Natural Product: NPC281014

Natural Product IDNPC281014
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (9S,10R)-9,10-Dihydroxy-8,8-Dimethyl-9,10-Dihydropyrano[2,3-F]Chromen-2-One
IUPAC Name (9S,10R)-9,10-dihydroxy-8,8-dimethyl-9,10-dihydropyrano[2,3-f]chromen-2-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1452260
PubChem CID 11436940
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 HKXQUNNSKMWIKJ-YPMHNXCESA-N
Standard InCHI InChI=1S/C14H14O5/c1-14(2)13(17)11(16)10-8(19-14)5-3-7-4-6-9(15)18-12(7)10/h3-6,11,13,16-17H,1-2H3/t11-,13+/m1/s1
SMILES CC1(C)[C@H]([C@@H](c2c(ccc3ccc(=O)oc23)O1)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   262.08 Volume:   255.8
?
Van der Waals volume.
Dense:   1.025 LogP:   1.089
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.452
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.259
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   0.0 Rigid Bonds:   17.0
TPSA:   79.9
?
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:   0.701 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.447 Fsp3:   0.357
MCE-18:   63.0
?
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:   0.579 Fluc inhibitor:   0.092
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.973
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.125
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.323 Promiscuous compounds:   0.371

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.994 MDCK Permeability:   -4.591
Pgp-inhibitor:   0.007 Pgp-substrate:   0.001
PAMPA:   0.535
?
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):   0.001
20% Bioavailability (F20%):   0.79 30% Bioavailability (F30%):   0.88
50% Bioavailability (F50%):   0.803

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.002 MRP1:   0.998
Plasma Protein Binding (PPB):   84.148% Volume Distribution (VD):   0.245
Fu: 17.552%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.996
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.0
BSEP inhibitor:   0.993

ADMET: Metabolism

CYP1A2-inhibitor:   0.016 CYP1A2-substrate:   0.012
CYP2C19-inhibitor:   0.134 CYP2C19-substrate:   0.009
CYP2C9-inhibitor:   0.443 CYP2C9-substrate:   0.006
CYP2D6-inhibitor:   0.007 CYP2D6-substrate:   0.016
CYP3A4-inhibitor:   0.619 CYP3A4-substrate:   0.396
CYP2B6-substrate:   0.263 CYP2C8-inhibitor:   0.703
HLM stability:   0.714
?
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):  8.594 Half-life (T1/2):  1.511

ADMET: Toxicity

hERG Blockers:  0.059 hERG Blockers (10um):  0.233
Human Hepatotoxicity (H-HT):  0.507 Drug-induced Liver Injury (DILI):  0.749
AMES Toxicity:  0.749 Rat Oral Acute Toxicity:  0.292
Maximum Recommended Daily Dose:  0.372 Skin Sensitization:  0.518
Carcinogencity:  0.597 Eye Corrosion:  0.044
Eye Irritation:  0.945 Respiratory Toxicity:  0.557
Drug-induced Neurotoxicity:  0.078 Ototoxicity:  0.381
Hematotoxicity:  0.219 Drug-induced Nephrotoxicity:  0.412
Genotoxicity:  0.68 RPMI-8226 Immunitoxicity:  0.061
A549 Cytotoxicity:  0.04 Hek293 Cytotoxicity:  0.196
BCF:   0.489
?
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:   3.191
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.84
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.024
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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
NPT135 Individual protein Chromobox protein homolog 1 Homo sapiens Potency n.a. 112201.8 nM PubChem BioAssay data set
NPT7 Individual protein Thioredoxin reductase 1, cytoplasmic Rattus norvegicus Potency n.a. 25118.9 nM PubChem BioAssay data set
NPT864 Individual protein Lethal(3)malignant brain tumor-like protein 1 Homo sapiens Potency = 1995.3 nM PubChem BioAssay data set
NPT64 Individual protein ATPase family AAA domain-containing protein 5 Homo sapiens Potency n.a. 12990.0 nM PubChem BioAssay data set

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT6 Organism Plasmodium falciparum Plasmodium falciparum Potency n.a. 6573.3 nM PubChem BioAssay data set
NPT6 Organism Plasmodium falciparum Plasmodium falciparum Potency n.a. 11689.1 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 39810.7 nM PubChem BioAssay data set

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 NPC281014 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 NPC225106
1.0 High Similarity NPC184861
1.0 High Similarity NPC212124
1.0 High Similarity NPC294456
0.6792 Remote Similarity NPC188380
0.6792 Remote Similarity NPC224543
0.6604 Remote Similarity NPC50896
0.6604 Remote Similarity NPC326600
0.6333 Remote Similarity NPC287286
0.6316 Remote Similarity NPC153818
0.6316 Remote Similarity NPC232246
0.625 Remote Similarity NPC76753
0.6 Remote Similarity NPC229916
0.5714 Remote Similarity NPC104796
0.5625 Remote Similarity NPC195357
0.5625 Remote Similarity NPC152771
0.5614 Remote Similarity NPC62366
0.5538 Remote Similarity NPC312881
0.5439 Remote Similarity NPC13007
0.5439 Remote Similarity NPC610664
0.5362 Remote Similarity NPC471764
0.5357 Remote Similarity NPC175159
0.5345 Remote Similarity NPC185066
0.5345 Remote Similarity NPC33986
0.5263 Remote Similarity NPC80170
0.5263 Remote Similarity NPC472516
0.5246 Remote Similarity NPC479313
0.5211 Remote Similarity NPC469701
0.5156 Remote Similarity NPC479311
0.5143 Remote Similarity NPC169510
0.5079 Remote Similarity NPC26954
0.5079 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 NPC281014 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