Natural Product: NPC210048

Natural Product IDNPC210048
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 GPSKVSZZHKDRDQ-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1517104
PubChem CID 10342974
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0000123] Benzopyrans
        • [CHEMONTID:0003410] 1-benzopyrans
          • [CHEMONTID:0003543] Pyranochromenes

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 GPSKVSZZHKDRDQ-UHFFFAOYSA-N
Standard InCHI InChI=1S/C25H24O7/c1-13(2)7-10-24-22(28)20-19(12-17-15(21(20)27)8-9-23(3,4)30-17)32-25(24,29)16-6-5-14(26)11-18(16)31-24/h5-9,11-12,26-27,29H,10H2,1-4H3
SMILES CC(=CCC12Oc3c(C2(O)Oc2c(C1=O)c(O)c1c(c2)OC(C=C1)(C)C)ccc(c3)O)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   436.15 Volume:   435.977
?
Van der Waals volume.
Dense:   1.0 LogP:   4.049
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.04
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.529
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   27.0
TPSA:   105.45
?
Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   3.0 Rings:   5.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.606 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.373 Fsp3:   0.32
MCE-18:   108.182
?
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:   0.299 Fluc inhibitor:   0.206
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.874
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.652
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.316 Promiscuous compounds:   0.16

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.991 MDCK Permeability:   -4.746
Pgp-inhibitor:   0.541 Pgp-substrate:   0.02
PAMPA:   0.934
?
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):   0.015
20% Bioavailability (F20%):   0.915 30% Bioavailability (F30%):   0.96
50% Bioavailability (F50%):   0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.005 MRP1:   0.954
Plasma Protein Binding (PPB):   95.001% Volume Distribution (VD):   0.233
Fu: 4.908%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   0.92 BCRP inhibitor:   0.573
BSEP inhibitor:   0.973

ADMET: Metabolism

CYP1A2-inhibitor:   0.564 CYP1A2-substrate:   0.978
CYP2C19-inhibitor:   0.076 CYP2C19-substrate:   0.38
CYP2C9-inhibitor:   0.94 CYP2C9-substrate:   0.215
CYP2D6-inhibitor:   0.951 CYP2D6-substrate:   0.218
CYP3A4-inhibitor:   0.022 CYP3A4-substrate:   0.101
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.996
HLM stability:   0.98
?
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):  6.687 Half-life (T1/2):  1.353

ADMET: Toxicity

hERG Blockers:  0.075 hERG Blockers (10um):  0.479
Human Hepatotoxicity (H-HT):  0.709 Drug-induced Liver Injury (DILI):  0.288
AMES Toxicity:  0.734 Rat Oral Acute Toxicity:  0.728
Maximum Recommended Daily Dose:  0.576 Skin Sensitization:  0.781
Carcinogencity:  0.688 Eye Corrosion:  0.0
Eye Irritation:  0.472 Respiratory Toxicity:  0.766
Drug-induced Neurotoxicity:  0.244 Ototoxicity:  0.552
Hematotoxicity:  0.256 Drug-induced Nephrotoxicity:  0.494
Genotoxicity:  0.895 RPMI-8226 Immunitoxicity:  0.103
A549 Cytotoxicity:  0.23 Hek293 Cytotoxicity:  0.638
BCF:   1.724
?
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:   4.619
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.45
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.782
?
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
NPO14875 Morus cathayana Species Moraceae Eukaryota n.a. n.a. n.a. PMID[19338315]
NPO28265 Morus alba Species Moraceae Eukaryota n.a. n.a. n.a. PMID[20815207]
NPO28265 Morus alba Species Moraceae Eukaryota n.a. root n.a. PMID[21319773]
NPO28265 Morus alba Species Moraceae Eukaryota n.a. bark n.a. PMID[21319773]
NPO28265 Morus alba Species Moraceae Eukaryota n.a. leaf n.a. PMID[21319773]
NPO28265 Morus alba Species Moraceae Eukaryota n.a. leaf n.a. PMID[22207282]
NPO14875 Morus cathayana Species Moraceae Eukaryota Fruits Zhenjiang, Jiangsu Province, China PMID[23060696]
NPO28265 Morus alba Species Moraceae Eukaryota n.a. root n.a. PMID[23806866]
NPO28265 Morus alba Species Moraceae Eukaryota n.a. Konya, Turkey 2007-APR PMID[24901948]
NPO28265 Morus alba Species Moraceae Eukaryota root bark University of Veterinary and Pharmaceutical Sciences Brno (UVPS Brno), Brno, Czech Republic 2011-APR PMID[24901948]
NPO28265 Morus alba Species Moraceae Eukaryota leaves Chungbuk, Korea n.a. PMID[25935644]
NPO28265 Morus alba Species Moraceae Eukaryota n.a. root n.a. PMID[25981820]
NPO28265 Morus alba Species Moraceae Eukaryota n.a. latex n.a. PMID[27294120]
NPO28265 Morus alba Species Moraceae Eukaryota Root barks n.a. n.a. PMID[3097265]
NPO28265 Morus alba Species Moraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14875 Morus cathayana Species Moraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14875 Morus cathayana Species Moraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO28265 Morus alba Species Moraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO14875 Morus cathayana Species Moraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO28265 Morus alba Species Moraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO28265 Morus alba Species Moraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO28265 Morus alba Species Moraceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO28265 Morus alba Species Moraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14875 Morus cathayana Species Moraceae 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
NPT1254 Individual protein Streptokinase A Streptococcus pyogenes serotype M1 EC50 = 2395.0 nM PubChem BioAssay data set
NPT154 Individual protein Mothers against decapentaplegic homolog 3 Homo sapiens Potency n.a. 35481.3 nM PubChem BioAssay data set
NPT10 Individual protein Geminin Homo sapiens Potency n.a. 366.3 nM PubChem BioAssay data set
NPT101 Individual protein Glucagon-like peptide 1 receptor Homo sapiens Potency n.a. 28183.8 nM PubChem BioAssay data set
NPT159 Individual protein Aberrant vpr protein Human immunodeficiency virus 1 Potency n.a. 50118.7 nM PubChem BioAssay data set
NPT160 Individual protein TAR DNA-binding protein 43 Homo sapiens Potency n.a. 25118.9 nM PubChem BioAssay data set
NPT161 Individual protein Rap guanine nucleotide exchange factor 4 Homo sapiens Potency n.a. 89125.1 nM PubChem BioAssay data set
NPT446 Individual protein Rap guanine nucleotide exchange factor 3 Homo sapiens Potency n.a. 112201.8 nM PubChem BioAssay data set
NPT861 Individual protein Isocitrate dehydrogenase [NADP] cytoplasmic Homo sapiens Potency n.a. 50118.7 nM PubChem BioAssay data set
NPT478 Individual protein Ataxin-2 Homo sapiens Potency n.a. 28183.8 nM PubChem BioAssay data set
NPT920 Individual protein Alpha-synuclein Homo sapiens Potency n.a. 35481.3 nM PubChem BioAssay data set
NPT532 Individual protein Lysine-specific demethylase 4A Homo sapiens Potency n.a. 56234.1 nM PubChem BioAssay data set

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT65 Cell line HepG2 Homo sapiens Potency n.a. 22387.2 nM PubChem BioAssay data set
NPT174 Organism Streptococcus Streptococcus EC50 = 3916.0 nM PubChem BioAssay data set
NPT1252 Organism Streptococcus sp. 'group A' Streptococcus sp. 'group A' EC50 = 3320.0 nM PubChem BioAssay data set

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 NPC210048 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
0.5568 Remote Similarity NPC474276
0.5568 Remote Similarity NPC17105
0.5568 Remote Similarity NPC157115
0.5432 Remote Similarity NPC311574

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC210048 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