Natural Product: NPC483654

Natural Product IDNPC483654
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 IWLDUPODTWQNBQ-INDMIFKZSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 10992991
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0001392] Lignans, neolignans and related compounds
      • [CHEMONTID:0001510] Lignan lactones

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 IWLDUPODTWQNBQ-INDMIFKZSA-N
Standard InCHI InChI=1S/C21H18O8/c1-24-12-5-3-10(7-14(12)25-2)18-16-17(21(23)28-18)19(29-20(16)22)11-4-6-13-15(8-11)27-9-26-13/h3-8,16-19H,9H2,1-2H3/t16-,17-,18+,19+/m0/s1
SMILES COc1ccc(cc1OC)[C@@H]1[C@@H]2[C@@H]([C@@H](c3ccc4c(c3)OCO4)OC2=O)C(=O)O1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   398.1 Volume:   378.22
?
Van der Waals volume.
Dense:   1.053 LogP:   2.331
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.598
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.175
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   27.0
TPSA:   89.52
?
Topological Polar Surface Area.
 H-Bond Acceptor:   8.0
H-Bond Donor:   0.0 Rings:   5.0
Heavy Atoms:   8.0

MedChem Properties

QED Drug-Likeness Score:   0.726 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.589 Fsp3:   0.333
MCE-18:   90.643
?
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:   0 PAINS Alert:   0
Colloidal aggregators:   0.412 Fluc inhibitor:   0.712
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.027
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.442
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.278 Promiscuous compounds:   0.278

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.108 MDCK Permeability:   -4.784
Pgp-inhibitor:   0.927 Pgp-substrate:   0.003
PAMPA:   0.147
?
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):   0.001
20% Bioavailability (F20%):   0.002 30% Bioavailability (F30%):   0.001
50% Bioavailability (F50%):   0.255

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.008 MRP1:   0.833
Plasma Protein Binding (PPB):   97.912% Volume Distribution (VD):   -0.281
Fu: 2.284%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.926
OATP1B3 inhibitor:   0.995 BCRP inhibitor:   0.138
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.988 CYP1A2-substrate:   0.854
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.003
CYP2C9-inhibitor:   0.466 CYP2C9-substrate:   0.254
CYP2D6-inhibitor:   0.743 CYP2D6-substrate:   0.999
CYP3A4-inhibitor:   0.999 CYP3A4-substrate:   0.999
CYP2B6-substrate:   0.001 CYP2C8-inhibitor:   0.001
HLM stability:   0.796
?
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):  3.531 Half-life (T1/2):  3.019

ADMET: Toxicity

hERG Blockers:  0.068 hERG Blockers (10um):  0.39
Human Hepatotoxicity (H-HT):  0.509 Drug-induced Liver Injury (DILI):  0.984
AMES Toxicity:  0.614 Rat Oral Acute Toxicity:  0.162
Maximum Recommended Daily Dose:  0.247 Skin Sensitization:  0.933
Carcinogencity:  0.772 Eye Corrosion:  0.268
Eye Irritation:  0.911 Respiratory Toxicity:  0.127
Drug-induced Neurotoxicity:  0.523 Ototoxicity:  0.277
Hematotoxicity:  0.484 Drug-induced Nephrotoxicity:  0.885
Genotoxicity:  0.947 RPMI-8226 Immunitoxicity:  0.104
A549 Cytotoxicity:  0.147 Hek293 Cytotoxicity:  0.13
BCF:   1.286
?
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:   4.054
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.661
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.024
?
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
NPO11997 Leucophyllum ambiguum Species Scrophulariaceae Eukaryota n.a. n.a. n.a. PMID[12608853]
NPO11997 Leucophyllum ambiguum Species Scrophulariaceae Eukaryota n.a. n.a. n.a. PMID[32239935]
NPO11997 Leucophyllum ambiguum Species Scrophulariaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11997 Leucophyllum ambiguum Species Scrophulariaceae 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
NPT204 Individual protein Acetylcholinesterase Homo sapiens IC50 = 158.0 nM PMID[32239935]
NPT204 Individual protein Acetylcholinesterase Homo sapiens Inhibition > 90.0 % PMID[32239935]

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 NPC483654 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
0.7551 Intermediate Similarity NPC483653
0.6889 Remote Similarity NPC57119
0.6889 Remote Similarity NPC158471
0.6889 Remote Similarity NPC226862
0.6667 Remote Similarity NPC480478
0.6596 Remote Similarity NPC227160
0.6596 Remote Similarity NPC82111
0.625 Remote Similarity NPC483651
0.6 Remote Similarity NPC271208
0.6 Remote Similarity NPC233224
0.6 Remote Similarity NPC610263
0.5882 Remote Similarity NPC483652
0.58 Remote Similarity NPC136750
0.58 Remote Similarity NPC266848
0.5745 Remote Similarity NPC171928
0.5745 Remote Similarity NPC158526
0.5745 Remote Similarity NPC129687
0.5745 Remote Similarity NPC33611
0.5745 Remote Similarity NPC16830
0.5745 Remote Similarity NPC100223
0.5741 Remote Similarity NPC24257
0.5741 Remote Similarity NPC153620
0.5686 Remote Similarity NPC189474
0.5667 Remote Similarity NPC308555
0.5517 Remote Similarity NPC254163
0.5472 Remote Similarity NPC14022
0.5472 Remote Similarity NPC601703
0.5333 Remote Similarity NPC216929
0.5333 Remote Similarity NPC312713
0.5333 Remote Similarity NPC126935
0.5333 Remote Similarity NPC65933
0.5333 Remote Similarity NPC57268
0.5333 Remote Similarity NPC172676
0.5286 Remote Similarity NPC186316
0.5273 Remote Similarity NPC135777
0.5273 Remote Similarity NPC7744
0.5192 Remote Similarity NPC487685
0.5179 Remote Similarity NPC142547
0.5179 Remote Similarity NPC228469
0.5179 Remote Similarity NPC298317
0.5179 Remote Similarity NPC255566
0.5179 Remote Similarity NPC488984
0.5179 Remote Similarity NPC488985
0.5167 Remote Similarity NPC302506
0.5167 Remote Similarity NPC241846
0.5167 Remote Similarity NPC93610
0.5167 Remote Similarity NPC600032
0.5106 Remote Similarity NPC121783
0.5106 Remote Similarity NPC34902
0.5106 Remote Similarity NPC18449
0.5088 Remote Similarity NPC474139

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC483654 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