Natural Product: NPC486558

Natural Product IDNPC486558
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 CRMXIJILTLLGMR-PZPWOCDFSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 44559567
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0001392] Lignans, neolignans and related compounds
      • [CHEMONTID:0003686] Furanoid lignans
        • [CHEMONTID:0001604] Tetrahydrofuran lignans
          • [CHEMONTID:0003422] 7,9'-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 CRMXIJILTLLGMR-PZPWOCDFSA-N
Standard InCHI InChI=1S/C21H26O7/c1-25-17-7-12(4-5-16(17)23)6-14-11-28-21(15(14)10-22)13-8-18(26-2)20(24)19(9-13)27-3/h4-5,7-9,14-15,21-24H,6,10-11H2,1-3H3/t14-,15-,21+/m1/s1
SMILES COc1cc(ccc1O)C[C@@H]1CO[C@@H](c2cc(c(c(c2)OC)O)OC)[C@@H]1CO

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   390.17 Volume:   391.816
?
Van der Waals volume.
Dense:   0.996 LogP:   1.199
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.573
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.644
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   7.0 Rigid Bonds:   17.0
TPSA:   97.61
?
Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   3.0 Rings:   3.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.669 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.503 Fsp3:   0.429
MCE-18:   62.067
?
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:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   1 PAINS Alert:   0
Colloidal aggregators:   0.185 Fluc inhibitor:   0.264
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.022
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.283
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.144 Promiscuous compounds:   0.242

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.415 MDCK Permeability:   -5.069
Pgp-inhibitor:   0.868 Pgp-substrate:   0.358
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):   0.01
20% Bioavailability (F20%):   0.391 30% Bioavailability (F30%):   0.359
50% Bioavailability (F50%):   0.968

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.019 MRP1:   0.921
Plasma Protein Binding (PPB):   89.502% Volume Distribution (VD):   -0.209
Fu: 12.496%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.998
OATP1B3 inhibitor:   0.982 BCRP inhibitor:   0.786
BSEP inhibitor:   0.981

ADMET: Metabolism

CYP1A2-inhibitor:   0.059 CYP1A2-substrate:   0.619
CYP2C19-inhibitor:   0.999 CYP2C19-substrate:   0.163
CYP2C9-inhibitor:   0.807 CYP2C9-substrate:   0.282
CYP2D6-inhibitor:   0.122 CYP2D6-substrate:   0.712
CYP3A4-inhibitor:   0.588 CYP3A4-substrate:   0.95
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.144
?
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):  8.104 Half-life (T1/2):  1.929

ADMET: Toxicity

hERG Blockers:  0.064 hERG Blockers (10um):  0.351
Human Hepatotoxicity (H-HT):  0.731 Drug-induced Liver Injury (DILI):  0.614
AMES Toxicity:  0.68 Rat Oral Acute Toxicity:  0.3
Maximum Recommended Daily Dose:  0.332 Skin Sensitization:  0.935
Carcinogencity:  0.423 Eye Corrosion:  0.007
Eye Irritation:  0.94 Respiratory Toxicity:  0.54
Drug-induced Neurotoxicity:  0.471 Ototoxicity:  0.528
Hematotoxicity:  0.489 Drug-induced Nephrotoxicity:  0.386
Genotoxicity:  0.586 RPMI-8226 Immunitoxicity:  0.169
A549 Cytotoxicity:  0.649 Hek293 Cytotoxicity:  0.554
BCF:   0.959
?
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:   3.469
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.693
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.984
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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
NPO40954 Wikstroemia elliptica Species Thymelaeaceae Eukaryota n.a. n.a. n.a. PMID[3783168]

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
NPT168 Cell line P388 Mus musculus ED50 = 0.33 ug ml-1 PMID[3783168]

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 NPC486558 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
0.8868 High Similarity NPC282833
0.8846 High Similarity NPC187998
0.8846 High Similarity NPC257582
0.8846 High Similarity NPC241522
0.7895 Intermediate Similarity NPC42300
0.7759 Intermediate Similarity NPC64201
0.629 Remote Similarity NPC67247
0.6226 Remote Similarity NPC31344
0.6226 Remote Similarity NPC317769
0.6071 Remote Similarity NPC126409
0.6071 Remote Similarity NPC99572
0.6061 Remote Similarity NPC267091
0.6034 Remote Similarity NPC478955
0.6034 Remote Similarity NPC478700
0.6 Remote Similarity NPC185307
0.5946 Remote Similarity NPC39657
0.5921 Remote Similarity NPC476356
0.5857 Remote Similarity NPC252402
0.5857 Remote Similarity NPC102934
0.5833 Remote Similarity NPC206882
0.5821 Remote Similarity NPC281780
0.5789 Remote Similarity NPC470950
0.5753 Remote Similarity NPC605526
0.5714 Remote Similarity NPC23646
0.5714 Remote Similarity NPC485397
0.5714 Remote Similarity NPC610652
0.566 Remote Similarity NPC85488
0.5645 Remote Similarity NPC273657
0.5556 Remote Similarity NPC272
0.5556 Remote Similarity NPC77040
0.5556 Remote Similarity NPC485398
0.55 Remote Similarity NPC173308
0.55 Remote Similarity NPC181079
0.5469 Remote Similarity NPC277804
0.5417 Remote Similarity NPC67467
0.541 Remote Similarity NPC287504
0.541 Remote Similarity NPC611302
0.5405 Remote Similarity NPC472711
0.5397 Remote Similarity NPC46591
0.5397 Remote Similarity NPC471942
0.5357 Remote Similarity NPC115207
0.5357 Remote Similarity NPC158079
0.5357 Remote Similarity NPC228346
0.5357 Remote Similarity NPC242807
0.5357 Remote Similarity NPC40432
0.5357 Remote Similarity NPC161557
0.5357 Remote Similarity NPC153739
0.5303 Remote Similarity NPC610284
0.5294 Remote Similarity NPC608199
0.5263 Remote Similarity NPC487676
0.5246 Remote Similarity NPC68779
0.5246 Remote Similarity NPC108598
0.5246 Remote Similarity NPC487680
0.5238 Remote Similarity NPC475875
0.5185 Remote Similarity NPC141765
0.5185 Remote Similarity NPC244983
0.5185 Remote Similarity NPC34103
0.5152 Remote Similarity NPC145144
0.5152 Remote Similarity NPC606339
0.5147 Remote Similarity NPC278961
0.5147 Remote Similarity NPC113680
0.5139 Remote Similarity NPC606627
0.5079 Remote Similarity NPC275950
0.5077 Remote Similarity NPC47181

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC486558 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