Natural Product: NPC165155

Natural Product IDNPC165155
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (-)-(7R,7'r,8S,8's)-4'-Hydroxy-3,3',4,5,5'-Pentamethoxy-7,9':7',9-Diepoxylignane
IUPAC Name 4-[(3R,3aS,6R,6aS)-6-(3,4,5-trimethoxyphenyl)-1,3,3a,4,6,6a-hexahydrofuro[3,4-c]furan-3-yl]-2,6-dimethoxyphenol
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1797774
PubChem CID 53356312
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0001392] Lignans, neolignans and related compounds
      • [CHEMONTID:0003686] Furanoid 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 AJMQKDTUOKAQNT-SDVFQCAASA-N
Standard InCHI InChI=1S/C23H28O8/c1-25-16-6-12(7-17(26-2)20(16)24)21-14-10-31-22(15(14)11-30-21)13-8-18(27-3)23(29-5)19(9-13)28-4/h6-9,14-15,21-22,24H,10-11H2,1-5H3/t14-,15-,21+,22+/m1/s1
SMILES COc1cc(cc(c1OC)OC)[C@@H]1OC[C@@H]2[C@H]1CO[C@H]2c1cc(OC)c(c(c1)OC)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   432.18 Volume:   426.641
?
Van der Waals volume.
Dense:   1.013 LogP:   1.424
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.912
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.228
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   7.0 Rigid Bonds:   21.0
TPSA:   84.84
?
Topological Polar Surface Area.
 H-Bond Acceptor:   8.0
H-Bond Donor:   1.0 Rings:   4.0
Heavy Atoms:   8.0

MedChem Properties

QED Drug-Likeness Score:   0.712 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.748 Fsp3:   0.478
MCE-18:   80.471
?
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:   1 PAINS Alert:   0
Colloidal aggregators:   0.316 Fluc inhibitor:   0.268
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.035
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.201
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.263 Promiscuous compounds:   0.532

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.252 MDCK Permeability:   -4.838
Pgp-inhibitor:   0.669 Pgp-substrate:   0.158
PAMPA:   0.001
?
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%):   0.025 30% Bioavailability (F30%):   0.006
50% Bioavailability (F50%):   0.653

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.743 MRP1:   0.997
Plasma Protein Binding (PPB):   83.665% Volume Distribution (VD):   -0.237
Fu: 13.581%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.997
OATP1B3 inhibitor:   0.992 BCRP inhibitor:   0.761
BSEP inhibitor:   0.982

ADMET: Metabolism

CYP1A2-inhibitor:   0.987 CYP1A2-substrate:   0.691
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.478
CYP2C9-inhibitor:   0.014 CYP2C9-substrate:   0.021
CYP2D6-inhibitor:   0.004 CYP2D6-substrate:   0.365
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   0.991
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.898
HLM stability:   0.033
?
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):  7.703 Half-life (T1/2):  2.148

ADMET: Toxicity

hERG Blockers:  0.108 hERG Blockers (10um):  0.467
Human Hepatotoxicity (H-HT):  0.756 Drug-induced Liver Injury (DILI):  0.917
AMES Toxicity:  0.549 Rat Oral Acute Toxicity:  0.357
Maximum Recommended Daily Dose:  0.385 Skin Sensitization:  0.81
Carcinogencity:  0.639 Eye Corrosion:  0.008
Eye Irritation:  0.804 Respiratory Toxicity:  0.464
Drug-induced Neurotoxicity:  0.57 Ototoxicity:  0.377
Hematotoxicity:  0.559 Drug-induced Nephrotoxicity:  0.51
Genotoxicity:  0.507 RPMI-8226 Immunitoxicity:  0.251
A549 Cytotoxicity:  0.351 Hek293 Cytotoxicity:  0.357
BCF:   1.786
?
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:   3.784
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.197
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.407
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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
NPO19192 Sinocalamus affinis Species n.a. n.a. n.a. stem n.a. PMID[21469695]
NPO19192 Sinocalamus affinis Species n.a. n.a. skin-removed stems Pingle Town, Sichuang Province, China 2008-AUG PMID[21469695]
NPO19192 Sinocalamus affinis Species n.a. n.a. n.a. n.a. n.a. PMID[22690646]
NPO19192 Sinocalamus affinis Species n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO19192 Sinocalamus affinis Species 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
NPT2 Others Unspecified n.a. Inhibition < 30.0 % PMID[21469695]

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 NPC165155 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 NPC24490
0.8649 High Similarity NPC141765
0.8649 High Similarity NPC34103
0.8182 Intermediate Similarity NPC185071
0.7838 Intermediate Similarity NPC281864
0.7838 Intermediate Similarity NPC328682
0.7838 Intermediate Similarity NPC54321
0.7111 Intermediate Similarity NPC126409
0.7111 Intermediate Similarity NPC99572
0.6957 Remote Similarity NPC479434
0.6939 Remote Similarity NPC298317
0.6939 Remote Similarity NPC255566
0.6905 Remote Similarity NPC473092
0.6905 Remote Similarity NPC473093
0.6905 Remote Similarity NPC8050
0.6744 Remote Similarity NPC204215
0.6591 Remote Similarity NPC148893
0.6591 Remote Similarity NPC222127
0.6591 Remote Similarity NPC25333
0.6591 Remote Similarity NPC49235
0.6591 Remote Similarity NPC82862
0.6444 Remote Similarity NPC326095
0.6346 Remote Similarity NPC12728
0.625 Remote Similarity NPC27159
0.625 Remote Similarity NPC186220
0.6222 Remote Similarity NPC115207
0.6222 Remote Similarity NPC158079
0.6222 Remote Similarity NPC228346
0.6222 Remote Similarity NPC40432
0.6222 Remote Similarity NPC161557
0.6207 Remote Similarity NPC216129
0.6207 Remote Similarity NPC130449
0.6207 Remote Similarity NPC248132
0.6102 Remote Similarity NPC328567
0.6 Remote Similarity NPC27843
0.6 Remote Similarity NPC7171
0.5926 Remote Similarity NPC477702
0.5918 Remote Similarity NPC189474
0.5902 Remote Similarity NPC320671
0.5833 Remote Similarity NPC470826
0.5682 Remote Similarity NPC121783
0.5682 Remote Similarity NPC34902
0.5682 Remote Similarity NPC18449
0.5625 Remote Similarity NPC209229
0.5455 Remote Similarity NPC88640
0.5455 Remote Similarity NPC101153
0.5455 Remote Similarity NPC193666
0.5455 Remote Similarity NPC123526
0.5455 Remote Similarity NPC608725
0.5424 Remote Similarity NPC470098
0.5424 Remote Similarity NPC473266
0.541 Remote Similarity NPC470097
0.5333 Remote Similarity NPC244983
0.5312 Remote Similarity NPC114119
0.5312 Remote Similarity NPC286235
0.5312 Remote Similarity NPC471415
0.5283 Remote Similarity NPC287504
0.5283 Remote Similarity NPC611302
0.52 Remote Similarity NPC158331
0.5102 Remote Similarity NPC606146
0.5082 Remote Similarity NPC212890
0.5077 Remote Similarity NPC51328
0.5077 Remote Similarity NPC55158

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC165155 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