Natural Product: NPC472381

Natural Product IDNPC472381
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 JWFFWURECCTPGO-DYRYEQCVSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL3397949
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0002585] O-methylated flavonoids
          • [CHEMONTID:0002593] 8-O-methylated flavonoids

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 JWFFWURECCTPGO-DYRYEQCVSA-N
Standard InCHI InChI=1S/C23H26O12/c1-31-14-7-11(27)16-10(26)6-13(33-22(16)21(14)32-2)17-9(25)4-3-5-12(17)34-23-20(30)19(29)18(28)15(8-24)35-23/h3-5,7,13,15,18-20,23-25,27-30H,6,8H2,1-2H3/t13-,15+,18+,19-,20+,23+/m0/s1
SMILES COC1=C(C2=C(C(=O)CC(O2)C3=C(C=CC=C3OC4C(C(C(C(O4)CO)O)O)O)O)C(=C1)O)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   494.14 Volume:   459.166
?
Van der Waals volume.
Dense:   1.076 LogP:   0.41
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   0.971
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.242
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   24.0
TPSA:   184.6
?
Topological Polar Surface Area.
 H-Bond Acceptor:   12.0
H-Bond Donor:   6.0 Rings:   4.0
Heavy Atoms:   12.0

MedChem Properties

QED Drug-Likeness Score:   0.316 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.286 Fsp3:   0.435
MCE-18:   92.455
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Accepted
Pfizer Rule:   Rejected GSK Rule:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.139 Fluc inhibitor:   0.004
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.196
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.733
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.074 Promiscuous compounds:   0.169

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.218 MDCK Permeability:   -5.301
Pgp-inhibitor:   0.0 Pgp-substrate:   0.317
PAMPA:   0.988
?
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):   0.43
20% Bioavailability (F20%):   0.246 30% Bioavailability (F30%):   0.763
50% Bioavailability (F50%):   0.971

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.088 MRP1:   0.975
Plasma Protein Binding (PPB):   77.271% Volume Distribution (VD):   -0.187
Fu: 22.64%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.011
OATP1B3 inhibitor:   0.878 BCRP inhibitor:   0.2
BSEP inhibitor:   0.175

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.005 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.996 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.008 CYP2D6-substrate:   0.001
CYP3A4-inhibitor:   0.266 CYP3A4-substrate:   0.007
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.001
HLM stability:   0.013
?
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):  2.314 Half-life (T1/2):  2.269

ADMET: Toxicity

hERG Blockers:  0.039 hERG Blockers (10um):  0.378
Human Hepatotoxicity (H-HT):  0.675 Drug-induced Liver Injury (DILI):  0.718
AMES Toxicity:  0.669 Rat Oral Acute Toxicity:  0.474
Maximum Recommended Daily Dose:  0.246 Skin Sensitization:  0.375
Carcinogencity:  0.417 Eye Corrosion:  0.0
Eye Irritation:  0.087 Respiratory Toxicity:  0.252
Drug-induced Neurotoxicity:  0.123 Ototoxicity:  0.949
Hematotoxicity:  0.167 Drug-induced Nephrotoxicity:  0.38
Genotoxicity:  0.448 RPMI-8226 Immunitoxicity:  0.23
A549 Cytotoxicity:  0.291 Hek293 Cytotoxicity:  0.647
BCF:   0.538
?
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:   2.996
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.873
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.765
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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
NPO20278 Scutellaria indica Species Lamiaceae Eukaryota whole plant n.a. n.a. PMID[25637363]
NPO20278 Scutellaria indica Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20278 Scutellaria indica Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO20278 Scutellaria indica Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO20278 Scutellaria indica Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO20278 Scutellaria indica Species Lamiaceae 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
NPT113 Cell line RAW264.7 Mus musculus IC50 > 30000.0 nM PMID[22582991]

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 NPC472381 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
0.7333 Intermediate Similarity NPC472383
0.6375 Remote Similarity NPC472380
0.593 Remote Similarity NPC472386
0.5833 Remote Similarity NPC472382
0.575 Remote Similarity NPC219163
0.5625 Remote Similarity NPC97052
0.561 Remote Similarity NPC181014
0.5595 Remote Similarity NPC236934
0.5556 Remote Similarity NPC39351
0.5422 Remote Similarity NPC29830
0.5366 Remote Similarity NPC26195
0.5309 Remote Similarity NPC169248
0.5309 Remote Similarity NPC72649
0.5301 Remote Similarity NPC206378
0.5269 Remote Similarity NPC472387
0.5217 Remote Similarity NPC152722
0.5181 Remote Similarity NPC471457
0.5176 Remote Similarity NPC5778
0.5135 Remote Similarity NPC23084
0.5119 Remote Similarity NPC106625
0.5116 Remote Similarity NPC477502
0.506 Remote Similarity NPC170475
0.5056 Remote Similarity NPC472384

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC472381 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