSLJSCR-GIDUJCDVSA-N
Standard InCHI InChI=1S/C20H16O6/c21-20-15(6-13-2-4-17-19(8-13)26-11-24-17)14(9-22-20)5-12-1-3-16-18(7-12)25-10-23-16/h1-4,6-8,14H,5,9-11H2/b15-6+
SMILES c1cc2c(cc1CC1COC(=O)/C/1=C/c1ccc3c(c1)OCO3)OCO2

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   352.09 Volume:   343.344
?
Van der Waals volume.
Dense:   1.025 LogP:   3.006
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.846
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.179
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   27.0
TPSA:   63.22
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   0.0 Rings:   5.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.625 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.098 Fsp3:   0.25
MCE-18:   79.68
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Accepted GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.883 Fluc inhibitor:   0.839
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.068
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.486
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.305 Promiscuous compounds:   0.006

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.992 MDCK Permeability:   -4.735
Pgp-inhibitor:   0.96 Pgp-substrate:   0.0
PAMPA:   0.11
?
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%):   0.028 30% Bioavailability (F30%):   0.0
50% Bioavailability (F50%):   0.075

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.724 MRP1:   0.192
Plasma Protein Binding (PPB):   97.793% Volume Distribution (VD):   0.01
Fu: 3.037%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.851
OATP1B3 inhibitor:   0.898 BCRP inhibitor:   0.0
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.94 CYP1A2-substrate:   0.01
CYP2C19-inhibitor:   0.089 CYP2C19-substrate:   0.003
CYP2C9-inhibitor:   0.007 CYP2C9-substrate:   0.384
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   1.0
CYP3A4-inhibitor:   0.999 CYP3A4-substrate:   0.996
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.0
HLM stability:   0.1
?
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):  2.884 Half-life (T1/2):  0.918

ADMET: Toxicity

hERG Blockers:  0.267 hERG Blockers (10um):  0.502
Human Hepatotoxicity (H-HT):  0.891 Drug-induced Liver Injury (DILI):  0.954
AMES Toxicity:  0.91 Rat Oral Acute Toxicity:  0.667
Maximum Recommended Daily Dose:  0.892 Skin Sensitization:  0.912
Carcinogencity:  0.979 Eye Corrosion:  0.0
Eye Irritation:  0.122 Respiratory Toxicity:  0.233
Drug-induced Neurotoxicity:  0.841 Ototoxicity:  0.75
Hematotoxicity:  0.757 Drug-induced Nephrotoxicity:  0.959
Genotoxicity:  0.998 RPMI-8226 Immunitoxicity:  0.318
A549 Cytotoxicity:  0.415 Hek293 Cytotoxicity:  0.86
BCF:   1.583
?
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:   4.471
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.315
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.72
?
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
NPO3854 Ruta graveolens Species Rutaceae Eukaryota n.a. n.a. n.a. DOI[10.1042/BA20070200]
NPO3854 Ruta graveolens Species Rutaceae Eukaryota leaves n.a. n.a. PMID[12568545]
NPO3854 Ruta graveolens Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[19191562]
NPO1087 Pterocarpus santalinus Species Fabaceae Eukaryota n.a. heartwood n.a. PMID[21488654]
NPO1087 Pterocarpus santalinus Species Fabaceae Eukaryota Heartwood India n.a. PMID[21488654]
NPO1087 Pterocarpus santalinus Species Fabaceae Eukaryota heartwood n.a. n.a. PMID[21784631]
NPO24241 Taiwania cryptomerioides Species Cupressaceae Eukaryota n.a. twig n.a. PMID[22474975]
NPO30633 Acanthopanax sessiliflorus n.a. n.a. n.a. Fruits n.a. n.a. PMID[22691179]
NPO3854 Ruta graveolens Species Rutaceae Eukaryota Whole Plants n.a. n.a. PMID[28093914]
NPO24241 Taiwania cryptomerioides Species Cupressaceae Eukaryota n.a. n.a. n.a. PMID[31347365]
NPO8500 Acanthopanax gracilistylus Species Araliaceae Eukaryota n.a. n.a. n.a. PMID[32319765]
NPO20275 Juniperus sabina Species Cupressaceae Eukaryota n.a. n.a. n.a. PMID[34203980]
NPO20275 Juniperus sabina Species Cupressaceae Eukaryota n.a. n.a. n.a. PMID[37894884]
NPO24241 Taiwania cryptomerioides Species Cupressaceae Eukaryota n.a. n.a. n.a. PMID[9014350]
NPO3854 Ruta graveolens Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20275 Juniperus sabina Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1087 Pterocarpus santalinus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO22976 Ruta microcarpa Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO30115 Aucklandia lappa n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO24241 Taiwania cryptomerioides Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO30633 Acanthopanax sessiliflorus n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO24241 Taiwania cryptomerioides Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO1087 Pterocarpus santalinus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO20275 Juniperus sabina Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO30633 Acanthopanax sessiliflorus n.a. n.a. n.a. n.a. n.a. n.a. Database[HerDing]
NPO3854 Ruta graveolens Species Rutaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO22976 Ruta microcarpa Species Rutaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO22976 Ruta microcarpa Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO24241 Taiwania cryptomerioides Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO20275 Juniperus sabina Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO3854 Ruta graveolens Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO8500 Acanthopanax gracilistylus Species Araliaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO1087 Pterocarpus santalinus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO30115 Aucklandia lappa n.a. n.a. n.a. n.a. n.a. n.a. Database[TCM_Taiwan]
NPO1087 Pterocarpus santalinus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO20275 Juniperus sabina Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO24241 Taiwania cryptomerioides Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO3854 Ruta graveolens Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO30633 Acanthopanax sessiliflorus n.a. n.a. n.a. n.a. n.a. n.a. Database[TCM_Taiwan]
NPO22976 Ruta microcarpa Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO753 Acanthopanax sessiliflorum n.a. n.a. n.a. n.a. n.a. n.a. Database[TM-MC]
NPO8500 Acanthopanax gracilistylus Species Araliaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO8500 Acanthopanax gracilistylus Species Araliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1087 Pterocarpus santalinus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24241 Taiwania cryptomerioides Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22976 Ruta microcarpa Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20275 Juniperus sabina Species Cupressaceae 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

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 NPC242517 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 NPC230968
1.0 High Similarity NPC102260
0.6094 Remote Similarity NPC32079
0.6038 Remote Similarity NPC476748
0.5714 Remote Similarity NPC474158
0.566 Remote Similarity NPC600801
0.5614 Remote Similarity NPC110958
0.5614 Remote Similarity NPC19890
0.5556 Remote Similarity NPC90431
0.5424 Remote Similarity NPC158737
0.5424 Remote Similarity NPC143895
0.5246 Remote Similarity NPC205915
0.5085 Remote Similarity NPC192255
0.5079 Remote Similarity NPC176586
0.5079 Remote Similarity NPC210354

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC242517 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