Natural Product: NPC485619

Natural Product IDNPC485619
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 HWMUITXPRSEDHI-IMMUGOHXSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 11796501
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0000337] Flavans
          • [CHEMONTID:0003642] 8-prenylated flavans
            • [CHEMONTID:0003508] 8-prenylated flavanones

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 HWMUITXPRSEDHI-IMMUGOHXSA-N
Standard InCHI InChI=1S/C26H30O5/c1-15(2)6-7-18(16(3)4)12-20-21(28)13-24(30-5)25-22(29)14-23(31-26(20)25)17-8-10-19(27)11-9-17/h6,8-11,13,18,23,27-28H,3,7,12,14H2,1-2,4-5H3/t18?,23-/m0/s1
SMILES CC(=CCC(Cc1c(cc(c2C(=O)C[C@@H](c3ccc(cc3)O)Oc12)OC)O)C(=C)C)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   422.21 Volume:   452.806
?
Van der Waals volume.
Dense:   0.932 LogP:   4.903
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.881
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.084
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   7.0 Rigid Bonds:   20.0
TPSA:   75.99
?
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:   0.543 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.761 Fsp3:   0.346
MCE-18:   65.4
?
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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.953 Fluc inhibitor:   0.644
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.309
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.532
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.265 Promiscuous compounds:   0.04

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.803 MDCK Permeability:   -4.635
Pgp-inhibitor:   0.683 Pgp-substrate:   0.003
PAMPA:   0.003
?
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%):   0.0 30% Bioavailability (F30%):   0.052
50% Bioavailability (F50%):   0.917

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.001 MRP1:   0.978
Plasma Protein Binding (PPB):   96.327% Volume Distribution (VD):   0.259
Fu: 2.82%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.745
OATP1B3 inhibitor:   0.993 BCRP inhibitor:   0.977
BSEP inhibitor:   0.997

ADMET: Metabolism

CYP1A2-inhibitor:   0.002 CYP1A2-substrate:   0.946
CYP2C19-inhibitor:   0.992 CYP2C19-substrate:   0.895
CYP2C9-inhibitor:   0.877 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.738 CYP2D6-substrate:   0.862
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.953
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.108
HLM stability:   0.977
?
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):  9.502 Half-life (T1/2):  0.898

ADMET: Toxicity

hERG Blockers:  0.161 hERG Blockers (10um):  0.544
Human Hepatotoxicity (H-HT):  0.841 Drug-induced Liver Injury (DILI):  0.474
AMES Toxicity:  0.401 Rat Oral Acute Toxicity:  0.799
Maximum Recommended Daily Dose:  0.76 Skin Sensitization:  0.947
Carcinogencity:  0.358 Eye Corrosion:  0.002
Eye Irritation:  0.869 Respiratory Toxicity:  0.846
Drug-induced Neurotoxicity:  0.939 Ototoxicity:  0.739
Hematotoxicity:  0.222 Drug-induced Nephrotoxicity:  0.708
Genotoxicity:  0.953 RPMI-8226 Immunitoxicity:  0.052
A549 Cytotoxicity:  0.519 Hek293 Cytotoxicity:  0.459
BCF:   1.883
?
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:   5.021
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.624
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   6.084
?
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
NPO19231 Sophora flavescens Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[10654410]
NPO19231 Sophora flavescens Species Fabaceae Eukaryota n.a. root n.a. PMID[10843587]
NPO19231 Sophora flavescens Species Fabaceae Eukaryota Roots n.a. n.a. PMID[15568770]
NPO19231 Sophora flavescens Species Fabaceae Eukaryota n.a. root n.a. PMID[16392664]
NPO19231 Sophora flavescens Species Fabaceae Eukaryota n.a. root n.a. PMID[16933887]
NPO19231 Sophora flavescens Species Fabaceae Eukaryota roots Hualien Hsien, Taiwan 2003-JUL PMID[16933887]
NPO19231 Sophora flavescens Species Fabaceae Eukaryota n.a. root n.a. PMID[17951038]
NPO19231 Sophora flavescens Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[18175961]
NPO19231 Sophora flavescens Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[24295087]
NPO19231 Sophora flavescens Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[27575476]
NPO19231 Sophora flavescens Species Fabaceae Eukaryota Roots n.a. n.a. PMID[30298740]
NPO19231 Sophora flavescens Species Fabaceae Eukaryota Roots n.a. n.a. PMID[9868163]
NPO19231 Sophora flavescens Species Fabaceae Eukaryota n.a. root n.a. Database[Article]
NPO19231 Sophora flavescens Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19231 Sophora flavescens Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO19231 Sophora flavescens Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO19231 Sophora flavescens Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO19231 Sophora flavescens Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO19231 Sophora flavescens Species Fabaceae 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
NPT79 Organism Bacillus subtilis Bacillus subtilis MIC = 10.0 ug.mL-1 PMID[10654410]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC = 10.0 ug.mL-1 PMID[10654410]
NPT17 Organism Staphylococcus epidermidis Staphylococcus epidermidis MIC = 10.0 ug.mL-1 PMID[10654410]
NPT167 Organism Propionibacterium acnes Propionibacterium acnes MIC = 10.0 ug.mL-1 PMID[10654410]
NPT2 Others Unspecified n.a. Inhibition = 7.4 % PMID[10654410]
NPT2 Others Unspecified n.a. Inhibition = 50.3 % PMID[10654410]
NPT2 Others Unspecified n.a. Inhibition = 84.4 % PMID[10654410]
NPT2 Others Unspecified n.a. Activity = 52.6 % PMID[10654410]
NPT2 Others Unspecified n.a. Activity = 85.1 % PMID[10654410]
NPT2 Others Unspecified n.a. Activity = 96.9 % PMID[10654410]

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 NPC485619 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
0.8333 Intermediate Similarity NPC77794
0.8333 Intermediate Similarity NPC225660
0.8209 Intermediate Similarity NPC235217
0.8209 Intermediate Similarity NPC485611
0.791 Intermediate Similarity NPC485618
0.7761 Intermediate Similarity NPC473014
0.7385 Intermediate Similarity NPC76338
0.7385 Intermediate Similarity NPC250242
0.6486 Remote Similarity NPC485614
0.6486 Remote Similarity NPC473013
0.6486 Remote Similarity NPC127059
0.64 Remote Similarity NPC107177
0.64 Remote Similarity NPC485612
0.6316 Remote Similarity NPC485616
0.6316 Remote Similarity NPC217149
0.6027 Remote Similarity NPC278249
0.6027 Remote Similarity NPC473015
0.6027 Remote Similarity NPC223812
0.5775 Remote Similarity NPC220998
0.5733 Remote Similarity NPC125894
0.56 Remote Similarity NPC81697
0.56 Remote Similarity NPC485615
0.5467 Remote Similarity NPC85162
0.5385 Remote Similarity NPC225153
0.5385 Remote Similarity NPC479876
0.5316 Remote Similarity NPC488428
0.5316 Remote Similarity NPC488427
0.527 Remote Similarity NPC316816
0.5224 Remote Similarity NPC177354
0.52 Remote Similarity NPC477956
0.5176 Remote Similarity NPC257166
0.5139 Remote Similarity NPC164980
0.5068 Remote Similarity NPC107572
0.5068 Remote Similarity NPC39329
0.5068 Remote Similarity NPC32739
0.5068 Remote Similarity NPC51032

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC485619 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