Natural Product: NPC167205

Natural Product IDNPC167205
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 HHNXXWDNZKAGHV-XVNBXDOJSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 42607560
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0003467] Linear 1,3-diarylpropanoids
        • [CHEMONTID:0001630] Chalcones and dihydrochalcones
          • [CHEMONTID:0003472] 2'-Hydroxychalcones

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 HHNXXWDNZKAGHV-XVNBXDOJSA-N
Standard InCHI InChI=1S/C15H12O5/c16-10-4-1-9(2-5-10)3-7-12(17)11-6-8-13(18)15(20)14(11)19/h1-8,16,18-20H/b7-3+
SMILES c1cc(ccc1/C=C/C(=O)c1ccc(c(c1O)O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   272.07 Volume:   273.743
?
Van der Waals volume.
Dense:   0.994 LogP:   2.095
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.091
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.277
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   14.0
TPSA:   97.99
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   4.0 Rings:   2.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.391 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.233 Fsp3:   0.0
MCE-18:   13.0
?
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:   1
Chelating Alert:   1 PAINS Alert:   1
Colloidal aggregators:   0.979 Fluc inhibitor:   1.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.531
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.45
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.963 Promiscuous compounds:   0.784

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.115 MDCK Permeability:   -4.821
Pgp-inhibitor:   0.045 Pgp-substrate:   0.004
PAMPA:   0.345
?
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):   0.01
20% Bioavailability (F20%):   0.933 30% Bioavailability (F30%):   0.963
50% Bioavailability (F50%):   0.995

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.003 MRP1:   0.097
Plasma Protein Binding (PPB):   97.473% Volume Distribution (VD):   -0.671
Fu: 1.593%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.992
OATP1B3 inhibitor:   0.995 BCRP inhibitor:   0.399
BSEP inhibitor:   0.554

ADMET: Metabolism

CYP1A2-inhibitor:   0.001 CYP1A2-substrate:   0.593
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.591
CYP2C9-inhibitor:   0.014 CYP2C9-substrate:   0.789
CYP2D6-inhibitor:   0.827 CYP2D6-substrate:   0.997
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.491
?
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):  11.207 Half-life (T1/2):  1.424

ADMET: Toxicity

hERG Blockers:  0.155 hERG Blockers (10um):  0.693
Human Hepatotoxicity (H-HT):  0.449 Drug-induced Liver Injury (DILI):  0.435
AMES Toxicity:  0.413 Rat Oral Acute Toxicity:  0.124
Maximum Recommended Daily Dose:  0.636 Skin Sensitization:  0.994
Carcinogencity:  0.183 Eye Corrosion:  0.257
Eye Irritation:  0.997 Respiratory Toxicity:  0.408
Drug-induced Neurotoxicity:  0.092 Ototoxicity:  0.46
Hematotoxicity:  0.026 Drug-induced Nephrotoxicity:  0.03
Genotoxicity:  0.83 RPMI-8226 Immunitoxicity:  0.011
A549 Cytotoxicity:  0.755 Hek293 Cytotoxicity:  0.489
BCF:   1.146
?
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:   3.82
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.843
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.532
?
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
NPO25653 Spatholobus suberectus Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[26690274]
NPO25653 Spatholobus suberectus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25653 Spatholobus suberectus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO25653 Spatholobus suberectus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO25653 Spatholobus suberectus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO25653 Spatholobus suberectus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO25653 Spatholobus suberectus 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
NPT83 Cell line MCF7 Homo sapiens IC50 > 10000.0 nM PMID[26690274]
NPT82 Cell line MDA-MB-231 Homo sapiens IC50 > 10000.0 nM PMID[26690274]

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 NPC167205 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
0.8 Intermediate Similarity NPC34070
0.7442 Intermediate Similarity NPC469526
0.6829 Remote Similarity NPC19174
0.6829 Remote Similarity NPC115159
0.625 Remote Similarity NPC17525
0.6136 Remote Similarity NPC122793
0.6 Remote Similarity NPC26697
0.5778 Remote Similarity NPC297186
0.5682 Remote Similarity NPC73532
0.5625 Remote Similarity NPC205468
0.549 Remote Similarity NPC72158
0.5306 Remote Similarity NPC262359
0.5283 Remote Similarity NPC44960
0.5227 Remote Similarity NPC267552
0.5208 Remote Similarity NPC192304
0.5208 Remote Similarity NPC13238
0.5192 Remote Similarity NPC30501
0.5185 Remote Similarity NPC213485
0.5102 Remote Similarity NPC257756
0.5102 Remote Similarity NPC336114
0.5091 Remote Similarity NPC65005
0.5091 Remote Similarity NPC479645
0.5091 Remote Similarity NPC168105
0.5091 Remote Similarity NPC479648

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC167205 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