Natural Product: NPC263124

Natural Product IDNPC263124
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 KOWMJRJXZMEZLD-SRLQQUAWSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 101663451
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 KOWMJRJXZMEZLD-SRLQQUAWSA-N
Standard InCHI InChI=1S/C22H26O8/c1-25-15-5-11(6-16(26-2)19(15)23)21-13-9-30-22(14(13)10-29-21)12-7-17(27-3)20(24)18(8-12)28-4/h5-8,13-14,21-24H,9-10H2,1-4H3/t13-,14-,21-,22+/m1/s1
SMILES COc1cc(cc(c1O)OC)[C@@H]1[C@@H]2CO[C@@H](c3cc(c(c(c3)OC)O)OC)[C@@H]2CO1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   418.16 Volume:   409.345
?
Van der Waals volume.
Dense:   1.022 LogP:   0.909
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.239
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.829
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   21.0
TPSA:   95.84
?
Topological Polar Surface Area.
 H-Bond Acceptor:   8.0
H-Bond Donor:   2.0 Rings:   4.0
Heavy Atoms:   8.0

MedChem Properties

QED Drug-Likeness Score:   0.738 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.758 Fsp3:   0.455
MCE-18:   81.0
?
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:   0.222 Fluc inhibitor:   0.328
?
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:   0.278
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.287 Promiscuous compounds:   0.524

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.473 MDCK Permeability:   -4.96
Pgp-inhibitor:   0.858 Pgp-substrate:   0.179
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):   0.002
20% Bioavailability (F20%):   0.024 30% Bioavailability (F30%):   0.01
50% Bioavailability (F50%):   0.839

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.027 MRP1:   0.974
Plasma Protein Binding (PPB):   84.394% Volume Distribution (VD):   -0.269
Fu: 14.273%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   0.996 BCRP inhibitor:   0.517
BSEP inhibitor:   0.92

ADMET: Metabolism

CYP1A2-inhibitor:   0.99 CYP1A2-substrate:   0.77
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.125
CYP2C9-inhibitor:   0.554 CYP2C9-substrate:   0.536
CYP2D6-inhibitor:   0.38 CYP2D6-substrate:   0.074
CYP3A4-inhibitor:   0.768 CYP3A4-substrate:   0.037
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.983
HLM stability:   0.364
?
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):  6.879 Half-life (T1/2):  2.563

ADMET: Toxicity

hERG Blockers:  0.068 hERG Blockers (10um):  0.449
Human Hepatotoxicity (H-HT):  0.685 Drug-induced Liver Injury (DILI):  0.82
AMES Toxicity:  0.532 Rat Oral Acute Toxicity:  0.285
Maximum Recommended Daily Dose:  0.388 Skin Sensitization:  0.755
Carcinogencity:  0.464 Eye Corrosion:  0.022
Eye Irritation:  0.967 Respiratory Toxicity:  0.513
Drug-induced Neurotoxicity:  0.331 Ototoxicity:  0.26
Hematotoxicity:  0.474 Drug-induced Nephrotoxicity:  0.444
Genotoxicity:  0.518 RPMI-8226 Immunitoxicity:  0.193
A549 Cytotoxicity:  0.177 Hek293 Cytotoxicity:  0.301
BCF:   1.093
?
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:   3.709
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.016
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.411
?
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
NPO2073 Ancistrocladus korupensis Species Ancistrocladaceae Eukaryota n.a. Cameroon n.a. PMID[11430019]
NPO2073 Ancistrocladus korupensis Species Ancistrocladaceae Eukaryota n.a. n.a. n.a. PMID[19299148]
NPO29118 Euonymus alatus Species Celastraceae Eukaryota leaves and twigs n.a. n.a. PMID[21435874]
NPO2073 Ancistrocladus korupensis Species Ancistrocladaceae Eukaryota n.a. n.a. n.a. PMID[9249970]
NPO2073 Ancistrocladus korupensis Species Ancistrocladaceae Eukaryota n.a. n.a. n.a. PMID[9873424]
NPO2073 Ancistrocladus korupensis Species Ancistrocladaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29118 Euonymus alatus Species Celastraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29118 Euonymus alatus Species Celastraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO2073 Ancistrocladus korupensis Species Ancistrocladaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO29118 Euonymus alatus Species Celastraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO29118 Euonymus alatus Species Celastraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO29118 Euonymus alatus Species Celastraceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO29118 Euonymus alatus Species Celastraceae 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

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 NPC263124 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 NPC141765
1.0 High Similarity NPC34103
0.8649 High Similarity NPC165155
0.8649 High Similarity NPC24490
0.8 Intermediate Similarity NPC126409
0.8 Intermediate Similarity NPC99572
0.7805 Intermediate Similarity NPC479434
0.7442 Intermediate Similarity NPC185071
0.7 Intermediate Similarity NPC115207
0.7 Intermediate Similarity NPC158079
0.7 Intermediate Similarity NPC228346
0.7 Intermediate Similarity NPC40432
0.7 Intermediate Similarity NPC161557
0.6977 Remote Similarity NPC27159
0.6977 Remote Similarity NPC186220
0.6957 Remote Similarity NPC298317
0.6957 Remote Similarity NPC255566
0.6486 Remote Similarity NPC281864
0.6486 Remote Similarity NPC328682
0.6486 Remote Similarity NPC54321
0.6 Remote Similarity NPC244983
0.5957 Remote Similarity NPC27843
0.5957 Remote Similarity NPC7171
0.5833 Remote Similarity NPC287504
0.5833 Remote Similarity NPC611302
0.5714 Remote Similarity NPC473092
0.5714 Remote Similarity NPC473093
0.5714 Remote Similarity NPC8050
0.5686 Remote Similarity NPC12728
0.5614 Remote Similarity NPC216129
0.5614 Remote Similarity NPC130449
0.5614 Remote Similarity NPC248132
0.561 Remote Similarity NPC121783
0.561 Remote Similarity NPC34902
0.561 Remote Similarity NPC18449
0.5581 Remote Similarity NPC204215
0.5517 Remote Similarity NPC328567
0.5455 Remote Similarity NPC148893
0.5455 Remote Similarity NPC222127
0.5455 Remote Similarity NPC25333
0.5455 Remote Similarity NPC49235
0.5455 Remote Similarity NPC82862
0.5385 Remote Similarity NPC88640
0.5385 Remote Similarity NPC101153
0.5385 Remote Similarity NPC193666
0.5385 Remote Similarity NPC123526
0.5385 Remote Similarity NPC608725
0.5333 Remote Similarity NPC320671
0.5333 Remote Similarity NPC326095
0.5306 Remote Similarity NPC478955
0.5306 Remote Similarity NPC478700
0.5283 Remote Similarity NPC477702
0.5254 Remote Similarity NPC470826
0.5246 Remote Similarity NPC114119
0.5246 Remote Similarity NPC286235
0.5246 Remote Similarity NPC471415
0.5185 Remote Similarity NPC486558
0.5122 Remote Similarity NPC146355
0.5122 Remote Similarity NPC131747
0.5122 Remote Similarity NPC257682
0.5106 Remote Similarity NPC158331
0.5098 Remote Similarity NPC223185
0.5098 Remote Similarity NPC610778
0.5085 Remote Similarity NPC475738

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC263124 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