Natural Product: NPC267412

Natural Product IDNPC267412
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Praeruptorin A
IUPAC Name [(9S,10S)-10-acetyloxy-8,8-dimethyl-2-oxo-9,10-dihydropyrano[2,3-f]chromen-9-yl] (Z)-2-methylbut-2-enoate
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL2376509
PubChem CID 38347607
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 XGPBRZDOJDLKOT-NXIDYTHLSA-N
Standard InCHI InChI=1S/C21H22O7/c1-6-11(2)20(24)27-19-18(25-12(3)22)16-14(28-21(19,4)5)9-7-13-8-10-15(23)26-17(13)16/h6-10,18-19H,1-5H3/b11-6-/t18-,19-/m0/s1
SMILES C/C=C(C(=O)O[C@H]1[C@@H](OC(=O)C)c2c(OC1(C)C)ccc1c2oc(=O)cc1)/C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   386.14 Volume:   386.543
?
Van der Waals volume.
Dense:   0.999 LogP:   2.212
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.352
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.129
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The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   20.0
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:   0.453 GASA:   1.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.718 Fsp3:   0.381
MCE-18:   70.552
?
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:   0.271 Fluc inhibitor:   0.033
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.856
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.576
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.326 Promiscuous compounds:   0.154

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.848 MDCK Permeability:   -4.664
Pgp-inhibitor:   0.308 Pgp-substrate:   0.0
PAMPA:   0.434
?
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%):   0.898 30% Bioavailability (F30%):   0.961
50% Bioavailability (F50%):   0.951

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   1.0
Plasma Protein Binding (PPB):   96.902% Volume Distribution (VD):   -0.018
Fu: 2.562%
?
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:   0.013 CYP1A2-substrate:   0.648
CYP2C19-inhibitor:   0.37 CYP2C19-substrate:   0.353
CYP2C9-inhibitor:   0.926 CYP2C9-substrate:   0.34
CYP2D6-inhibitor:   0.004 CYP2D6-substrate:   0.977
CYP3A4-inhibitor:   0.77 CYP3A4-substrate:   0.978
CYP2B6-substrate:   0.098 CYP2C8-inhibitor:   0.999
HLM stability:   0.998
?
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):  5.12 Half-life (T1/2):  0.594

ADMET: Toxicity

hERG Blockers:  0.028 hERG Blockers (10um):  0.197
Human Hepatotoxicity (H-HT):  0.577 Drug-induced Liver Injury (DILI):  0.893
AMES Toxicity:  0.732 Rat Oral Acute Toxicity:  0.514
Maximum Recommended Daily Dose:  0.654 Skin Sensitization:  0.747
Carcinogencity:  0.706 Eye Corrosion:  0.493
Eye Irritation:  0.948 Respiratory Toxicity:  0.459
Drug-induced Neurotoxicity:  0.068 Ototoxicity:  0.174
Hematotoxicity:  0.254 Drug-induced Nephrotoxicity:  0.269
Genotoxicity:  0.931 RPMI-8226 Immunitoxicity:  0.049
A549 Cytotoxicity:  0.064 Hek293 Cytotoxicity:  0.325
BCF:   1.332
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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:   4.188
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.338
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.782
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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]
NPO10678 Anemia phyllitidis Species Anemiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15394 Angelica decursiva Species Apiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO6020 Termitomyces titanicus Species Lyophyllaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
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]
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]
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[TM-MC]
NPO15394 Angelica decursiva Species Apiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6020 Termitomyces titanicus Species Lyophyllaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6534 Taraxacum alpinum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10678 Anemia phyllitidis Species Anemiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4340 Peucedanum praeruptorum Species Apiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9816 Polyporus porrectus Species Polyporaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8376 Dryopteris wallichiana Species Dryopteridaceae 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
NPT2 Others Unspecified n.a. IC50 = 27400.0 nM PMID[23517722]

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 NPC267412 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 NPC195343
1.0 High Similarity NPC74655
0.9492 High Similarity NPC84894
0.9492 High Similarity NPC18804
0.9492 High Similarity NPC164269
0.9492 High Similarity NPC287182
0.9167 High Similarity NPC319859
0.9167 High Similarity NPC198381
0.9167 High Similarity NPC127888
0.9032 High Similarity NPC471625
0.8889 High Similarity NPC100986
0.8615 High Similarity NPC471630
0.8448 Intermediate Similarity NPC167111
0.8448 Intermediate Similarity NPC318400
0.8095 Intermediate Similarity NPC471910
0.8065 Intermediate Similarity NPC166672
0.7903 Intermediate Similarity NPC476457
0.7812 Intermediate Similarity NPC149320
0.7812 Intermediate Similarity NPC160727
0.7812 Intermediate Similarity NPC177281
0.7778 Intermediate Similarity NPC86892
0.7692 Intermediate Similarity NPC128529
0.7692 Intermediate Similarity NPC296624
0.75 Intermediate Similarity NPC471909
0.7424 Intermediate Similarity NPC476455
0.7424 Intermediate Similarity NPC55615
0.7143 Intermediate Similarity NPC283019
0.6667 Remote Similarity NPC307412
0.6567 Remote Similarity NPC260265
0.6429 Remote Similarity NPC606124
0.6377 Remote Similarity NPC195357
0.6377 Remote Similarity NPC152771
0.6286 Remote Similarity NPC312881
0.6094 Remote Similarity NPC199204
0.5493 Remote Similarity NPC469675
0.5417 Remote Similarity NPC55149
0.5211 Remote Similarity NPC472424
0.5211 Remote Similarity NPC281241
0.5205 Remote Similarity NPC287286
0.52 Remote Similarity NPC47163
0.5143 Remote Similarity NPC153818
0.5143 Remote Similarity NPC232246

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC267412 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