Natural Product: NPC23336

Natural Product IDNPC23336
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 WMPUHRROBOWDAU-XAAFQQQXSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 102117084
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0001392] Lignans, neolignans and related compounds
      • [CHEMONTID:0003425] Aryltetralin 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 WMPUHRROBOWDAU-XAAFQQQXSA-N
Standard InCHI InChI=1S/C21H22O5/c1-11-4-13-5-16-17(24-9-23-16)8-15(13)20(12(11)2)14-6-18(22-3)21-19(7-14)25-10-26-21/h5-8,11-12,20H,4,9-10H2,1-3H3/t11-,12+,20-/m1/s1
SMILES C[C@@H]1Cc2cc3c(cc2[C@H]([C@H]1C)c1cc(c2c(c1)OCO2)OC)OCO3

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   354.15 Volume:   357.122
?
Van der Waals volume.
Dense:   0.992 LogP:   4.429
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.855
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.428
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   25.0
TPSA:   46.15
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   0.0 Rings:   5.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.812 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.619 Fsp3:   0.429
MCE-18:   88.4
?
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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.639 Fluc inhibitor:   0.648
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.437
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.015
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.306 Promiscuous compounds:   0.293

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.956 MDCK Permeability:   -4.708
Pgp-inhibitor:   0.219 Pgp-substrate:   0.011
PAMPA:   0.013
?
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%):   0.011 30% Bioavailability (F30%):   0.0
50% Bioavailability (F50%):   0.101

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.993 MRP1:   0.98
Plasma Protein Binding (PPB):   96.797% Volume Distribution (VD):   0.289
Fu: 3.995%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.848
OATP1B3 inhibitor:   0.466 BCRP inhibitor:   0.004
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.999 CYP1A2-substrate:   0.957
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.994
CYP2C9-inhibitor:   0.052 CYP2C9-substrate:   1.0
CYP2D6-inhibitor:   0.025 CYP2D6-substrate:   1.0
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.003 CYP2C8-inhibitor:   0.492
HLM stability:   0.052
?
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):  4.721 Half-life (T1/2):  0.659

ADMET: Toxicity

hERG Blockers:  0.329 hERG Blockers (10um):  0.565
Human Hepatotoxicity (H-HT):  0.798 Drug-induced Liver Injury (DILI):  0.955
AMES Toxicity:  0.632 Rat Oral Acute Toxicity:  0.557
Maximum Recommended Daily Dose:  0.857 Skin Sensitization:  0.267
Carcinogencity:  0.856 Eye Corrosion:  0.0
Eye Irritation:  0.43 Respiratory Toxicity:  0.911
Drug-induced Neurotoxicity:  0.803 Ototoxicity:  0.618
Hematotoxicity:  0.762 Drug-induced Nephrotoxicity:  0.665
Genotoxicity:  0.947 RPMI-8226 Immunitoxicity:  0.263
A549 Cytotoxicity:  0.71 Hek293 Cytotoxicity:  0.788
BCF:   2.29
?
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:   4.382
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.264
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.488
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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
NPO8247 Austrobaileya scandens Species Austrobaileyaceae Eukaryota n.a. n.a. n.a. PMID[27214307]
NPO8247 Austrobaileya scandens Species Austrobaileyaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8247 Austrobaileya scandens Species Austrobaileyaceae 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
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 2062.0 nM PMID[27214307]

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 NPC23336 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
0.9091 High Similarity NPC480480
0.74 Intermediate Similarity NPC17348
0.7143 Intermediate Similarity NPC177167
0.6727 Remote Similarity NPC191231
0.6545 Remote Similarity NPC227002
0.6207 Remote Similarity NPC262455
0.6207 Remote Similarity NPC177476
0.62 Remote Similarity NPC601068
0.5763 Remote Similarity NPC80230
0.5763 Remote Similarity NPC480476
0.5763 Remote Similarity NPC104024
0.5763 Remote Similarity NPC101755
0.5763 Remote Similarity NPC304687
0.5763 Remote Similarity NPC65574
0.566 Remote Similarity NPC56091
0.5091 Remote Similarity NPC218841

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC23336 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