Natural Product: NPC318400

Natural Product IDNPC318400
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (9-Acetyloxy-8,8-Dimethyl-2-Oxo-9,10-Dihydropyrano[2,3-F]Chromen-10-Yl) Acetate
IUPAC Name (9-acetyloxy-8,8-dimethyl-2-oxo-9,10-dihydropyrano[2,3-f]chromen-10-yl) acetate
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL340124
PubChem CID 455806
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 YJOWXMGENDGFDH-UHFFFAOYSA-N
Standard InCHI InChI=1S/C18H18O7/c1-9(19)22-16-14-12(25-18(3,4)17(16)23-10(2)20)7-5-11-6-8-13(21)24-15(11)14/h5-8,16-17H,1-4H3
SMILES CC(=O)OC1C(C(OC2=C1C3=C(C=C2)C=CC(=O)O3)(C)C)OC(=O)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   346.11 Volume:   337.291
?
Van der Waals volume.
Dense:   1.026 LogP:   1.847
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.808
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.69
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   19.0
TPSA:   92.04
?
Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   0.0 Rings:   3.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.609 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.479 Fsp3:   0.389
MCE-18:   68.04
?
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:   0.05 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.98
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.302
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.401 Promiscuous compounds:   0.081

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.767 MDCK Permeability:   -4.608
Pgp-inhibitor:   0.405 Pgp-substrate:   0.0
PAMPA:   0.357
?
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%):   0.962 30% Bioavailability (F30%):   0.955
50% Bioavailability (F50%):   0.901

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   1.0
Plasma Protein Binding (PPB):   94.485% Volume Distribution (VD):   -0.045
Fu: 5.396%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.0
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.733
CYP2C19-inhibitor:   0.266 CYP2C19-substrate:   0.191
CYP2C9-inhibitor:   0.034 CYP2C9-substrate:   0.654
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.998
CYP3A4-inhibitor:   0.843 CYP3A4-substrate:   0.218
CYP2B6-substrate:   0.874 CYP2C8-inhibitor:   1.0
HLM stability:   1.0
?
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):  1.941 Half-life (T1/2):  0.916

ADMET: Toxicity

hERG Blockers:  0.049 hERG Blockers (10um):  0.24
Human Hepatotoxicity (H-HT):  0.503 Drug-induced Liver Injury (DILI):  0.913
AMES Toxicity:  0.7 Rat Oral Acute Toxicity:  0.439
Maximum Recommended Daily Dose:  0.613 Skin Sensitization:  0.263
Carcinogencity:  0.791 Eye Corrosion:  0.145
Eye Irritation:  0.889 Respiratory Toxicity:  0.324
Drug-induced Neurotoxicity:  0.176 Ototoxicity:  0.195
Hematotoxicity:  0.263 Drug-induced Nephrotoxicity:  0.266
Genotoxicity:  0.905 RPMI-8226 Immunitoxicity:  0.051
A549 Cytotoxicity:  0.032 Hek293 Cytotoxicity:  0.177
BCF:   1.019
?
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:   3.654
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.769
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.156
?
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
NPO4340 Peucedanum praeruptorum 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]
NPO4340 Peucedanum praeruptorum 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]
NPO4340 Peucedanum praeruptorum 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[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
NPT24 Organism Human immunodeficiency virus 1 Human immunodeficiency virus 1 EC50 = 69400.0 nM PMID[7525962]
NPT24 Organism Human immunodeficiency virus 1 Human immunodeficiency virus 1 TI = 0.4 n.a. PMID[7525962]
NPT24 Organism Human immunodeficiency virus 1 Human immunodeficiency virus 1 EC50 = 43000.0 nM PMID[7525962]
NPT24 Organism Human immunodeficiency virus 1 Human immunodeficiency virus 1 TI = 3.0 n.a. PMID[7525962]

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 NPC318400 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
1.0 High Similarity NPC167111
0.9091 High Similarity NPC166672
0.9091 High Similarity NPC86892
0.8909 High Similarity NPC476457
0.8621 High Similarity NPC128529
0.8621 High Similarity NPC319859
0.8621 High Similarity NPC476455
0.8621 High Similarity NPC198381
0.8621 High Similarity NPC127888
0.8448 Intermediate Similarity NPC195343
0.8448 Intermediate Similarity NPC267412
0.8448 Intermediate Similarity NPC149320
0.8448 Intermediate Similarity NPC160727
0.8448 Intermediate Similarity NPC177281
0.8448 Intermediate Similarity NPC74655
0.8448 Intermediate Similarity NPC471910
0.8421 Intermediate Similarity NPC471909
0.8 Intermediate Similarity NPC84894
0.8 Intermediate Similarity NPC18804
0.8 Intermediate Similarity NPC296624
0.8 Intermediate Similarity NPC164269
0.8 Intermediate Similarity NPC287182
0.8 Intermediate Similarity NPC55615
0.7619 Intermediate Similarity NPC471625
0.75 Intermediate Similarity NPC100986
0.7385 Intermediate Similarity NPC283019
0.7273 Intermediate Similarity NPC471630
0.6271 Remote Similarity NPC199204
0.5882 Remote Similarity NPC307412
0.5781 Remote Similarity NPC472424
0.5781 Remote Similarity NPC281241
0.5758 Remote Similarity NPC287286
0.5714 Remote Similarity NPC153818
0.5714 Remote Similarity NPC232246
0.5652 Remote Similarity NPC606124
0.5606 Remote Similarity NPC469675
0.5522 Remote Similarity NPC260265
0.5507 Remote Similarity NPC312881
0.5362 Remote Similarity NPC195357
0.5362 Remote Similarity NPC152771
0.5246 Remote Similarity NPC80170
0.5217 Remote Similarity NPC484113
0.5211 Remote Similarity NPC484110
0.5075 Remote Similarity NPC26954
0.5075 Remote Similarity NPC38099

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC318400 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