Natural Product: NPC108957

Natural Product IDNPC108957
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 N-[(7R)-1,2,3,10-Tetramethoxy-9-Oxo-6,7-Dihydro-5H-Benzo[A]Heptalen-7-Yl]Acetamide
IUPAC Name N-[(7R)-1,2,3,10-tetramethoxy-9-oxo-6,7-dihydro-5H-benzo[a]heptalen-7-yl]acetamide
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL330320
PubChem CID 53278
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0004150] Hydrocarbon derivatives
      • [CHEMONTID:0001650] Tropones

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 IAKHMKGGTNLKSZ-MRXNPFEDSA-N
Standard InCHI InChI=1S/C22H25NO6/c1-12(24)23-16-8-6-13-10-19(27-3)21(28-4)22(29-5)20(13)14-7-9-18(26-2)17(25)11-15(14)16/h7,9-11,16H,6,8H2,1-5H3,(H,23,24)/t16-/m1/s1
SMILES COc1c(OC)cc2c(c1OC)c1ccc(c(=O)cc1[C@@H](CC2)N=C(O)C)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   399.17 Volume:   406.045
?
Van der Waals volume.
Dense:   0.983 LogP:   1.566
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.002
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.523
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The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   20.0
TPSA:   86.58
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Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   1.0 Rings:   3.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.609 GASA:   1.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.303 Fsp3:   0.364
MCE-18:   64.0
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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:   0.13 Fluc inhibitor:   0.22
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.45
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.302
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.005 Promiscuous compounds:   0.297

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.744 MDCK Permeability:   -4.692
Pgp-inhibitor:   0.016 Pgp-substrate:   0.732
PAMPA:   0.747
?
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):   0.034
20% Bioavailability (F20%):   0.028 30% Bioavailability (F30%):   0.026
50% Bioavailability (F50%):   0.851

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.053 MRP1:   0.993
Plasma Protein Binding (PPB):   93.901% Volume Distribution (VD):   -0.222
Fu: 5.853%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.752
OATP1B3 inhibitor:   0.99 BCRP inhibitor:   0.435
BSEP inhibitor:   0.561

ADMET: Metabolism

CYP1A2-inhibitor:   0.967 CYP1A2-substrate:   0.008
CYP2C19-inhibitor:   0.992 CYP2C19-substrate:   0.032
CYP2C9-inhibitor:   0.888 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.373 CYP2D6-substrate:   0.006
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   0.114
CYP2B6-substrate:   0.754 CYP2C8-inhibitor:   0.288
HLM stability:   0.322
?
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):  2.496 Half-life (T1/2):  1.672

ADMET: Toxicity

hERG Blockers:  0.06 hERG Blockers (10um):  0.108
Human Hepatotoxicity (H-HT):  0.999 Drug-induced Liver Injury (DILI):  0.985
AMES Toxicity:  0.808 Rat Oral Acute Toxicity:  0.543
Maximum Recommended Daily Dose:  0.933 Skin Sensitization:  0.996
Carcinogencity:  0.939 Eye Corrosion:  0.0
Eye Irritation:  0.186 Respiratory Toxicity:  0.919
Drug-induced Neurotoxicity:  0.873 Ototoxicity:  0.64
Hematotoxicity:  0.597 Drug-induced Nephrotoxicity:  0.953
Genotoxicity:  1.0 RPMI-8226 Immunitoxicity:  0.148
A549 Cytotoxicity:  0.011 Hek293 Cytotoxicity:  0.35
BCF:   0.898
?
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:   3.646
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.968
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.312
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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
NPO1559 Pinus palustris Species Pinaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7149 Dalbergia melanoxylon Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1559 Pinus palustris Species Pinaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO7149 Dalbergia melanoxylon Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO1559 Pinus palustris Species Pinaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO7149 Dalbergia melanoxylon Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO1559 Pinus palustris Species Pinaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7149 Dalbergia melanoxylon Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28554 Lepidium meyeni Species Brassicaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5644.1 Plectranthus hadiensis var. tomentosus Varieties Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18118 Lycopodiella alopecuroides Species Lycopodiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27904 Protium opacum Species Burseraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29420 Actinoplanes regularis Species Micromonosporaceae Bacteria 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
NPT210 Individual protein Thyroid stimulating hormone receptor Homo sapiens Potency = 125.9 nM PubChem BioAssay data set
NPT211 Individual protein Hypoxia-inducible factor 1 alpha Homo sapiens Potency = 199.5 nM PubChem BioAssay data set
NPT150 Individual protein Anthrax lethal factor Bacillus anthracis Potency = 63.1 nM PubChem BioAssay data set
NPT150 Individual protein Anthrax lethal factor Bacillus anthracis Potency = 199.5 nM PubChem BioAssay data set
NPT150 Individual protein Anthrax lethal factor Bacillus anthracis Potency = 125.9 nM PubChem BioAssay data set
NPT212 Individual protein Cytochrome P450 2C9 Homo sapiens Potency = 39810.7 nM PubChem BioAssay data set
NPT483 Individual protein Prelamin-A/C Homo sapiens Potency = 79.4 nM PubChem BioAssay data set
NPT518 Protein complex Tubulin Homo sapiens Tubulin binding = 32.0 % PMID[7265112]
NPT478 Individual protein Ataxin-2 Homo sapiens Potency n.a. 10000.0 nM PubChem BioAssay data set

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT2 Others Unspecified n.a. Potency = 1000.0 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 1412.5 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 22387.2 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 28183.8 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 NPC108957 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 NPC14005
1.0 High Similarity NPC226941
0.8387 Intermediate Similarity NPC189782
0.8136 Intermediate Similarity NPC44642
0.7302 Intermediate Similarity NPC66678
0.7188 Intermediate Similarity NPC202839
0.597 Remote Similarity NPC609718
0.5781 Remote Similarity NPC600354
0.5758 Remote Similarity NPC218575
0.5606 Remote Similarity NPC190931
0.5556 Remote Similarity NPC604863

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC108957 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
1.0 High Similarity NPD5089 Approved
1.0 High Similarity NPD5090 Phase 4
0.6984 Remote Similarity NPD4055 Phase 2
0.6974 Remote Similarity NPD6841 Approved
0.6974 Remote Similarity NPD6842 Approved
0.6974 Remote Similarity NPD6843 Phase 3
0.5522 Remote Similarity NPD4585 Approved

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