Natural Product: NPC478947

Natural Product IDNPC478947
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 ZSBXGIUJOOQZMP-RGCMKSIDSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 6350977
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000279] Alkaloids and derivatives
      • [CHEMONTID:0002719] Lupin alkaloids
        • [CHEMONTID:0002720] Matrine alkaloids

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 ZSBXGIUJOOQZMP-RGCMKSIDSA-N
Standard InCHI InChI=1S/C15H24N2O/c18-14-7-1-6-13-12-5-3-9-16-8-2-4-11(15(12)16)10-17(13)14/h11-13,15H,1-10H2/t11-,12-,13-,15-/m1/s1
SMILES C1C[C@@H]2[C@H]3CCCN4CCC[C@H](CN2C(=O)C1)[C@H]34

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   248.19 Volume:   261.918
?
Van der Waals volume.
Dense:   0.948 LogP:   1.161
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.477
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -1.742
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   0.0 Rigid Bonds:   21.0
TPSA:   23.55
?
Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   0.0 Rings:   4.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.653 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.707 Fsp3:   0.933
MCE-18:   56.345
?
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:   0.077 Fluc inhibitor:   0.001
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.046
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.019
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.012 Promiscuous compounds:   0.035

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.82 MDCK Permeability:   -4.908
Pgp-inhibitor:   0.059 Pgp-substrate:   0.365
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%):   0.0 30% Bioavailability (F30%):   0.166
50% Bioavailability (F50%):   0.033

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.969 MRP1:   0.752
Plasma Protein Binding (PPB):   26.876% Volume Distribution (VD):   0.114
Fu: 69.105%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.498
OATP1B3 inhibitor:   0.794 BCRP inhibitor:   0.02
BSEP inhibitor:   0.372

ADMET: Metabolism

CYP1A2-inhibitor:   0.624 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.201
CYP2D6-inhibitor:   0.928 CYP2D6-substrate:   0.018
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   0.357
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.0
HLM stability:   0.824
?
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):  6.905 Half-life (T1/2):  2.903

ADMET: Toxicity

hERG Blockers:  0.209 hERG Blockers (10um):  0.386
Human Hepatotoxicity (H-HT):  0.58 Drug-induced Liver Injury (DILI):  0.045
AMES Toxicity:  0.442 Rat Oral Acute Toxicity:  0.428
Maximum Recommended Daily Dose:  0.553 Skin Sensitization:  0.778
Carcinogencity:  0.698 Eye Corrosion:  0.447
Eye Irritation:  0.838 Respiratory Toxicity:  0.799
Drug-induced Neurotoxicity:  0.619 Ototoxicity:  0.333
Hematotoxicity:  0.317 Drug-induced Nephrotoxicity:  0.359
Genotoxicity:  0.721 RPMI-8226 Immunitoxicity:  0.039
A549 Cytotoxicity:  0.036 Hek293 Cytotoxicity:  0.259
BCF:   0.358
?
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:   2.726
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.125
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.233
?
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
NPT82 Cell line MDA-MB-231 Homo sapiens IC50 > 40000.0 nM PMID[26865176]
NPT91 Cell line KB Homo sapiens IC50 > 40000.0 nM PMID[26865176]
NPT81 Cell line A549 Homo sapiens IC50 > 40000.0 nM PMID[26865176]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 > 40000.0 nM PMID[26865176]
NPT963 Organism Hepatitis B virus Hepatitis B virus Inhibition = 13.8 % PMID[30298740]
NPT24647 Cell line HepG2 2.2.15 Homo sapiens GI >= 25.0 % PMID[30298740]

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 NPC478947 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 NPC266383
1.0 High Similarity NPC180401
1.0 High Similarity NPC48448
1.0 High Similarity NPC206241
0.6207 Remote Similarity NPC488181
0.6042 Remote Similarity NPC178632
0.5862 Remote Similarity NPC488180
0.5833 Remote Similarity NPC127430
0.56 Remote Similarity NPC271803
0.56 Remote Similarity NPC68043
0.56 Remote Similarity NPC290231
0.551 Remote Similarity NPC308050
0.549 Remote Similarity NPC124359
0.5385 Remote Similarity NPC488182
0.5312 Remote Similarity NPC488178
0.5312 Remote Similarity NPC488179

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC478947 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