Natural Product: NPC216795

Natural Product IDNPC216795
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 GBVCHRDRVDOMQV-RTWAWAEBSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 6708539
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0002506] Isoflavonoids
        • [CHEMONTID:0001607] Rotenoids
          • [CHEMONTID:0003528] Rotenones

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 GBVCHRDRVDOMQV-RTWAWAEBSA-N
Standard InCHI InChI=1S/C23H24O6/c1-12(2)5-6-13-16(24)8-7-14-22(25)21-15-9-18(26-3)19(27-4)10-17(15)28-11-20(21)29-23(13)14/h5,7-10,20-21,24H,6,11H2,1-4H3/t20-,21+/m1/s1
SMILES CC(=CCc1c(ccc2C(=O)[C@H]3c4cc(c(cc4OC[C@H]3Oc12)OC)OC)O)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   396.16 Volume:   403.788
?
Van der Waals volume.
Dense:   0.981 LogP:   4.004
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.291
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.271
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   23.0
TPSA:   74.22
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   1.0 Rings:   4.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.787 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.574 Fsp3:   0.348
MCE-18:   76.645
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Accepted GSK Rule:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.524 Fluc inhibitor:   0.802
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.796
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.496
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.232 Promiscuous compounds:   0.36

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.795 MDCK Permeability:   -4.685
Pgp-inhibitor:   0.444 Pgp-substrate:   0.011
PAMPA:   0.012
?
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):   0.03
20% Bioavailability (F20%):   0.974 30% Bioavailability (F30%):   0.972
50% Bioavailability (F50%):   0.998

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.003 MRP1:   0.942
Plasma Protein Binding (PPB):   92.843% Volume Distribution (VD):   0.301
Fu: 7.162%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.99
OATP1B3 inhibitor:   0.994 BCRP inhibitor:   0.975
BSEP inhibitor:   0.991

ADMET: Metabolism

CYP1A2-inhibitor:   0.19 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.999
CYP2C9-inhibitor:   0.597 CYP2C9-substrate:   0.784
CYP2D6-inhibitor:   0.994 CYP2D6-substrate:   0.988
CYP3A4-inhibitor:   0.089 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   1.0
?
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):  7.405 Half-life (T1/2):  2.268

ADMET: Toxicity

hERG Blockers:  0.088 hERG Blockers (10um):  0.516
Human Hepatotoxicity (H-HT):  0.815 Drug-induced Liver Injury (DILI):  0.975
AMES Toxicity:  0.748 Rat Oral Acute Toxicity:  0.937
Maximum Recommended Daily Dose:  0.514 Skin Sensitization:  0.997
Carcinogencity:  0.491 Eye Corrosion:  0.0
Eye Irritation:  0.56 Respiratory Toxicity:  0.989
Drug-induced Neurotoxicity:  0.848 Ototoxicity:  0.733
Hematotoxicity:  0.738 Drug-induced Nephrotoxicity:  0.949
Genotoxicity:  0.972 RPMI-8226 Immunitoxicity:  0.295
A549 Cytotoxicity:  0.861 Hek293 Cytotoxicity:  0.829
BCF:   1.682
?
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:   4.303
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.193
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.243
?
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
NPO16886 Amorpha fruticosa Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[18841906]
NPO16886 Amorpha fruticosa Species Fabaceae Eukaryota Fruits n.a. n.a. PMID[28075580]
NPO16886 Amorpha fruticosa Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[8326318]
NPO16886 Amorpha fruticosa Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[8350086]
NPO16886 Amorpha fruticosa Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16886 Amorpha fruticosa Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO16886 Amorpha fruticosa Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO16886 Amorpha fruticosa Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO16886 Amorpha fruticosa 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
NPT72 Individual protein Solute carrier organic anion transporter family member 1B3 Homo sapiens Inhibition = 99.21 % PMID[23571415]
NPT73 Individual protein Solute carrier organic anion transporter family member 1B1 Homo sapiens Inhibition = 53.2 % PMID[23571415]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT1864 Cell line L5178Y Mus musculus IC50 = 600.0 nM PMID[28075580]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 9800.0 nM PMID[23186287]
NPT2 Others Unspecified n.a. IC50 = 1090.0 nM PMID[32459967]

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 NPC216795 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
0.589 Remote Similarity NPC239374
0.589 Remote Similarity NPC298093
0.589 Remote Similarity NPC600423
0.5811 Remote Similarity NPC173292
0.5658 Remote Similarity NPC128293
0.5658 Remote Similarity NPC479307
0.5658 Remote Similarity NPC273959
0.5652 Remote Similarity NPC8636
0.5584 Remote Similarity NPC103307
0.5571 Remote Similarity NPC39195
0.5526 Remote Similarity NPC165549
0.5522 Remote Similarity NPC602167
0.5316 Remote Similarity NPC120593
0.5067 Remote Similarity NPC482703

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC216795 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
0.589 Remote Similarity NPD5494 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