Natural Product: NPC487683

Natural Product IDNPC487683
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 QCHJXHQTUAMJBH-BINDOVRGSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID n.a.
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 QCHJXHQTUAMJBH-BINDOVRGSA-N
Standard InCHI InChI=1S/C20H24O5/c1-11-12(2)20(14-5-7-15(21)18(10-14)24-4)25-19(11)13-6-8-17(23-3)16(22)9-13/h5-12,19-22H,1-4H3/t11-,12+,19-,20-/m1/s1
SMILES C[C@@H]1[C@H](C)[C@H](c2ccc(c(c2)OC)O)O[C@H]1c1ccc(c(c1)O)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   344.16 Volume:   356.939
?
Van der Waals volume.
Dense:   0.964 LogP:   2.589
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.67
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.391
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   17.0
TPSA:   68.15
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   2.0 Rings:   3.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.87 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.428 Fsp3:   0.4
MCE-18:   62.429
?
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:   0.308 Fluc inhibitor:   0.392
?
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:   0.016
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.38 Promiscuous compounds:   0.247

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.236 MDCK Permeability:   -4.866
Pgp-inhibitor:   0.03 Pgp-substrate:   0.13
PAMPA:   0.142
?
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%):   0.124 30% Bioavailability (F30%):   0.119
50% Bioavailability (F50%):   0.972

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.008 MRP1:   0.753
Plasma Protein Binding (PPB):   89.182% Volume Distribution (VD):   -0.202
Fu: 11.381%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.995
OATP1B3 inhibitor:   0.995 BCRP inhibitor:   0.426
BSEP inhibitor:   0.076

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.128
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.997
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.541
CYP2D6-inhibitor:   0.001 CYP2D6-substrate:   0.028
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.995
HLM stability:   0.354
?
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):  5.649 Half-life (T1/2):  1.901

ADMET: Toxicity

hERG Blockers:  0.113 hERG Blockers (10um):  0.589
Human Hepatotoxicity (H-HT):  0.479 Drug-induced Liver Injury (DILI):  0.545
AMES Toxicity:  0.603 Rat Oral Acute Toxicity:  0.3
Maximum Recommended Daily Dose:  0.242 Skin Sensitization:  0.656
Carcinogencity:  0.622 Eye Corrosion:  0.137
Eye Irritation:  0.923 Respiratory Toxicity:  0.702
Drug-induced Neurotoxicity:  0.303 Ototoxicity:  0.445
Hematotoxicity:  0.301 Drug-induced Nephrotoxicity:  0.329
Genotoxicity:  0.241 RPMI-8226 Immunitoxicity:  0.139
A549 Cytotoxicity:  0.388 Hek293 Cytotoxicity:  0.492
BCF:   1.452
?
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:   3.812
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.246
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.586
?
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 = 71.0 % PMID[28333453]
NPT519 Cell line SH-SY5Y Homo sapiens Activity = 77.1 % PMID[28333453]
NPT519 Cell line SH-SY5Y Homo sapiens Activity = 64.5 % 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 NPC487683 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
0.8293 Intermediate Similarity NPC282703
0.8293 Intermediate Similarity NPC184733
0.8293 Intermediate Similarity NPC128208
0.8293 Intermediate Similarity NPC129570
0.8293 Intermediate Similarity NPC63238
0.8293 Intermediate Similarity NPC602603
0.7826 Intermediate Similarity NPC11258
0.7826 Intermediate Similarity NPC21867
0.7826 Intermediate Similarity NPC45774
0.7826 Intermediate Similarity NPC74914
0.7609 Intermediate Similarity NPC487684
0.75 Intermediate Similarity NPC488986
0.7059 Intermediate Similarity NPC142547
0.7059 Intermediate Similarity NPC228469
0.6863 Remote Similarity NPC135777
0.6383 Remote Similarity NPC242807
0.6383 Remote Similarity NPC142985
0.6383 Remote Similarity NPC153739
0.6102 Remote Similarity NPC77861
0.6 Remote Similarity NPC147379
0.6 Remote Similarity NPC158331
0.6 Remote Similarity NPC469480
0.5738 Remote Similarity NPC487682
0.5714 Remote Similarity NPC115207
0.5714 Remote Similarity NPC158079
0.5714 Remote Similarity NPC228346
0.5714 Remote Similarity NPC40432
0.5714 Remote Similarity NPC161557
0.5556 Remote Similarity NPC27843
0.5556 Remote Similarity NPC7171
0.5536 Remote Similarity NPC488984
0.5536 Remote Similarity NPC488985
0.5484 Remote Similarity NPC470372
0.5435 Remote Similarity NPC216929
0.5435 Remote Similarity NPC312713
0.5435 Remote Similarity NPC126935
0.5435 Remote Similarity NPC65933
0.5435 Remote Similarity NPC57268
0.5435 Remote Similarity NPC172676
0.5283 Remote Similarity NPC126409
0.5283 Remote Similarity NPC99572
0.52 Remote Similarity NPC204215
0.5192 Remote Similarity NPC175067
0.5172 Remote Similarity NPC471942
0.5106 Remote Similarity NPC159418
0.5088 Remote Similarity NPC223185
0.5088 Remote Similarity NPC610778
0.5085 Remote Similarity NPC88640
0.5085 Remote Similarity NPC101153
0.5085 Remote Similarity NPC193666
0.5085 Remote Similarity NPC123526
0.5085 Remote Similarity NPC608725

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC487683 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