Natural Product: NPC272016

Natural Product IDNPC272016
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 KUEXEFAECRHRKN-UHFFFAOYSA-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]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000145] Coumarins and derivatives
        • [CHEMONTID:0000358] Furanocoumarins

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 KUEXEFAECRHRKN-UHFFFAOYSA-N
Standard InCHI InChI=1S/C16H16O5/c1-16(2)14(21-16)8-19-11-3-4-18-13-7-12-9(5-10(11)13)6-15(17)20-12/h3,5,7,14H,4,6,8H2,1-2H3
SMILES CC1(C)C(COC2=CCOc3cc4c(cc23)CC(=O)O4)O1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   288.1 Volume:   281.835
?
Van der Waals volume.
Dense:   1.022 LogP:   2.111
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.157
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.981
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   19.0
TPSA:   57.29
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   0.0 Rings:   4.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.484 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.848 Fsp3:   0.438
MCE-18:   73.652
?
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:   0.118 Fluc inhibitor:   0.105
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.581
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.122
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.341 Promiscuous compounds:   0.225

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.658 MDCK Permeability:   -4.485
Pgp-inhibitor:   0.043 Pgp-substrate:   0.067
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):   0.0
20% Bioavailability (F20%):   0.002 30% Bioavailability (F30%):   0.0
50% Bioavailability (F50%):   0.051

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.903 MRP1:   0.986
Plasma Protein Binding (PPB):   71.289% Volume Distribution (VD):   -0.167
Fu: 28.785%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.089
OATP1B3 inhibitor:   0.573 BCRP inhibitor:   0.003
BSEP inhibitor:   0.943

ADMET: Metabolism

CYP1A2-inhibitor:   0.413 CYP1A2-substrate:   0.991
CYP2C19-inhibitor:   0.09 CYP2C19-substrate:   0.672
CYP2C9-inhibitor:   0.002 CYP2C9-substrate:   0.288
CYP2D6-inhibitor:   0.007 CYP2D6-substrate:   0.175
CYP3A4-inhibitor:   0.082 CYP3A4-substrate:   0.032
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.187
HLM stability:   0.548
?
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):  6.457 Half-life (T1/2):  1.373

ADMET: Toxicity

hERG Blockers:  0.129 hERG Blockers (10um):  0.41
Human Hepatotoxicity (H-HT):  0.609 Drug-induced Liver Injury (DILI):  0.846
AMES Toxicity:  0.741 Rat Oral Acute Toxicity:  0.669
Maximum Recommended Daily Dose:  0.644 Skin Sensitization:  0.827
Carcinogencity:  0.826 Eye Corrosion:  0.006
Eye Irritation:  0.782 Respiratory Toxicity:  0.32
Drug-induced Neurotoxicity:  0.733 Ototoxicity:  0.33
Hematotoxicity:  0.542 Drug-induced Nephrotoxicity:  0.422
Genotoxicity:  0.951 RPMI-8226 Immunitoxicity:  0.111
A549 Cytotoxicity:  0.11 Hek293 Cytotoxicity:  0.229
BCF:   1.088
?
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:   3.522
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.338
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.405
?
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
NPO24758 Angelica dahurica Species Apiaceae Eukaryota n.a. root n.a. DOI[10.5012/bkcs.2003.24.11.1699]
NPO22550 Paeonia suffruticosa Species Paeoniaceae Eukaryota n.a. n.a. n.a. PMID[11339628]
NPO24758 Angelica dahurica Species Apiaceae Eukaryota n.a. root n.a. PMID[12510838]
NPO24758 Angelica dahurica Species Apiaceae Eukaryota n.a. root n.a. PMID[15646793]
NPO22550 Paeonia suffruticosa Species Paeoniaceae Eukaryota n.a. bark n.a. PMID[17260795]
NPO22550 Paeonia suffruticosa Species Paeoniaceae Eukaryota n.a. Daejeon, Korea 2007-Jan PMID[19670875]
NPO22550 Paeonia suffruticosa Species Paeoniaceae Eukaryota n.a. seed n.a. PMID[20822014]
NPO24758 Angelica dahurica Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[21625478]
NPO24758 Angelica dahurica Species Apiaceae Eukaryota n.a. root n.a. PMID[21657081]
NPO22550 Paeonia suffruticosa Species Paeoniaceae Eukaryota n.a. root n.a. PMID[22547314]
NPO19352 Paeonia obovata Species Paeoniaceae Eukaryota n.a. seed n.a. PMID[23497864]
NPO22550 Paeonia suffruticosa Species Paeoniaceae Eukaryota root bark Bozhou, Anhui Province, China 2010-AUG PMID[24377852]
NPO22550 Paeonia suffruticosa Species Paeoniaceae Eukaryota n.a. flower n.a. PMID[24504864]
NPO22550 Paeonia suffruticosa Species Paeoniaceae Eukaryota Flowers LuoYang, HeNan, China n.a. PMID[24621197]
NPO24758 Angelica dahurica Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[27444348]
NPO24758 Angelica dahurica Species Apiaceae Eukaryota Roots n.a. n.a. PMID[31464439]
NPO29741 Paeonia moutan Species Paeoniaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO22550 Paeonia suffruticosa Species Paeoniaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19352 Paeonia obovata Species Paeoniaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29741 Paeonia moutan Species Paeoniaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO19352 Paeonia obovata Species Paeoniaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO24758 Angelica dahurica Species Apiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO19352 Paeonia obovata Species Paeoniaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO22550 Paeonia suffruticosa Species Paeoniaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO24758 Angelica dahurica Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO29741 Paeonia moutan Species Paeoniaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO22550 Paeonia suffruticosa Species Paeoniaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO24758 Angelica dahurica Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO22550 Paeonia suffruticosa Species Paeoniaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO24758 Angelica dahurica Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO19352 Paeonia obovata Species Paeoniaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22550 Paeonia suffruticosa Species Paeoniaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24758 Angelica dahurica 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 NPC272016 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
NPC

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC272016 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