Natural Product: NPC185908

Natural Product IDNPC185908
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (-)-Clusin
IUPAC Name (3R,4R)-4-(1,3-benzodioxol-5-ylmethyl)-3-[(3,4,5-trimethoxyphenyl)methyl]oxolan-2-ol
Synonyms (-)-Clusin
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL479701
PubChem CID 44575398
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:0001968] Dibenzylbutyrolactols

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 SOCNBZCAGNYAED-OKFXBHNASA-N
Standard InCHI InChI=1S/C22H26O7/c1-24-19-9-14(10-20(25-2)21(19)26-3)7-16-15(11-27-22(16)23)6-13-4-5-17-18(8-13)29-12-28-17/h4-5,8-10,15-16,22-23H,6-7,11-12H2,1-3H3/t15-,16+,22?/m0/s1
SMILES COc1cc(C[C@@H]2[C@@H](Cc3ccc4c(c3)OCO4)COC2O)cc(c1OC)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   402.17 Volume:   400.555
?
Van der Waals volume.
Dense:   1.004 LogP:   2.432
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.524
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.821
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   7.0 Rigid Bonds:   21.0
TPSA:   75.61
?
Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   1.0 Rings:   4.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.763 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.511 Fsp3:   0.455
MCE-18:   72.875
?
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:   0.119 Fluc inhibitor:   0.197
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.041
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.22
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.058 Promiscuous compounds:   0.257

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.794 MDCK Permeability:   -4.711
Pgp-inhibitor:   0.615 Pgp-substrate:   0.08
PAMPA:   0.175
?
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%):   0.106 30% Bioavailability (F30%):   0.001
50% Bioavailability (F50%):   0.31

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.978 MRP1:   0.974
Plasma Protein Binding (PPB):   96.096% Volume Distribution (VD):   0.021
Fu: 4.431%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.901
OATP1B3 inhibitor:   0.772 BCRP inhibitor:   0.016
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.529 CYP1A2-substrate:   0.239
CYP2C19-inhibitor:   0.999 CYP2C19-substrate:   0.85
CYP2C9-inhibitor:   0.857 CYP2C9-substrate:   0.928
CYP2D6-inhibitor:   0.895 CYP2D6-substrate:   1.0
CYP3A4-inhibitor:   0.998 CYP3A4-substrate:   0.998
CYP2B6-substrate:   0.071 CYP2C8-inhibitor:   0.133
HLM stability:   0.028
?
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):  4.235 Half-life (T1/2):  1.451

ADMET: Toxicity

hERG Blockers:  0.462 hERG Blockers (10um):  0.644
Human Hepatotoxicity (H-HT):  0.863 Drug-induced Liver Injury (DILI):  0.967
AMES Toxicity:  0.691 Rat Oral Acute Toxicity:  0.446
Maximum Recommended Daily Dose:  0.642 Skin Sensitization:  0.405
Carcinogencity:  0.528 Eye Corrosion:  0.001
Eye Irritation:  0.562 Respiratory Toxicity:  0.677
Drug-induced Neurotoxicity:  0.886 Ototoxicity:  0.803
Hematotoxicity:  0.488 Drug-induced Nephrotoxicity:  0.756
Genotoxicity:  0.779 RPMI-8226 Immunitoxicity:  0.22
A549 Cytotoxicity:  0.373 Hek293 Cytotoxicity:  0.602
BCF:   1.511
?
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:   3.786
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.684
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.536
?
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
NPO11169 Piper cubeba Species Piperaceae Eukaryota n.a. n.a. n.a. PMID[15679319]
NPO11169 Piper cubeba Species Piperaceae Eukaryota n.a. n.a. n.a. PMID[31096694]
NPO11169 Piper cubeba Species Piperaceae Eukaryota n.a. n.a. n.a. Database[Article]
NPO11169 Piper cubeba Species Piperaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11169 Piper cubeba Species Piperaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO11169 Piper cubeba Species Piperaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO11169 Piper cubeba Species Piperaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]

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
NPT109 Individual protein Cytochrome P450 3A4 Homo sapiens IC50 = 830.0 nM PMID[15679319]
NPT110 Individual protein Cytochrome P450 2D6 Homo sapiens IC50 > 100000.0 nM PMID[15679319]
NPT109 Individual protein Cytochrome P450 3A4 Homo sapiens Ki = 82.0 nM PMID[16248836]
NPT109 Individual protein Cytochrome P450 3A4 Homo sapiens Kinact = 0.253 min-1 PMID[16248836]

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 NPC185908 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 NPC482891
0.875 High Similarity NPC171550
0.875 High Similarity NPC134764
0.82 Intermediate Similarity NPC283949
0.7708 Intermediate Similarity NPC236522
0.76 Intermediate Similarity NPC482890
0.7593 Intermediate Similarity NPC226547
0.7586 Intermediate Similarity NPC169973
0.7115 Intermediate Similarity NPC192255
0.6852 Remote Similarity NPC143895
0.6415 Remote Similarity NPC196937
0.6379 Remote Similarity NPC176586
0.6379 Remote Similarity NPC210354
0.6032 Remote Similarity NPC56184
0.6 Remote Similarity NPC191158
0.6 Remote Similarity NPC177644
0.5962 Remote Similarity NPC600801
0.5741 Remote Similarity NPC476748
0.569 Remote Similarity NPC173308
0.569 Remote Similarity NPC181079
0.5614 Remote Similarity NPC474288
0.5536 Remote Similarity NPC11453
0.55 Remote Similarity NPC205915
0.5424 Remote Similarity NPC158737
0.5385 Remote Similarity NPC145569
0.5345 Remote Similarity NPC110958
0.5345 Remote Similarity NPC19890
0.5323 Remote Similarity NPC18576
0.5283 Remote Similarity NPC40352
0.5283 Remote Similarity NPC213711
0.5238 Remote Similarity NPC47181
0.5185 Remote Similarity NPC344161
0.5167 Remote Similarity NPC40237
0.5075 Remote Similarity NPC487679
0.5075 Remote Similarity NPC487678

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC185908 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