Natural Product: NPC24532

Natural Product IDNPC24532
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 ZJONSYFOVDKINV-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 44134699
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0000337] Flavans
          • [CHEMONTID:0003012] Flavan-3-ols
            • [CHEMONTID:0001584] Catechins
              • [CHEMONTID:0001594] Epigallocatechins

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 ZJONSYFOVDKINV-UHFFFAOYSA-N
Standard InCHI InChI=1S/C22H18O11/c23-9-5-13(25)11-7-17(33-22(31)10-1-2-12(24)20(30)18(10)28)21(32-16(11)6-9)8-3-14(26)19(29)15(27)4-8/h1-6,17,21,23-30H,7H2
SMILES c1cc(c(c(c1C(=O)OC1Cc2c(cc(cc2OC1c1cc(c(c(c1)O)O)O)O)O)O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   458.08 Volume:   425.17
?
Van der Waals volume.
Dense:   1.077 LogP:   1.726
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.604
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.582
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   24.0
TPSA:   197.37
?
Topological Polar Surface Area.
 H-Bond Acceptor:   11.0
H-Bond Donor:   8.0 Rings:   4.0
Heavy Atoms:   11.0

MedChem Properties

QED Drug-Likeness Score:   0.212 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.746 Fsp3:   0.136
MCE-18:   87.48
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Accepted
Pfizer Rule:   Rejected GSK Rule:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   1
Chelating Alert:   1 PAINS Alert:   1
Colloidal aggregators:   0.834 Fluc inhibitor:   0.921
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.555
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.341
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.68 Promiscuous compounds:   0.419

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.742 MDCK Permeability:   -4.938
Pgp-inhibitor:   0.0 Pgp-substrate:   0.011
PAMPA:   0.613
?
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):   0.025
20% Bioavailability (F20%):   0.998 30% Bioavailability (F30%):   1.0
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.009 MRP1:   0.972
Plasma Protein Binding (PPB):   91.792% Volume Distribution (VD):   -0.423
Fu: 8.008%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.993
OATP1B3 inhibitor:   0.995 BCRP inhibitor:   0.348
BSEP inhibitor:   0.003

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.979
CYP2C9-inhibitor:   0.703 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.994
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.008
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.999
HLM stability:   0.915
?
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):  5.796 Half-life (T1/2):  2.242

ADMET: Toxicity

hERG Blockers:  0.063 hERG Blockers (10um):  0.938
Human Hepatotoxicity (H-HT):  0.254 Drug-induced Liver Injury (DILI):  0.559
AMES Toxicity:  0.603 Rat Oral Acute Toxicity:  0.344
Maximum Recommended Daily Dose:  0.904 Skin Sensitization:  1.0
Carcinogencity:  0.243 Eye Corrosion:  0.001
Eye Irritation:  0.99 Respiratory Toxicity:  0.495
Drug-induced Neurotoxicity:  0.0 Ototoxicity:  0.97
Hematotoxicity:  0.002 Drug-induced Nephrotoxicity:  0.002
Genotoxicity:  0.997 RPMI-8226 Immunitoxicity:  0.003
A549 Cytotoxicity:  0.998 Hek293 Cytotoxicity:  0.736
BCF:   0.923
?
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:   3.384
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.462
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.054
?
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
NPO2211 Solanum nigrum Species Solanaceae Eukaryota Whole plant n.a. steroidal saponins PMID[16933867]
NPO28265 Morus alba Species Moraceae Eukaryota n.a. n.a. n.a. PMID[20815207]
NPO28265 Morus alba Species Moraceae Eukaryota n.a. leaf n.a. PMID[21319773]
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[22207282]
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]
NPO2211 Solanum nigrum Species Solanaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2211 Solanum nigrum Species Solanaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO28265 Morus alba Species Moraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO2211 Solanum nigrum Species Solanaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO28265 Morus alba Species Moraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO2211 Solanum nigrum Species Solanaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
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]
NPO2211 Solanum nigrum Species Solanaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO2211 Solanum nigrum Species Solanaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28265 Morus alba 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

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference

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 NPC24532 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
0.7414 Intermediate Similarity NPC291948
0.7414 Intermediate Similarity NPC104983
0.7414 Intermediate Similarity NPC250436
0.7414 Intermediate Similarity NPC300845
0.7414 Intermediate Similarity NPC88803
0.7097 Intermediate Similarity NPC38779
0.7097 Intermediate Similarity NPC114179
0.7097 Intermediate Similarity NPC68324
0.7097 Intermediate Similarity NPC289322
0.7097 Intermediate Similarity NPC156818
0.7097 Intermediate Similarity NPC160512
0.6418 Remote Similarity NPC87317
0.6324 Remote Similarity NPC603842
0.6308 Remote Similarity NPC474656
0.6029 Remote Similarity NPC601196
0.5915 Remote Similarity NPC603291
0.5775 Remote Similarity NPC53889
0.5714 Remote Similarity NPC40222
0.5714 Remote Similarity NPC268515
0.5658 Remote Similarity NPC602382
0.5616 Remote Similarity NPC100251
0.5455 Remote Similarity NPC98583
0.5395 Remote Similarity NPC65333
0.5385 Remote Similarity NPC602962

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC24532 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
0.7414 Intermediate Similarity NPD4868 Phase 3

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