Natural Product: NPC228771

Natural Product IDNPC228771
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (8R,7'r,8R)-5-Hydroxy-4,3',4'-Trimethoxy-2,7'-Cyclolignan
IUPAC Name (5R,6R,7R)-5-(3,4-dimethoxyphenyl)-3-methoxy-6,7-dimethyl-5,6,7,8-tetrahydronaphthalen-2-ol
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL564817
PubChem CID 45269248
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 PLNZSVOTOMAFQW-SQHYZVFZSA-N
Standard InCHI InChI=1S/C21H26O4/c1-12-8-15-9-17(22)19(24-4)11-16(15)21(13(12)2)14-6-7-18(23-3)20(10-14)25-5/h6-7,9-13,21-22H,8H2,1-5H3/t12-,13-,21-/m1/s1
SMILES COc1cc(ccc1OC)[C@H]1[C@H](C)[C@H](C)Cc2c1cc(OC)c(c2)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   342.18 Volume:   365.445
?
Van der Waals volume.
Dense:   0.936 LogP:   3.701
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.327
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.561
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The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   17.0
TPSA:   47.92
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   1.0 Rings:   3.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.896 GASA:   1.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.262 Fsp3:   0.429
MCE-18:   62.067
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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:   Accepted GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   1 PAINS Alert:   0
Colloidal aggregators:   0.308 Fluc inhibitor:   0.57
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.476
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.009
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.341 Promiscuous compounds:   0.131

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.108 MDCK Permeability:   -4.774
Pgp-inhibitor:   0.746 Pgp-substrate:   0.143
PAMPA:   0.004
?
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%):   0.114 30% Bioavailability (F30%):   0.042
50% Bioavailability (F50%):   0.597

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.047 MRP1:   0.987
Plasma Protein Binding (PPB):   87.876% Volume Distribution (VD):   0.017
Fu: 11.188%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.997
OATP1B3 inhibitor:   0.987 BCRP inhibitor:   0.452
BSEP inhibitor:   0.998

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.03
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.999
CYP2C9-inhibitor:   0.005 CYP2C9-substrate:   0.984
CYP2D6-inhibitor:   0.013 CYP2D6-substrate:   0.869
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.657
?
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):  7.906 Half-life (T1/2):  1.521

ADMET: Toxicity

hERG Blockers:  0.181 hERG Blockers (10um):  0.53
Human Hepatotoxicity (H-HT):  0.659 Drug-induced Liver Injury (DILI):  0.78
AMES Toxicity:  0.469 Rat Oral Acute Toxicity:  0.313
Maximum Recommended Daily Dose:  0.532 Skin Sensitization:  0.37
Carcinogencity:  0.572 Eye Corrosion:  0.018
Eye Irritation:  0.842 Respiratory Toxicity:  0.861
Drug-induced Neurotoxicity:  0.486 Ototoxicity:  0.65
Hematotoxicity:  0.572 Drug-induced Nephrotoxicity:  0.675
Genotoxicity:  0.103 RPMI-8226 Immunitoxicity:  0.153
A549 Cytotoxicity:  0.56 Hek293 Cytotoxicity:  0.61
BCF:   1.921
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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:   4.17
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.603
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.897
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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
NPO7850 Schisandra propinqua Species Schisandraceae Eukaryota n.a. stem n.a. DOI[10.1002/cjoc.20010190319]
NPO7850 Schisandra propinqua Species Schisandraceae Eukaryota n.a. stem n.a. DOI[10.1016/j.tet.2008.10.079]
NPO7850 Schisandra propinqua Species Schisandraceae Eukaryota n.a. stem n.a. PMID[11395273]
NPO7850 Schisandra propinqua Species Schisandraceae Eukaryota n.a. stem n.a. PMID[18536373]
NPO7850 Schisandra propinqua Species Schisandraceae Eukaryota aerial parts Erlang Mountain area of Sichuan Province, China 2007-SEP PMID[19413342]
NPO7850 Schisandra propinqua Species Schisandraceae Eukaryota n.a. n.a. n.a. PMID[20681569]
NPO7850 Schisandra propinqua Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7374 Seseli montanum Species Apiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7850 Schisandra propinqua Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO7374 Seseli montanum Species Apiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7850 Schisandra propinqua Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11167 Prunus ssiori Species Rosaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9834 Veronica austriaca Species Plantaginaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6903 Lecanora straminea Species Lecanoraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7128 Cynthia savignyi n.a. n.a. n.a. 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
NPT1452 Cell line C8166 Homo sapiens CC50 = 30000.0 nM PMID[19413342]
NPT24 Organism Human immunodeficiency virus 1 Human immunodeficiency virus 1 EC50 = 4500.0 nM PMID[19413342]
NPT2 Others Unspecified n.a. Ratio CC50/EC50 = 6.7 n.a. PMID[19413342]

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 NPC228771 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
0.7292 Intermediate Similarity NPC601068
0.6604 Remote Similarity NPC266705
0.6604 Remote Similarity NPC29008
0.6545 Remote Similarity NPC141817
0.6545 Remote Similarity NPC229218
0.6481 Remote Similarity NPC17348
0.6111 Remote Similarity NPC14224
0.6034 Remote Similarity NPC227002
0.5789 Remote Similarity NPC161958
0.5636 Remote Similarity NPC177167
0.5294 Remote Similarity NPC474040
0.5254 Remote Similarity NPC176030
0.5254 Remote Similarity NPC313081
0.5091 Remote Similarity NPC227217
0.5091 Remote Similarity NPC117780

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC228771 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