Natural Product: NPC122793

Natural Product IDNPC122793
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 NMANELLSWUVZNL-XVNBXDOJSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 5980988
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 NMANELLSWUVZNL-XVNBXDOJSA-N
Standard InCHI InChI=1S/C15H12O4/c16-11-4-1-10(2-5-11)3-7-14(18)13-9-12(17)6-8-15(13)19/h1-9,16-17,19H/b7-3+
SMILES c1cc(ccc1/C=C/C(=O)c1cc(ccc1O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   256.07 Volume:   264.953
?
Van der Waals volume.
Dense:   0.966 LogP:   2.498
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.537
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.317
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   14.0
TPSA:   77.76
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   3.0 Rings:   2.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.448 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.076 Fsp3:   0.0
MCE-18:   12.0
?
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:   0 PAINS Alert:   0
Colloidal aggregators:   0.921 Fluc inhibitor:   1.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.576
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.401
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.987 Promiscuous compounds:   0.437

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.838 MDCK Permeability:   -4.79
Pgp-inhibitor:   0.226 Pgp-substrate:   0.001
PAMPA:   0.212
?
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):   0.003
20% Bioavailability (F20%):   0.945 30% Bioavailability (F30%):   0.975
50% Bioavailability (F50%):   0.992

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.003
Plasma Protein Binding (PPB):   97.14% Volume Distribution (VD):   -0.249
Fu: 2.763%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.989
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.568
BSEP inhibitor:   0.997

ADMET: Metabolism

CYP1A2-inhibitor:   0.048 CYP1A2-substrate:   0.996
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.964
CYP2C9-inhibitor:   0.077 CYP2C9-substrate:   0.951
CYP2D6-inhibitor:   0.914 CYP2D6-substrate:   0.268
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.319
?
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):  14.607 Half-life (T1/2):  1.305

ADMET: Toxicity

hERG Blockers:  0.142 hERG Blockers (10um):  0.488
Human Hepatotoxicity (H-HT):  0.52 Drug-induced Liver Injury (DILI):  0.181
AMES Toxicity:  0.354 Rat Oral Acute Toxicity:  0.127
Maximum Recommended Daily Dose:  0.632 Skin Sensitization:  0.89
Carcinogencity:  0.189 Eye Corrosion:  0.172
Eye Irritation:  0.996 Respiratory Toxicity:  0.648
Drug-induced Neurotoxicity:  0.448 Ototoxicity:  0.14
Hematotoxicity:  0.045 Drug-induced Nephrotoxicity:  0.175
Genotoxicity:  0.747 RPMI-8226 Immunitoxicity:  0.071
A549 Cytotoxicity:  0.282 Hek293 Cytotoxicity:  0.755
BCF:   1.248
?
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:   3.976
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.646
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.276
?
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
NPT68 Individual protein Aldose reductase Rattus norvegicus IC50 = 5390.0 nM DOI[10.1007/s00044-012-0367-5]
NPT409 Protein complex Neuronal acetylcholine receptor; alpha4/beta2 Homo sapiens Activity = 87.0 % PMID[25232969]
NPT410 Individual protein Neuronal acetylcholine receptor protein alpha-7 subunit Homo sapiens EC50 = 56000.0 nM PMID[25232969]
NPT410 Individual protein Neuronal acetylcholine receptor protein alpha-7 subunit Homo sapiens EC50 = 25000.0 nM PMID[25232969]
NPT410 Individual protein Neuronal acetylcholine receptor protein alpha-7 subunit Homo sapiens Ratio = 33.0 n.a. PMID[25232969]
NPT410 Individual protein Neuronal acetylcholine receptor protein alpha-7 subunit Homo sapiens Activity = 1258.0 % PMID[25232969]
NPT411 Protein complex Neuronal acetylcholine receptor; alpha3/beta4 Homo sapiens Activity = 83.0 % PMID[25232969]

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 NPC122793 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
0.7442 Intermediate Similarity NPC605344
0.7 Intermediate Similarity NPC19174
0.7 Intermediate Similarity NPC115159
0.6512 Remote Similarity NPC26697
0.641 Remote Similarity NPC17525
0.619 Remote Similarity NPC73532
0.6136 Remote Similarity NPC167205
0.6087 Remote Similarity NPC205468
0.6 Remote Similarity NPC13238
0.5909 Remote Similarity NPC297186
0.56 Remote Similarity NPC72158
0.56 Remote Similarity NPC30501
0.5577 Remote Similarity NPC213485
0.5435 Remote Similarity NPC34070
0.5417 Remote Similarity NPC262359
0.5385 Remote Similarity NPC44960
0.5349 Remote Similarity NPC482707
0.5349 Remote Similarity NPC267552
0.5319 Remote Similarity NPC192304
0.5306 Remote Similarity NPC284556
0.5283 Remote Similarity NPC188879
0.5208 Remote Similarity NPC257756
0.5208 Remote Similarity NPC269414
0.5208 Remote Similarity NPC336114
0.52 Remote Similarity NPC119660
0.52 Remote Similarity NPC263670
0.52 Remote Similarity NPC129132
0.5185 Remote Similarity NPC269694
0.5185 Remote Similarity NPC65005
0.5185 Remote Similarity NPC479645
0.5185 Remote Similarity NPC479648
0.5116 Remote Similarity NPC603691
0.5111 Remote Similarity NPC158222
0.5102 Remote Similarity NPC469526
0.5098 Remote Similarity NPC144281
0.5094 Remote Similarity NPC169250
0.5094 Remote Similarity NPC194764
0.5094 Remote Similarity NPC59319
0.5091 Remote Similarity NPC147688
0.5091 Remote Similarity NPC485637

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC122793 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