Natural Product: NPC199658

Natural Product IDNPC199658
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 CLVZIESVQOWZKS-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 511784
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000145] Coumarins and derivatives
        • [CHEMONTID:0003484] Pyranocoumarins
          • [CHEMONTID:0003485] Angular pyranocoumarins

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 CLVZIESVQOWZKS-UHFFFAOYSA-N
Standard InCHI InChI=1S/C19H20O6/c1-10(2)9-14(21)24-18-16(22)15-12(25-19(18,3)4)7-5-11-6-8-13(20)23-17(11)15/h5-9,16,18,22H,1-4H3
SMILES CC(=CC(=O)OC1C(c2c(ccc3ccc(=O)oc23)OC1(C)C)O)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   344.13 Volume:   345.797
?
Van der Waals volume.
Dense:   0.995 LogP:   2.599
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.301
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.209
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   19.0
TPSA:   85.97
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   1.0 Rings:   3.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.512 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.7 Fsp3:   0.368
MCE-18:   67.846
?
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:   0.22 Fluc inhibitor:   0.021
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.991
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.508
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.106 Promiscuous compounds:   0.009

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.125 MDCK Permeability:   -4.71
Pgp-inhibitor:   0.001 Pgp-substrate:   0.0
PAMPA:   0.43
?
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):   0.003
20% Bioavailability (F20%):   0.777 30% Bioavailability (F30%):   0.859
50% Bioavailability (F50%):   0.993

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.008 MRP1:   0.999
Plasma Protein Binding (PPB):   94.914% Volume Distribution (VD):   0.256
Fu: 4.625%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.0
BSEP inhibitor:   0.997

ADMET: Metabolism

CYP1A2-inhibitor:   0.321 CYP1A2-substrate:   0.841
CYP2C19-inhibitor:   0.997 CYP2C19-substrate:   0.015
CYP2C9-inhibitor:   0.992 CYP2C9-substrate:   0.001
CYP2D6-inhibitor:   0.042 CYP2D6-substrate:   0.368
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   0.898
CYP2B6-substrate:   1.0 CYP2C8-inhibitor:   0.642
HLM stability:   0.762
?
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):  4.663 Half-life (T1/2):  0.878

ADMET: Toxicity

hERG Blockers:  0.111 hERG Blockers (10um):  0.446
Human Hepatotoxicity (H-HT):  0.557 Drug-induced Liver Injury (DILI):  0.875
AMES Toxicity:  0.657 Rat Oral Acute Toxicity:  0.612
Maximum Recommended Daily Dose:  0.763 Skin Sensitization:  0.522
Carcinogencity:  0.675 Eye Corrosion:  0.032
Eye Irritation:  0.775 Respiratory Toxicity:  0.738
Drug-induced Neurotoxicity:  0.572 Ototoxicity:  0.29
Hematotoxicity:  0.242 Drug-induced Nephrotoxicity:  0.473
Genotoxicity:  0.829 RPMI-8226 Immunitoxicity:  0.087
A549 Cytotoxicity:  0.099 Hek293 Cytotoxicity:  0.416
BCF:   1.18
?
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:   3.874
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.784
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.192
?
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
NPO15394 Angelica decursiva Species Apiaceae Eukaryota n.a. root n.a. PMID[22784551]
NPO15394 Angelica decursiva Species Apiaceae Eukaryota n.a. root n.a. PMID[25068578]
NPO4340 Peucedanum praeruptorum Species Apiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15394 Angelica decursiva Species Apiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4340 Peucedanum praeruptorum Species Apiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO15394 Angelica decursiva Species Apiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO4340 Peucedanum praeruptorum Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO15394 Angelica decursiva Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO4340 Peucedanum praeruptorum Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO15394 Angelica decursiva Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO15394 Angelica decursiva Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO4340 Peucedanum praeruptorum Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO15394 Angelica decursiva Species Apiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4340 Peucedanum praeruptorum Species Apiaceae 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

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 NPC199658 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
0.8065 Intermediate Similarity NPC195357
0.8065 Intermediate Similarity NPC152771
0.6377 Remote Similarity NPC471910
0.6286 Remote Similarity NPC296624
0.5733 Remote Similarity NPC100986
0.5658 Remote Similarity NPC283019
0.5634 Remote Similarity NPC129572
0.5625 Remote Similarity NPC225106
0.5625 Remote Similarity NPC184861
0.5625 Remote Similarity NPC281014
0.5625 Remote Similarity NPC212124
0.5625 Remote Similarity NPC294456
0.5493 Remote Similarity NPC260265
0.5405 Remote Similarity NPC84894
0.5405 Remote Similarity NPC18804
0.5405 Remote Similarity NPC319859
0.5405 Remote Similarity NPC164269
0.5405 Remote Similarity NPC198381
0.5405 Remote Similarity NPC287182
0.5405 Remote Similarity NPC127888
0.5362 Remote Similarity NPC167111
0.5362 Remote Similarity NPC318400
0.5286 Remote Similarity NPC472424
0.5286 Remote Similarity NPC281241
0.527 Remote Similarity NPC195343
0.527 Remote Similarity NPC267412
0.527 Remote Similarity NPC207002
0.527 Remote Similarity NPC133956
0.527 Remote Similarity NPC74655
0.5205 Remote Similarity NPC166672
0.5205 Remote Similarity NPC86892
0.5205 Remote Similarity NPC471909
0.5195 Remote Similarity NPC471625
0.5152 Remote Similarity NPC50896
0.5152 Remote Similarity NPC326600
0.5068 Remote Similarity NPC476457
0.5067 Remote Similarity NPC149320
0.5067 Remote Similarity NPC160727
0.5067 Remote Similarity NPC177281
0.5067 Remote Similarity NPC312881

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC199658 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