Natural Product: NPC261661

Natural Product IDNPC261661
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (S)-Virolongin B
IUPAC Name 1,3-dimethoxy-5-prop-2-enyl-2-[(2S)-1-(3,4,5-trimethoxyphenyl)propan-2-yl]oxybenzene
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL3577103
PubChem CID 91734155
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0002448] Benzenoids
      • [CHEMONTID:0002279] Benzene and substituted derivatives
        • [CHEMONTID:0004113] Methoxybenzenes
          • [CHEMONTID:0004111] Dimethoxybenzenes

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 ZOPUPXKPXCSWAE-HNNXBMFYSA-N
Standard InCHI InChI=1S/C23H30O6/c1-8-9-16-11-20(26-5)23(21(12-16)27-6)29-15(2)10-17-13-18(24-3)22(28-7)19(14-17)25-4/h8,11-15H,1,9-10H2,2-7H3/t15-/m0/s1
SMILES C=CCc1cc(OC)c(c(c1)OC)O[C@H](Cc1cc(OC)c(c(c1)OC)OC)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   402.2 Volume:   423.537
?
Van der Waals volume.
Dense:   0.95 LogP:   3.087
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.158
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.941
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   11.0 Rigid Bonds:   13.0
TPSA:   55.38
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   0.0 Rings:   2.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.517 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.84 Fsp3:   0.391
MCE-18:   30.0
?
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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.195 Fluc inhibitor:   0.009
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.023
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.444
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.645 Promiscuous compounds:   0.03

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.731 MDCK Permeability:   -4.787
Pgp-inhibitor:   0.886 Pgp-substrate:   0.004
PAMPA:   0.0
?
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%):   0.098 30% Bioavailability (F30%):   0.055
50% Bioavailability (F50%):   0.296

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.528 MRP1:   0.994
Plasma Protein Binding (PPB):   91.723% Volume Distribution (VD):   0.193
Fu: 9.481%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   0.993 BCRP inhibitor:   0.182
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.001 CYP1A2-substrate:   0.995
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.977
CYP2C9-inhibitor:   0.944 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.03 CYP2D6-substrate:   1.0
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.534 CYP2C8-inhibitor:   1.0
HLM stability:   0.149
?
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):  7.855 Half-life (T1/2):  1.321

ADMET: Toxicity

hERG Blockers:  0.293 hERG Blockers (10um):  0.736
Human Hepatotoxicity (H-HT):  0.579 Drug-induced Liver Injury (DILI):  0.633
AMES Toxicity:  0.334 Rat Oral Acute Toxicity:  0.551
Maximum Recommended Daily Dose:  0.568 Skin Sensitization:  0.817
Carcinogencity:  0.562 Eye Corrosion:  0.249
Eye Irritation:  0.792 Respiratory Toxicity:  0.797
Drug-induced Neurotoxicity:  0.926 Ototoxicity:  0.411
Hematotoxicity:  0.252 Drug-induced Nephrotoxicity:  0.489
Genotoxicity:  0.153 RPMI-8226 Immunitoxicity:  0.157
A549 Cytotoxicity:  0.258 Hek293 Cytotoxicity:  0.442
BCF:   2.511
?
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:   4.105
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.445
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.721
?
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
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota seeds n.a. n.a. PMID[17998162]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota n.a. n.a. n.a. PMID[1955885]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota n.a. fruit n.a. PMID[20879744]
NPO33212 ocotea cymosa Species Lauraceae Eukaryota stems or bark Zahamena National Park, 1728'45?S, 04844'10?E, Madagascar 2000-JAN PMID[25650896]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota n.a. n.a. n.a. PMID[27419473]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota n.a. n.a. n.a. PMID[32515616]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota n.a. n.a. n.a. PMID[33444950]
NPO33212 ocotea cymosa Species Lauraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2665 Andinobates fulguritus Species Dendrobatidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8303 Catalpa bignonioides Species Bignoniaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17811 Cephalonoplos segetum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5162 Comaster multifida Species Comatulidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8532 Helipterum tenellum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1382 Hyptis tomentosa Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4539 Ipomoea cristulata Species Convolvulaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19928 Lachnoanaerobaculum saburreum Species Lachnospiraceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO28409 Lens phaseoloides Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO490 Lophozonia menziesii Species Nothofagaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5746 Pancratium trianthum Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO6113 Piper pedicellosum Species Piperaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7393 Esenbeckia nesiotica Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5334 Rhodotypos scandens Species Rosaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7237 Xanthostemon oppositifolius Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota n.a. n.a. Database[FooDB]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota Aril n.a. n.a. Database[FooDB]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota Bark n.a. n.a. Database[FooDB]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota Leaf n.a. n.a. Database[FooDB]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota Leaf Essent. Oil n.a. n.a. Database[FooDB]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota Seed n.a. n.a. Database[FooDB]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota n.a. n.a. Database[FooDB]
NPO1382 Hyptis tomentosa Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO8303 Catalpa bignonioides Species Bignoniaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota n.a. n.a. Database[Phenol-Explorer]
NPO1382 Hyptis tomentosa Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO8303 Catalpa bignonioides Species Bignoniaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO1382 Hyptis tomentosa Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota n.a. n.a. n.a. Database[Title]
NPO5241 Myristica fragrans Species Myristicaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO7237 Xanthostemon oppositifolius Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28409 Lens phaseoloides Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8532 Helipterum tenellum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1382 Hyptis tomentosa Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6113 Piper pedicellosum Species Piperaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5162 Comaster multifida Species Comatulidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19928 Lachnoanaerobaculum saburreum Species Lachnospiraceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO4539 Ipomoea cristulata Species Convolvulaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO490 Lophozonia menziesii Species Nothofagaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17811 Cephalonoplos segetum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5746 Pancratium trianthum Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7393 Esenbeckia nesiotica Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5334 Rhodotypos scandens Species Rosaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2665 Andinobates fulguritus Species Dendrobatidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8303 Catalpa bignonioides Species Bignoniaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5241 Myristica fragrans Species Myristicaceae 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
NPT6 Organism Plasmodium falciparum Plasmodium falciparum IC50 = 3300.0 nM PMID[25650896]
NPT6 Organism Plasmodium falciparum Plasmodium falciparum IC50 = 3100.0 nM PMID[25650896]

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 NPC261661 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 NPC601166
0.7805 Intermediate Similarity NPC611354
0.7 Intermediate Similarity NPC601172
0.697 Remote Similarity NPC204120
0.6279 Remote Similarity NPC28326
0.6136 Remote Similarity NPC202582
0.6136 Remote Similarity NPC243749
0.6 Remote Similarity NPC604372
0.5745 Remote Similarity NPC307042
0.5366 Remote Similarity NPC119949
0.52 Remote Similarity NPC190629
0.52 Remote Similarity NPC354196
0.5094 Remote Similarity NPC471719

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC261661 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