Natural Product: NPC86892

Natural Product IDNPC86892
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Seravshanin
IUPAC Name [(9R,10R)-9-acetyloxy-8,8-dimethyl-2-oxo-9,10-dihydropyrano[2,3-f]chromen-10-yl] 2-methylpropanoate
Synonyms Seravshanin
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL70302
PubChem CID 10317265
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 BUTUNJHEBGRWGK-QZTJIDSGSA-N
Standard InCHI InChI=1S/C20H22O7/c1-10(2)19(23)26-17-15-13(27-20(4,5)18(17)24-11(3)21)8-6-12-7-9-14(22)25-16(12)15/h6-10,17-18H,1-5H3/t17-,18-/m1/s1
SMILES CC(=O)O[C@@H]1[C@H](OC(=O)C(C)C)c2c(OC1(C)C)ccc1c2oc(=O)cc1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   374.14 Volume:   371.883
?
Van der Waals volume.
Dense:   1.006 LogP:   2.929
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.829
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.423
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 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:   0.602 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.563 Fsp3:   0.45
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:   0.322 Fluc inhibitor:   0.004
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.876
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.329
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.323 Promiscuous compounds:   0.084

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.782 MDCK Permeability:   -4.751
Pgp-inhibitor:   0.338 Pgp-substrate:   0.0
PAMPA:   0.288
?
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%):   0.609 30% Bioavailability (F30%):   0.573
50% Bioavailability (F50%):   0.759

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.003 MRP1:   1.0
Plasma Protein Binding (PPB):   95.75% Volume Distribution (VD):   0.028
Fu: 3.603%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.998
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.0
BSEP inhibitor:   0.999

ADMET: Metabolism

CYP1A2-inhibitor:   0.042 CYP1A2-substrate:   0.513
CYP2C19-inhibitor:   0.528 CYP2C19-substrate:   0.23
CYP2C9-inhibitor:   0.281 CYP2C9-substrate:   0.104
CYP2D6-inhibitor:   0.001 CYP2D6-substrate:   0.972
CYP3A4-inhibitor:   0.813 CYP3A4-substrate:   0.993
CYP2B6-substrate:   0.152 CYP2C8-inhibitor:   1.0
HLM stability:   0.982
?
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):  6.489 Half-life (T1/2):  0.462

ADMET: Toxicity

hERG Blockers:  0.055 hERG Blockers (10um):  0.277
Human Hepatotoxicity (H-HT):  0.599 Drug-induced Liver Injury (DILI):  0.959
AMES Toxicity:  0.748 Rat Oral Acute Toxicity:  0.547
Maximum Recommended Daily Dose:  0.301 Skin Sensitization:  0.768
Carcinogencity:  0.648 Eye Corrosion:  0.279
Eye Irritation:  0.817 Respiratory Toxicity:  0.513
Drug-induced Neurotoxicity:  0.267 Ototoxicity:  0.282
Hematotoxicity:  0.545 Drug-induced Nephrotoxicity:  0.637
Genotoxicity:  0.914 RPMI-8226 Immunitoxicity:  0.089
A549 Cytotoxicity:  0.153 Hek293 Cytotoxicity:  0.194
BCF:   1.265
?
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:   3.903
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.754
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.264
?
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
NPO32915 prionosciadium watsoni Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[12088423]
NPO26621 Streptomyces uncialis Species Streptomycetaceae Bacteria n.a. n.a. n.a. PMID[18646774]
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]
NPO3509 Angelica furcijuga Species Apiaceae Eukaryota roots Miyazaki prefecture, Japan n.a. PMID[9873511]
NPO23122 Trichoderma citrinoviride Species Hypocreaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4340 Peucedanum praeruptorum Species Apiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26621 Streptomyces uncialis Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO15394 Angelica decursiva Species Apiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25369 Levisticum officinale Species Apiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26365 Gomphidius glutinosus Species Gomphidiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13650 Dysidea frondosa Species Dysideidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3509 Angelica furcijuga Species Apiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25369 Levisticum officinale Species Apiaceae Eukaryota n.a. n.a. Database[FooDB]
NPO25369 Levisticum officinale Species Apiaceae Eukaryota Seed n.a. n.a. Database[FooDB]
NPO25369 Levisticum officinale Species Apiaceae Eukaryota Root n.a. n.a. Database[FooDB]
NPO25369 Levisticum officinale Species Apiaceae Eukaryota Plant n.a. n.a. Database[FooDB]
NPO25369 Levisticum officinale Species Apiaceae Eukaryota Fruit n.a. n.a. Database[FooDB]
NPO25369 Levisticum officinale Species Apiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO3509 Angelica furcijuga Species Apiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
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]
NPO25369 Levisticum officinale Species Apiaceae Eukaryota n.a. n.a. Database[Phenol-Explorer]
NPO15394 Angelica decursiva Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO3509 Angelica furcijuga Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO25369 Levisticum officinale Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
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[TCM_Taiwan]
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[TM-MC]
NPO4340 Peucedanum praeruptorum Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO26830 Hyaena hyaena Species Hyaenidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25369 Levisticum officinale Species Apiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15394 Angelica decursiva Species Apiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23122 Trichoderma citrinoviride Species Hypocreaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4340 Peucedanum praeruptorum Species Apiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13650 Dysidea frondosa Species Dysideidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26365 Gomphidius glutinosus Species Gomphidiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26092 Agathosma abrupta Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8094 Cotoneaster veitchii Species Rosaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3509 Angelica furcijuga Species Apiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9129 Ircinia campana Species Irciniidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26621 Streptomyces uncialis Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO26014 Amphidinium corpulentum Species Gymnodiniaceae 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
NPT965 Organism Amaranthus hypochondriacus Amaranthus hypochondriacus IC50 = 402000.0 nM PMID[12088423]
NPT117 Organism Echinochloa crus-galli Echinochloa crus-galli IC50 = 162000.0 nM PMID[12088423]

In vivo activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT32 Organism Mus musculus Mus musculus IC50 = 4200.0 nM PMID[9873511]
NPT29 Organism Rattus norvegicus Rattus norvegicus IC50 > 100000.0 nM PMID[9873511]
NPT29 Organism Rattus norvegicus Rattus norvegicus Inhibition = -2.2 % PMID[9873511]





 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 NPC86892 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
0.9298 High Similarity NPC471909
0.9091 High Similarity NPC167111
0.9091 High Similarity NPC318400
0.8833 High Similarity NPC476455
0.8644 High Similarity NPC166672
0.8525 High Similarity NPC128529
0.8413 Intermediate Similarity NPC471625
0.8167 Intermediate Similarity NPC476457
0.8065 Intermediate Similarity NPC149320
0.8065 Intermediate Similarity NPC160727
0.8065 Intermediate Similarity NPC177281
0.7937 Intermediate Similarity NPC319859
0.7937 Intermediate Similarity NPC198381
0.7937 Intermediate Similarity NPC55615
0.7937 Intermediate Similarity NPC127888
0.7778 Intermediate Similarity NPC195343
0.7778 Intermediate Similarity NPC267412
0.7778 Intermediate Similarity NPC74655
0.7778 Intermediate Similarity NPC471910
0.75 Intermediate Similarity NPC471630
0.7385 Intermediate Similarity NPC84894
0.7385 Intermediate Similarity NPC18804
0.7385 Intermediate Similarity NPC296624
0.7385 Intermediate Similarity NPC164269
0.7385 Intermediate Similarity NPC287182
0.7101 Intermediate Similarity NPC283019
0.6957 Remote Similarity NPC100986
0.6269 Remote Similarity NPC287286
0.6061 Remote Similarity NPC472424
0.6061 Remote Similarity NPC281241
0.5781 Remote Similarity NPC199204
0.5479 Remote Similarity NPC307412
0.5294 Remote Similarity NPC153818
0.5294 Remote Similarity NPC232246
0.527 Remote Similarity NPC606124
0.5211 Remote Similarity NPC469675
0.5205 Remote Similarity NPC195357
0.5205 Remote Similarity NPC152771
0.5139 Remote Similarity NPC260265
0.5135 Remote Similarity NPC312881
0.5068 Remote Similarity NPC484113

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC86892 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