Natural Product: NPC202582

Natural Product IDNPC202582
Common Name
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The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Rhaphidecursinol B
IUPAC Name (1S,2R)-2-(2,6-dimethoxy-4-prop-2-enylphenoxy)-1-(3,4,5-trimethoxyphenyl)propan-1-ol
Synonyms rhaphidecursinol B
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL462321
PubChem CID 14018327
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0001392] Lignans, neolignans and related compounds

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 KKEKLEUWEJUCRA-SPLOXXLWSA-N
Standard InCHI InChI=1S/C23H30O7/c1-8-9-15-10-17(25-3)23(18(11-15)26-4)30-14(2)21(24)16-12-19(27-5)22(29-7)20(13-16)28-6/h8,10-14,21,24H,1,9H2,2-7H3/t14-,21-/m1/s1
SMILES C=CCc1cc(c(c(c1)OC)O[C@H](C)[C@H](c1cc(c(c(c1)OC)OC)OC)O)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   418.2 Volume:   432.328
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Van der Waals volume.
Dense:   0.967 LogP:   2.545
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.799
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.781
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The logarithm of aqueous solubility value.
Rotatable Bonds:   11.0 Rigid Bonds:   13.0
TPSA:   75.61
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Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   1.0 Rings:   2.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.554 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.231 Fsp3:   0.391
MCE-18:   32.0
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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:   Rejected GSK Rule:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.205 Fluc inhibitor:   0.02
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.025
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.326
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.321 Promiscuous compounds:   0.053

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.663 MDCK Permeability:   -4.797
Pgp-inhibitor:   0.502 Pgp-substrate:   0.003
PAMPA:   0.003
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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%):   0.044 30% Bioavailability (F30%):   0.02
50% Bioavailability (F50%):   0.601

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.832 MRP1:   0.992
Plasma Protein Binding (PPB):   84.573% Volume Distribution (VD):   0.269
Fu: 15.844%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.984
OATP1B3 inhibitor:   0.995 BCRP inhibitor:   0.533
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.513
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.105
CYP2C9-inhibitor:   0.006 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.462 CYP2D6-substrate:   0.926
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   0.989
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.068
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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):  8.405 Half-life (T1/2):  1.706

ADMET: Toxicity

hERG Blockers:  0.217 hERG Blockers (10um):  0.693
Human Hepatotoxicity (H-HT):  0.642 Drug-induced Liver Injury (DILI):  0.591
AMES Toxicity:  0.234 Rat Oral Acute Toxicity:  0.437
Maximum Recommended Daily Dose:  0.576 Skin Sensitization:  0.68
Carcinogencity:  0.488 Eye Corrosion:  0.008
Eye Irritation:  0.418 Respiratory Toxicity:  0.72
Drug-induced Neurotoxicity:  0.854 Ototoxicity:  0.55
Hematotoxicity:  0.298 Drug-induced Nephrotoxicity:  0.318
Genotoxicity:  0.377 RPMI-8226 Immunitoxicity:  0.147
A549 Cytotoxicity:  0.264 Hek293 Cytotoxicity:  0.608
BCF:   1.575
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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:   3.423
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.795
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.891
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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
NPO863 Rhaphidophora decursiva Species Araceae Eukaryota n.a. n.a. n.a. PMID[11421741]
NPO863 Rhaphidophora decursiva Species Araceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO863 Rhaphidophora decursiva Species Araceae 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
NPT91 Cell line KB Homo sapiens ED50 = 10.0 ug ml-1 PubChem BioAssay data set
NPT6 Organism Plasmodium falciparum Plasmodium falciparum IC50 = 4.678 ug.mL-1 PMID[15787455]
NPT6 Organism Plasmodium falciparum Plasmodium falciparum IC50 = 5.372 ug.mL-1 PMID[23398362]
NPT1819 Organism Microsporum canis Arthroderma otae MIC = 50.0 ug.mL-1 PMID[21925888]
NPT327 Organism Microsporum gypseum Microsporum gypseum MIC = 150.0 ug.mL-1 PubChem BioAssay data set
NPT330 Organism Trichophyton mentagrophytes Trichophyton mentagrophytes MIC = 50.0 ug.mL-1 PMID[21353775]
NPT329 Organism Trichophyton rubrum Trichophyton rubrum MIC = 25.0 ug.mL-1 PMID[15043423]
NPT328 Organism Epidermophyton floccosum Epidermophyton floccosum MIC = 50.0 ug.mL-1 PMID[19467876]

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 NPC202582 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 NPC243749
0.8043 Intermediate Similarity NPC25695
0.8 Intermediate Similarity NPC190629
0.8 Intermediate Similarity NPC354196
0.72 Intermediate Similarity NPC484134
0.7 Intermediate Similarity NPC203831
0.6667 Remote Similarity NPC218856
0.6667 Remote Similarity NPC210623
0.6667 Remote Similarity NPC471719
0.6667 Remote Similarity NPC226788
0.6136 Remote Similarity NPC261661
0.6136 Remote Similarity NPC601166
0.6078 Remote Similarity NPC35932
0.6053 Remote Similarity NPC204120
0.5769 Remote Similarity NPC3439
0.5769 Remote Similarity NPC285339
0.5625 Remote Similarity NPC28326
0.5472 Remote Similarity NPC172818
0.54 Remote Similarity NPC604372
0.5385 Remote Similarity NPC273295
0.5385 Remote Similarity NPC470258
0.5385 Remote Similarity NPC222004
0.5385 Remote Similarity NPC602870
0.5273 Remote Similarity NPC485478
0.5192 Remote Similarity NPC307042
0.5094 Remote Similarity NPC473091

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC202582 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