Natural Product: NPC604095

Natural Product IDNPC604095
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 CVPYYBCSHSCXJQ-DXKBKAGUSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1083413
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 CVPYYBCSHSCXJQ-DXKBKAGUSA-N
Standard InCHI InChI=1S/C21H24O9/c1-28-16-8-11(2-3-12-6-13(23)9-14(24)7-12)4-5-15(16)29-21-20(27)19(26)18(25)17(10-22)30-21/h2-9,17-27H,10H2,1H3/b3-2+/t17-,18-,19+,20-,21-/m1/s1
SMILES COc1cc(/C=C/c2cc(O)cc(O)c2)ccc1O[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   420.14 Volume:   406.76
?
Van der Waals volume.
Dense:   1.033 LogP:   1.672
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.945
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.381
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   19.0
TPSA:   149.07
?
Topological Polar Surface Area.
 H-Bond Acceptor:   9.0
H-Bond Donor:   6.0 Rings:   3.0
Heavy Atoms:   9.0

MedChem Properties

QED Drug-Likeness Score:   0.366 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.728 Fsp3:   0.333
MCE-18:   67.143
?
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:   0 PAINS Alert:   0
Colloidal aggregators:   0.587 Fluc inhibitor:   0.987
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.159
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.702
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.274 Promiscuous compounds:   0.247

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.011 MDCK Permeability:   -5.268
Pgp-inhibitor:   0.0 Pgp-substrate:   0.007
PAMPA:   0.737
?
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):   0.014
20% Bioavailability (F20%):   0.379 30% Bioavailability (F30%):   0.954
50% Bioavailability (F50%):   0.981

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.007 MRP1:   0.009
Plasma Protein Binding (PPB):   76.798% Volume Distribution (VD):   -0.275
Fu: 22.548%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.409
BSEP inhibitor:   0.006

ADMET: Metabolism

CYP1A2-inhibitor:   0.005 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.017 CYP2D6-substrate:   0.021
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.42
?
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):  3.347 Half-life (T1/2):  3.965

ADMET: Toxicity

hERG Blockers:  0.078 hERG Blockers (10um):  0.19
Human Hepatotoxicity (H-HT):  0.794 Drug-induced Liver Injury (DILI):  0.667
AMES Toxicity:  0.923 Rat Oral Acute Toxicity:  0.034
Maximum Recommended Daily Dose:  0.234 Skin Sensitization:  0.994
Carcinogencity:  0.295 Eye Corrosion:  0.0
Eye Irritation:  0.531 Respiratory Toxicity:  0.021
Drug-induced Neurotoxicity:  0.018 Ototoxicity:  0.865
Hematotoxicity:  0.119 Drug-induced Nephrotoxicity:  0.46
Genotoxicity:  0.904 RPMI-8226 Immunitoxicity:  0.105
A549 Cytotoxicity:  0.472 Hek293 Cytotoxicity:  0.717
BCF:   0.603
?
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:   3.185
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.011
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.956
?
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
NPO51412 Gnetum gnemon Species Gnetaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7239 Gnetum parvifolium Species Gnetaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7239 Gnetum parvifolium Species Gnetaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO7239 Gnetum parvifolium Species Gnetaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO7239 Gnetum parvifolium Species Gnetaceae 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
NPT28438 Unchecked Unchecked n.a. Inhibition = 28.0 % PMID[20452207]

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 NPC604095 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
0.7586 Intermediate Similarity NPC26080
0.7586 Intermediate Similarity NPC165686
0.7213 Intermediate Similarity NPC59324
0.7167 Intermediate Similarity NPC479029
0.6984 Remote Similarity NPC294166
0.6984 Remote Similarity NPC115022
0.6984 Remote Similarity NPC65530
0.6885 Remote Similarity NPC248355
0.6774 Remote Similarity NPC55040
0.6667 Remote Similarity NPC302378
0.6418 Remote Similarity NPC98777
0.6364 Remote Similarity NPC37468
0.6333 Remote Similarity NPC166040
0.629 Remote Similarity NPC472024
0.629 Remote Similarity NPC479028
0.629 Remote Similarity NPC270849
0.629 Remote Similarity NPC479031
0.6176 Remote Similarity NPC212770
0.5942 Remote Similarity NPC475084
0.5938 Remote Similarity NPC26653
0.5938 Remote Similarity NPC80600
0.5909 Remote Similarity NPC85799
0.5909 Remote Similarity NPC303422
0.5909 Remote Similarity NPC218003
0.5882 Remote Similarity NPC8497
0.5818 Remote Similarity NPC474565
0.5735 Remote Similarity NPC242028
0.5735 Remote Similarity NPC276753
0.5735 Remote Similarity NPC203230
0.5735 Remote Similarity NPC252169
0.5735 Remote Similarity NPC205796
0.5714 Remote Similarity NPC9912
0.5692 Remote Similarity NPC214910
0.5676 Remote Similarity NPC279298
0.5652 Remote Similarity NPC479030
0.5652 Remote Similarity NPC246947
0.5571 Remote Similarity NPC260681
0.5541 Remote Similarity NPC286235
0.5536 Remote Similarity NPC228907
0.5467 Remote Similarity NPC38041
0.5467 Remote Similarity NPC22150
0.5455 Remote Similarity NPC481303
0.5455 Remote Similarity NPC210478
0.5429 Remote Similarity NPC185778
0.541 Remote Similarity NPC25817
0.541 Remote Similarity NPC152722
0.5397 Remote Similarity NPC145900
0.5385 Remote Similarity NPC49074
0.5385 Remote Similarity NPC93924
0.5362 Remote Similarity NPC100389
0.5309 Remote Similarity NPC152346
0.5309 Remote Similarity NPC197703
0.5303 Remote Similarity NPC162093
0.5294 Remote Similarity NPC59692
0.5286 Remote Similarity NPC469661
0.5263 Remote Similarity NPC227902
0.5263 Remote Similarity NPC18979
0.525 Remote Similarity NPC245615
0.5238 Remote Similarity NPC200092
0.5238 Remote Similarity NPC12308
0.5233 Remote Similarity NPC469654
0.52 Remote Similarity NPC158635
0.52 Remote Similarity NPC229882
0.5172 Remote Similarity NPC223335
0.5172 Remote Similarity NPC40920
0.5167 Remote Similarity NPC142319
0.5135 Remote Similarity NPC148273
0.5125 Remote Similarity NPC43508
0.5119 Remote Similarity NPC23431
0.5114 Remote Similarity NPC44507
0.5082 Remote Similarity NPC484157
0.5079 Remote Similarity NPC299144
0.5075 Remote Similarity NPC23084
0.5075 Remote Similarity NPC604356
0.5068 Remote Similarity NPC210192
0.5068 Remote Similarity NPC189115
0.5062 Remote Similarity NPC299706
0.5062 Remote Similarity NPC115466
0.5062 Remote Similarity NPC39657
0.5062 Remote Similarity NPC61604

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC604095 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