Natural Product: NPC13780

Natural Product IDNPC13780
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 JJBONXYTPRSQOP-UONOGXRCSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 11782821
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 JJBONXYTPRSQOP-UONOGXRCSA-N
Standard InCHI InChI=1S/C19H18O6/c20-15-3-1-11(7-16(15)21)5-13-9-23-19(22)14(13)6-12-2-4-17-18(8-12)25-10-24-17/h1-4,7-8,13-14,20-21H,5-6,9-10H2/t13-,14+/m0/s1
SMILES c1cc(c(cc1C[C@H]1COC(=O)[C@@H]1Cc1ccc2c(c1)OCO2)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   342.11 Volume:   337.24
?
Van der Waals volume.
Dense:   1.014 LogP:   2.088
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.045
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.604
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   22.0
TPSA:   85.22
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   2.0 Rings:   4.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.656 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.265 Fsp3:   0.316
MCE-18:   69.72
?
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:   1
Colloidal aggregators:   0.541 Fluc inhibitor:   0.723
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.034
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.194
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.312 Promiscuous compounds:   0.587

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.944 MDCK Permeability:   -4.688
Pgp-inhibitor:   0.123 Pgp-substrate:   0.013
PAMPA:   0.261
?
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%):   0.902 30% Bioavailability (F30%):   0.242
50% Bioavailability (F50%):   0.875

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.015 MRP1:   0.612
Plasma Protein Binding (PPB):   97.659% Volume Distribution (VD):   -0.463
Fu: 2.743%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.981
OATP1B3 inhibitor:   0.844 BCRP inhibitor:   0.006
BSEP inhibitor:   0.997

ADMET: Metabolism

CYP1A2-inhibitor:   0.005 CYP1A2-substrate:   0.419
CYP2C19-inhibitor:   0.986 CYP2C19-substrate:   0.85
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.696
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   1.0
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.99
HLM stability:   0.906
?
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):  5.972 Half-life (T1/2):  1.936

ADMET: Toxicity

hERG Blockers:  0.153 hERG Blockers (10um):  0.706
Human Hepatotoxicity (H-HT):  0.933 Drug-induced Liver Injury (DILI):  0.976
AMES Toxicity:  0.852 Rat Oral Acute Toxicity:  0.3
Maximum Recommended Daily Dose:  0.664 Skin Sensitization:  0.988
Carcinogencity:  0.733 Eye Corrosion:  0.009
Eye Irritation:  0.97 Respiratory Toxicity:  0.161
Drug-induced Neurotoxicity:  0.348 Ototoxicity:  0.762
Hematotoxicity:  0.379 Drug-induced Nephrotoxicity:  0.601
Genotoxicity:  0.998 RPMI-8226 Immunitoxicity:  0.066
A549 Cytotoxicity:  0.745 Hek293 Cytotoxicity:  0.513
BCF:   1.416
?
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:   4.16
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.454
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.03
?
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
NPO28392 Macrosiphum liriodendri Species Aphididae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28510 Aspergillus pseudodeflectus Species Aspergillaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28218 Asplenium adiantum-nigrum Species Aspleniaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28036 Distemonanthus benthamianus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28036 Distemonanthus benthamianus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO28036 Distemonanthus benthamianus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO28036 Distemonanthus benthamianus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO28218 Asplenium adiantum-nigrum Species Aspleniaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28392 Macrosiphum liriodendri Species Aphididae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28510 Aspergillus pseudodeflectus Species Aspergillaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28036 Distemonanthus benthamianus Species Fabaceae 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 NPC13780 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
0.8036 Intermediate Similarity NPC5310
0.7885 Intermediate Similarity NPC110958
0.7885 Intermediate Similarity NPC19890
0.7667 Intermediate Similarity NPC282291
0.7667 Intermediate Similarity NPC166137
0.7333 Intermediate Similarity NPC145569
0.7321 Intermediate Similarity NPC205915
0.7069 Intermediate Similarity NPC176586
0.7069 Intermediate Similarity NPC210354
0.6949 Remote Similarity NPC191158
0.6949 Remote Similarity NPC177644
0.6462 Remote Similarity NPC216223
0.629 Remote Similarity NPC300776
0.629 Remote Similarity NPC176814
0.629 Remote Similarity NPC4982
0.629 Remote Similarity NPC606629
0.6212 Remote Similarity NPC174512
0.6182 Remote Similarity NPC476748
0.6071 Remote Similarity NPC223807
0.5938 Remote Similarity NPC293757
0.5938 Remote Similarity NPC668
0.5932 Remote Similarity NPC92693
0.5909 Remote Similarity NPC487679
0.5909 Remote Similarity NPC487678
0.5833 Remote Similarity NPC68779
0.5833 Remote Similarity NPC108598
0.5833 Remote Similarity NPC40237
0.5781 Remote Similarity NPC106920
0.5781 Remote Similarity NPC15811
0.5781 Remote Similarity NPC3982
0.5714 Remote Similarity NPC478703
0.5714 Remote Similarity NPC478704
0.5667 Remote Similarity NPC211386
0.5574 Remote Similarity NPC143895
0.5536 Remote Similarity NPC600801
0.5517 Remote Similarity NPC325295
0.5517 Remote Similarity NPC76308
0.5469 Remote Similarity NPC273657
0.5441 Remote Similarity NPC56184
0.5172 Remote Similarity NPC72796
0.5167 Remote Similarity NPC249788
0.5161 Remote Similarity NPC171550
0.5161 Remote Similarity NPC134764
0.5143 Remote Similarity NPC169973
0.5139 Remote Similarity NPC478705
0.5079 Remote Similarity NPC158737

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC13780 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