Natural Product: NPC485612

Natural Product IDNPC485612
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 YLTPWCZXKJSORQ-ODOSRFNGSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 10410874
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 YLTPWCZXKJSORQ-ODOSRFNGSA-N
Standard InCHI InChI=1S/C26H30O6/c1-14(2)6-7-16(15(3)4)10-19-20(28)12-21(29)25-22(30)13-24(32-26(19)25)18-9-8-17(27)11-23(18)31-5/h6,8-9,11-12,16,24,27-29H,3,7,10,13H2,1-2,4-5H3/t16?,24-/m0/s1
SMILES CC(=CCC(Cc1c(cc(c2C(=O)C[C@@H](c3ccc(cc3OC)O)Oc12)O)O)C(=C)C)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   438.2 Volume:   461.596
?
Van der Waals volume.
Dense:   0.949 LogP:   5.001
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.81
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.174
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   7.0 Rigid Bonds:   20.0
TPSA:   96.22
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   3.0 Rings:   3.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.486 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.906 Fsp3:   0.346
MCE-18:   68.514
?
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:   0.923 Fluc inhibitor:   0.649
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.259
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.728
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.308 Promiscuous compounds:   0.044

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.904 MDCK Permeability:   -4.703
Pgp-inhibitor:   0.072 Pgp-substrate:   0.008
PAMPA:   0.001
?
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%):   0.008 30% Bioavailability (F30%):   0.171
50% Bioavailability (F50%):   0.988

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.196 MRP1:   0.993
Plasma Protein Binding (PPB):   95.325% Volume Distribution (VD):   0.62
Fu: 3.813%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.958
OATP1B3 inhibitor:   0.983 BCRP inhibitor:   0.815
BSEP inhibitor:   0.961

ADMET: Metabolism

CYP1A2-inhibitor:   0.001 CYP1A2-substrate:   0.929
CYP2C19-inhibitor:   0.422 CYP2C19-substrate:   0.654
CYP2C9-inhibitor:   0.476 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.182 CYP2D6-substrate:   0.394
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.932
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.948
HLM stability:   0.974
?
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):  5.232 Half-life (T1/2):  1.481

ADMET: Toxicity

hERG Blockers:  0.064 hERG Blockers (10um):  0.478
Human Hepatotoxicity (H-HT):  0.795 Drug-induced Liver Injury (DILI):  0.69
AMES Toxicity:  0.677 Rat Oral Acute Toxicity:  0.825
Maximum Recommended Daily Dose:  0.799 Skin Sensitization:  0.972
Carcinogencity:  0.617 Eye Corrosion:  0.001
Eye Irritation:  0.871 Respiratory Toxicity:  0.941
Drug-induced Neurotoxicity:  0.843 Ototoxicity:  0.733
Hematotoxicity:  0.189 Drug-induced Nephrotoxicity:  0.799
Genotoxicity:  0.982 RPMI-8226 Immunitoxicity:  0.105
A549 Cytotoxicity:  0.78 Hek293 Cytotoxicity:  0.624
BCF:   1.966
?
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:   5.005
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.544
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.923
?
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 = 2.5 ug.mL-1 PMID[10654410]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC = 2.5 ug.mL-1 PMID[10654410]
NPT17 Organism Staphylococcus epidermidis Staphylococcus epidermidis MIC = 5.0 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 = 54.4 % PMID[10654410]
NPT2 Others Unspecified n.a. Inhibition = 87.1 % PMID[10654410]
NPT2 Others Unspecified n.a. Inhibition = 97.1 % PMID[10654410]
NPT2 Others Unspecified n.a. Activity = 81.7 % PMID[10654410]
NPT2 Others Unspecified n.a. Activity = 99.8 % PMID[10654410]
NPT2 Others Unspecified n.a. Activity = 93.8 % 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 NPC485612 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 NPC107177
0.7887 Intermediate Similarity NPC285630
0.7857 Intermediate Similarity NPC473013
0.7857 Intermediate Similarity NPC235217
0.7857 Intermediate Similarity NPC485611
0.7647 Intermediate Similarity NPC278249
0.7647 Intermediate Similarity NPC223812
0.7143 Intermediate Similarity NPC81697
0.7143 Intermediate Similarity NPC485615
0.7 Intermediate Similarity NPC85162
0.6533 Remote Similarity NPC77794
0.6533 Remote Similarity NPC225660
0.64 Remote Similarity NPC485619
0.6 Remote Similarity NPC473015
0.5974 Remote Similarity NPC485618
0.5974 Remote Similarity NPC485617
0.5921 Remote Similarity NPC131579
0.5921 Remote Similarity NPC125894
0.5921 Remote Similarity NPC485613
0.5844 Remote Similarity NPC473014
0.5769 Remote Similarity NPC216035
0.5584 Remote Similarity NPC301276
0.5513 Remote Similarity NPC131568
0.5479 Remote Similarity NPC324436
0.5479 Remote Similarity NPC78
0.5479 Remote Similarity NPC107572
0.5479 Remote Similarity NPC32739
0.5375 Remote Similarity NPC473016
0.5325 Remote Similarity NPC161506
0.5325 Remote Similarity NPC485620
0.5301 Remote Similarity NPC485616
0.5301 Remote Similarity NPC217149
0.52 Remote Similarity NPC148757
0.5195 Remote Similarity NPC477956
0.5125 Remote Similarity NPC166934
0.5067 Remote Similarity NPC306829
0.506 Remote Similarity NPC485614
0.506 Remote Similarity NPC127059

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC485612 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