Natural Product: NPC212890

Natural Product IDNPC212890
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 [(2S,3R,4R,5S)-5-(4-Hydroxy-3,5-Dimethoxyphenyl)-4-(Hydroxymethyl)-2-(7-Methoxy-1,3-Benzodioxol-5-Yl)Oxolan-3-Yl]Methyl Acetate
IUPAC Name [(2S,3R,4R,5S)-5-(4-hydroxy-3,5-dimethoxyphenyl)-4-(hydroxymethyl)-2-(7-methoxy-1,3-benzodioxol-5-yl)oxolan-3-yl]methyl acetate
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL223923
PubChem CID 44421675
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0001392] Lignans, neolignans and related compounds
      • [CHEMONTID:0003686] Furanoid lignans
        • [CHEMONTID:0001604] Tetrahydrofuran lignans
          • [CHEMONTID:0003423] 7,7'-epoxylignans

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 JUEJBEWUMWMVJE-WVZRZZCNSA-N
Standard InCHI InChI=1S/C24H28O10/c1-12(26)31-10-16-15(9-25)22(13-5-17(28-2)21(27)18(6-13)29-3)34-23(16)14-7-19(30-4)24-20(8-14)32-11-33-24/h5-8,15-16,22-23,25,27H,9-11H2,1-4H3/t15-,16-,22+,23+/m0/s1
SMILES OC[C@H]1[C@H](COC(=O)C)[C@H](O[C@@H]1c1cc(OC)c(c(c1)OC)O)c1cc(OC)c2c(c1)OCO2

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   476.17 Volume:   458.881
?
Van der Waals volume.
Dense:   1.038 LogP:   1.455
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.886
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.272
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   9.0 Rigid Bonds:   22.0
TPSA:   122.14
?
Topological Polar Surface Area.
 H-Bond Acceptor:   10.0
H-Bond Donor:   2.0 Rings:   4.0
Heavy Atoms:   10.0

MedChem Properties

QED Drug-Likeness Score:   0.55 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.973 Fsp3:   0.458
MCE-18:   82.143
?
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:   0.512 Fluc inhibitor:   0.148
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.018
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.37
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.094 Promiscuous compounds:   0.413

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.668 MDCK Permeability:   -5.142
Pgp-inhibitor:   0.823 Pgp-substrate:   0.027
PAMPA:   0.003
?
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%):   0.007 30% Bioavailability (F30%):   0.0
50% Bioavailability (F50%):   0.414

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.468 MRP1:   0.992
Plasma Protein Binding (PPB):   91.108% Volume Distribution (VD):   -0.285
Fu: 8.509%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   0.991 BCRP inhibitor:   0.072
BSEP inhibitor:   0.999

ADMET: Metabolism

CYP1A2-inhibitor:   0.734 CYP1A2-substrate:   0.125
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.163
CYP2C9-inhibitor:   0.008 CYP2C9-substrate:   0.979
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.479
CYP3A4-inhibitor:   0.155 CYP3A4-substrate:   0.99
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.986
HLM stability:   0.248
?
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):  4.735 Half-life (T1/2):  1.979

ADMET: Toxicity

hERG Blockers:  0.051 hERG Blockers (10um):  0.224
Human Hepatotoxicity (H-HT):  0.701 Drug-induced Liver Injury (DILI):  0.886
AMES Toxicity:  0.712 Rat Oral Acute Toxicity:  0.291
Maximum Recommended Daily Dose:  0.357 Skin Sensitization:  0.929
Carcinogencity:  0.83 Eye Corrosion:  0.001
Eye Irritation:  0.492 Respiratory Toxicity:  0.214
Drug-induced Neurotoxicity:  0.451 Ototoxicity:  0.504
Hematotoxicity:  0.734 Drug-induced Nephrotoxicity:  0.591
Genotoxicity:  0.811 RPMI-8226 Immunitoxicity:  0.181
A549 Cytotoxicity:  0.31 Hek293 Cytotoxicity:  0.314
BCF:   0.628
?
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:   3.296
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.861
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.041
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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
NPO25232 Peperomia heyneana Species Piperaceae Eukaryota n.a. n.a. n.a. PMID[17291043]
NPO25232 Peperomia heyneana Species Piperaceae 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
NPT1452 Cell line C8166 Homo sapiens CC50 = 229400.0 nM PMID[8289059]
NPT24 Organism Human immunodeficiency virus 1 Human immunodeficiency virus 1 EC50 = 49800.0 nM DOI[10.1007/s00044-011-9612-6]
NPT2 Others Unspecified n.a. Ratio CC50/EC50 = 4.6 n.a. PMID[9677284]

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 NPC212890 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
0.8727 High Similarity NPC166884
0.8727 High Similarity NPC141569
0.8727 High Similarity NPC477701
0.8571 High Similarity NPC287124
0.8571 High Similarity NPC477702
0.6333 Remote Similarity NPC185071
0.614 Remote Similarity NPC326095
0.5714 Remote Similarity NPC487682
0.5538 Remote Similarity NPC298317
0.5538 Remote Similarity NPC255566
0.5536 Remote Similarity NPC244983
0.5507 Remote Similarity NPC187774
0.5484 Remote Similarity NPC479434
0.5429 Remote Similarity NPC477699
0.5417 Remote Similarity NPC473046
0.5373 Remote Similarity NPC477695
0.5278 Remote Similarity NPC118385
0.5254 Remote Similarity NPC204215
0.5172 Remote Similarity NPC31530
0.5147 Remote Similarity NPC12728
0.5085 Remote Similarity NPC72046
0.5085 Remote Similarity NPC261812
0.5085 Remote Similarity NPC65183
0.5082 Remote Similarity NPC165155
0.5082 Remote Similarity NPC24490

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC212890 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