Natural Product: NPC487682

Natural Product IDNPC487682
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 JKDRDNHHEAWWJI-LBSHBVKLSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 132967541
Chemical Classification
  • CHEMONTID:0000000 [Organic 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 JKDRDNHHEAWWJI-LBSHBVKLSA-N
Standard InCHI InChI=1S/C22H24O7/c1-12-16(10-26-13(2)23)22(15-4-6-17(24)19(8-15)25-3)29-21(12)14-5-7-18-20(9-14)28-11-27-18/h4-9,12,16,21-22,24H,10-11H2,1-3H3/t12-,16-,21-,22-/m1/s1
SMILES C[C@@H]1[C@@H](COC(=O)C)[C@@H](c2ccc(c(c2)OC)O)O[C@H]1c1ccc2c(c1)OCO2

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   400.15 Volume:   397.919
?
Van der Waals volume.
Dense:   1.006 LogP:   2.845
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.912
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.014
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   22.0
TPSA:   83.45
?
Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   1.0 Rings:   4.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.765 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.713 Fsp3:   0.409
MCE-18:   76.419
?
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:   0.567 Fluc inhibitor:   0.436
?
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:   0.145
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.192 Promiscuous compounds:   0.214

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.255 MDCK Permeability:   -4.892
Pgp-inhibitor:   0.256 Pgp-substrate:   0.012
PAMPA:   0.089
?
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%):   0.015 30% Bioavailability (F30%):   0.003
50% Bioavailability (F50%):   0.82

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.289 MRP1:   0.908
Plasma Protein Binding (PPB):   96.749% Volume Distribution (VD):   -0.068
Fu: 3.803%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.99
OATP1B3 inhibitor:   0.976 BCRP inhibitor:   0.029
BSEP inhibitor:   0.995

ADMET: Metabolism

CYP1A2-inhibitor:   0.514 CYP1A2-substrate:   0.457
CYP2C19-inhibitor:   0.996 CYP2C19-substrate:   0.528
CYP2C9-inhibitor:   0.004 CYP2C9-substrate:   1.0
CYP2D6-inhibitor:   0.263 CYP2D6-substrate:   0.992
CYP3A4-inhibitor:   0.257 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.812
HLM stability:   0.684
?
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):  4.644 Half-life (T1/2):  1.357

ADMET: Toxicity

hERG Blockers:  0.121 hERG Blockers (10um):  0.497
Human Hepatotoxicity (H-HT):  0.505 Drug-induced Liver Injury (DILI):  0.761
AMES Toxicity:  0.808 Rat Oral Acute Toxicity:  0.326
Maximum Recommended Daily Dose:  0.311 Skin Sensitization:  0.61
Carcinogencity:  0.785 Eye Corrosion:  0.012
Eye Irritation:  0.723 Respiratory Toxicity:  0.235
Drug-induced Neurotoxicity:  0.409 Ototoxicity:  0.399
Hematotoxicity:  0.471 Drug-induced Nephrotoxicity:  0.481
Genotoxicity:  0.866 RPMI-8226 Immunitoxicity:  0.086
A549 Cytotoxicity:  0.15 Hek293 Cytotoxicity:  0.426
BCF:   1.063
?
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:   3.652
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.247
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.638
?
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
NPO40344 Schisandra bicolor var. tuberculata Strain Schisandraceae Eukaryota Fruits n.a. n.a. PMID[28333453]

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
NPT519 Cell line SH-SY5Y Homo sapiens Activity > 15.0 % PMID[28333453]
NPT519 Cell line SH-SY5Y Homo sapiens Activity = 68.6 % PMID[28333453]
NPT519 Cell line SH-SY5Y Homo sapiens Activity = 79.3 % PMID[28333453]
NPT519 Cell line SH-SY5Y Homo sapiens Activity = 88.6 % PMID[28333453]

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 NPC487682 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
0.8036 Intermediate Similarity NPC142547
0.8036 Intermediate Similarity NPC228469
0.7167 Intermediate Similarity NPC88640
0.7167 Intermediate Similarity NPC101153
0.7167 Intermediate Similarity NPC193666
0.7167 Intermediate Similarity NPC123526
0.7167 Intermediate Similarity NPC608725
0.6552 Remote Similarity NPC11258
0.6552 Remote Similarity NPC21867
0.6552 Remote Similarity NPC45774
0.6552 Remote Similarity NPC74914
0.6393 Remote Similarity NPC135777
0.625 Remote Similarity NPC477702
0.6032 Remote Similarity NPC488984
0.6032 Remote Similarity NPC488985
0.597 Remote Similarity NPC471505
0.597 Remote Similarity NPC43514
0.5893 Remote Similarity NPC282703
0.5893 Remote Similarity NPC184733
0.5893 Remote Similarity NPC128208
0.5893 Remote Similarity NPC129570
0.5893 Remote Similarity NPC63238
0.5893 Remote Similarity NPC602603
0.589 Remote Similarity NPC304048
0.5862 Remote Similarity NPC57119
0.5862 Remote Similarity NPC158471
0.5862 Remote Similarity NPC226862
0.5806 Remote Similarity NPC27843
0.5806 Remote Similarity NPC7171
0.5781 Remote Similarity NPC298317
0.5781 Remote Similarity NPC255566
0.5738 Remote Similarity NPC487683
0.5714 Remote Similarity NPC271208
0.5714 Remote Similarity NPC233224
0.5714 Remote Similarity NPC212890
0.5714 Remote Similarity NPC610263
0.5588 Remote Similarity NPC67247
0.5571 Remote Similarity NPC265154
0.5556 Remote Similarity NPC488986
0.5429 Remote Similarity NPC487679
0.5429 Remote Similarity NPC487678
0.5385 Remote Similarity NPC610778
0.5373 Remote Similarity NPC166884
0.5373 Remote Similarity NPC141569
0.5373 Remote Similarity NPC477701
0.5352 Remote Similarity NPC77861
0.5323 Remote Similarity NPC487685
0.5294 Remote Similarity NPC287124
0.5278 Remote Similarity NPC308555
0.5167 Remote Similarity NPC115207
0.5167 Remote Similarity NPC158079
0.5167 Remote Similarity NPC228346
0.5167 Remote Similarity NPC40432
0.5167 Remote Similarity NPC161557
0.5161 Remote Similarity NPC227160
0.5161 Remote Similarity NPC82111
0.5161 Remote Similarity NPC158331
0.5152 Remote Similarity NPC223185
0.5152 Remote Similarity NPC7744
0.5132 Remote Similarity NPC226153
0.5079 Remote Similarity NPC136750
0.5079 Remote Similarity NPC487684
0.5079 Remote Similarity NPC266848
0.5077 Remote Similarity NPC14022
0.5077 Remote Similarity NPC601703

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC487682 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