Natural Product: NPC109493

Natural Product IDNPC109493
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 AJJJAWBHPZAOKJ-GAJHUEQPSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 14630580
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 AJJJAWBHPZAOKJ-GAJHUEQPSA-N
Standard InCHI InChI=1S/C23H24O8/c1-14(24)31-23(11-16-5-6-18(26-2)20(10-16)27-3)17(12-28-22(23)25)8-15-4-7-19-21(9-15)30-13-29-19/h4-7,9-10,17H,8,11-13H2,1-3H3/t17-,23+/m0/s1
SMILES CC(=O)O[C@]1(Cc2ccc(c(c2)OC)OC)[C@@H](Cc2ccc3c(c2)OCO3)COC1=O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   428.15 Volume:   421.368
?
Van der Waals volume.
Dense:   1.016 LogP:   1.966
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.221
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.313
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   8.0 Rigid Bonds:   23.0
TPSA:   89.52
?
Topological Polar Surface Area.
 H-Bond Acceptor:   8.0
H-Bond Donor:   0.0 Rings:   4.0
Heavy Atoms:   8.0

MedChem Properties

QED Drug-Likeness Score:   0.622 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.546 Fsp3:   0.391
MCE-18:   78.0
?
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:   0.12 Fluc inhibitor:   0.157
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.02
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.449
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.287 Promiscuous compounds:   0.123

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.912 MDCK Permeability:   -4.664
Pgp-inhibitor:   0.992 Pgp-substrate:   0.026
PAMPA:   0.048
?
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%):   0.335 30% Bioavailability (F30%):   0.007
50% Bioavailability (F50%):   0.541

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.055 MRP1:   0.911
Plasma Protein Binding (PPB):   97.775% Volume Distribution (VD):   -0.081
Fu: 2.424%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.993
OATP1B3 inhibitor:   0.792 BCRP inhibitor:   0.003
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.998 CYP1A2-substrate:   0.13
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.112
CYP2C9-inhibitor:   0.344 CYP2C9-substrate:   0.162
CYP2D6-inhibitor:   0.001 CYP2D6-substrate:   1.0
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   0.999
CYP2B6-substrate:   0.47 CYP2C8-inhibitor:   0.699
HLM stability:   0.793
?
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):  2.984 Half-life (T1/2):  1.265

ADMET: Toxicity

hERG Blockers:  0.171 hERG Blockers (10um):  0.549
Human Hepatotoxicity (H-HT):  0.791 Drug-induced Liver Injury (DILI):  0.883
AMES Toxicity:  0.918 Rat Oral Acute Toxicity:  0.465
Maximum Recommended Daily Dose:  0.613 Skin Sensitization:  0.947
Carcinogencity:  0.934 Eye Corrosion:  0.008
Eye Irritation:  0.57 Respiratory Toxicity:  0.337
Drug-induced Neurotoxicity:  0.899 Ototoxicity:  0.494
Hematotoxicity:  0.709 Drug-induced Nephrotoxicity:  0.944
Genotoxicity:  0.988 RPMI-8226 Immunitoxicity:  0.23
A549 Cytotoxicity:  0.323 Hek293 Cytotoxicity:  0.514
BCF:   1.117
?
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:   4.091
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.34
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.001
?
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
NPO12176 Streptomyces olivaceus Species Streptomycetaceae Bacteria n.a. n.a. n.a. PMID[11376004]
NPO12176 Streptomyces olivaceus Species Streptomycetaceae Bacteria n.a. n.a. n.a. PMID[1367428]
NPO2291 Saussurea pulchella Species Asteraceae Eukaryota aerial parts n.a. n.a. PMID[18314958]
NPO11237 Bupleurum salicifolium Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[24242108]
NPO12422 Pinus massoniana Species Pinaceae Eukaryota n.a. n.a. n.a. PMID[32100544]
NPO11237 Bupleurum salicifolium Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[7964800]
NPO12176 Streptomyces olivaceus Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[Article]
NPO16792 Nocardia pseudobrasiliensis Species Nocardiaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO12422 Pinus massoniana Species Pinaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2291 Saussurea pulchella Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7327 Aeromonas hydrophila Species Aeromonadaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO8414 Crella incrustans Species Crellidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11400 Aster ptarmicoides Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2582 Plagiomnium undulatum Species Mniaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16343 Galium album Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7991 Lactarius vellereus Species Russulaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12176 Streptomyces olivaceus Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO4033 Corydalis gigantea Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO12422 Pinus massoniana Species Pinaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO2291 Saussurea pulchella Species Asteraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO7991 Lactarius vellereus Species Russulaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO12874 Sedum cepaea Species Crassulaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO11400 Aster ptarmicoides Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO12422 Pinus massoniana Species Pinaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO2291 Saussurea pulchella Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO6669 Dysosma delavayi Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO4033 Corydalis gigantea Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO7991 Lactarius vellereus Species Russulaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO4033 Corydalis gigantea Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO12422 Pinus massoniana Species Pinaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO2291 Saussurea pulchella Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO12422 Pinus massoniana Species Pinaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO10719 Centrosema haitense Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7653 Mosla japonica Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9496 Gomphostemma crinitum Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9018 Millettia rubiginosa Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11400 Aster ptarmicoides Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11237 Bupleurum salicifolium Species Apiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4970 Torricellia tiliifolia Species Torricelliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3017 Artemisia caucasica Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7991 Lactarius vellereus Species Russulaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2291 Saussurea pulchella Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6669 Dysosma delavayi Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12176 Streptomyces olivaceus Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO16343 Galium album Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16792 Nocardia pseudobrasiliensis Species Nocardiaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO7327 Aeromonas hydrophila Species Aeromonadaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO10354 Urbanodendron verrucosum Species Lauraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1460 Rubus phoenicolasius Species Rosaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20210 Lophozia floerkei Species Scapaniaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17456 Echinochloa esculenta Species Poaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4033 Corydalis gigantea Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3614 Echinopepon bigelovii Species Cucurbitaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12659 Hopea brevipetiolaris Species Dipterocarpaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6235 Exobasidium vaccinii Species Exobasidiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12874 Sedum cepaea Species Crassulaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2582 Plagiomnium undulatum Species Mniaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9648 Maharanga bicolor Species Boraginaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12422 Pinus massoniana Species Pinaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10560 Adenia fruticosa Species Passifloraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1164 Osteospermum hyoseroides Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8414 Crella incrustans Species Crellidae 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 NPC109493 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
0.6 Remote Similarity NPC476748
0.5932 Remote Similarity NPC143895
0.5741 Remote Similarity NPC344161
0.5738 Remote Similarity NPC205915
0.5294 Remote Similarity NPC487679
0.5294 Remote Similarity NPC487678
0.5088 Remote Similarity NPC600801
0.5082 Remote Similarity NPC192255
0.5082 Remote Similarity NPC110958
0.5082 Remote Similarity NPC19890
0.5077 Remote Similarity NPC176586
0.5077 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 NPC109493 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