Natural Product: NPC19724

Natural Product IDNPC19724
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 KJXSIXMJHKAJOD-LSDHHAIUSA-M
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 25244375
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 KJXSIXMJHKAJOD-LSDHHAIUSA-M
Standard InCHI InChI=1S/C15H12O8/c16-6-3-7(17)11-10(4-6)23-15(14(22)13(11)21)5-1-8(18)12(20)9(19)2-5/h1-4,14-20,22H/p-1/t14-,15+/m0/s1
SMILES c1c(cc(c(c1O)O)O)[C@@H]1[C@H](C(=O)c2c(cc(cc2O1)[O-])O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   320.05 Volume:   294.193
?
Van der Waals volume.
Dense:   1.088 LogP:   0.625
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   0.961
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.014
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   18.0
TPSA:   147.68
?
Topological Polar Surface Area.
 H-Bond Acceptor:   8.0
H-Bond Donor:   6.0 Rings:   3.0
Heavy Atoms:   8.0

MedChem Properties

QED Drug-Likeness Score:   0.424 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.534 Fsp3:   0.133
MCE-18:   64.706
?
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:   0.814 Fluc inhibitor:   0.372
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.134
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.17
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.618 Promiscuous compounds:   0.626

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.389 MDCK Permeability:   -4.958
Pgp-inhibitor:   0.001 Pgp-substrate:   0.039
PAMPA:   0.952
?
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):   0.232
20% Bioavailability (F20%):   0.876 30% Bioavailability (F30%):   0.998
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.001 MRP1:   0.921
Plasma Protein Binding (PPB):   92.908% Volume Distribution (VD):   -0.325
Fu: 7.339%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.995
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   0.842
BSEP inhibitor:   0.001

ADMET: Metabolism

CYP1A2-inhibitor:   0.82 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.113
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.998
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.002
?
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):  9.865 Half-life (T1/2):  2.101

ADMET: Toxicity

hERG Blockers:  0.043 hERG Blockers (10um):  0.686
Human Hepatotoxicity (H-HT):  0.404 Drug-induced Liver Injury (DILI):  0.7
AMES Toxicity:  0.736 Rat Oral Acute Toxicity:  0.288
Maximum Recommended Daily Dose:  0.76 Skin Sensitization:  0.999
Carcinogencity:  0.237 Eye Corrosion:  0.007
Eye Irritation:  0.985 Respiratory Toxicity:  0.658
Drug-induced Neurotoxicity:  0.002 Ototoxicity:  0.889
Hematotoxicity:  0.038 Drug-induced Nephrotoxicity:  0.039
Genotoxicity:  0.998 RPMI-8226 Immunitoxicity:  0.018
A549 Cytotoxicity:  0.972 Hek293 Cytotoxicity:  0.528
BCF:   0.809
?
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:   3.362
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.424
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.779
?
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
NPO30276 Ampelopsis grossedentata Species Vitaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12328 Ampelopsis japonica Species Vitaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9729 Hovenia dulcis Species Rhamnaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27803 Cercidiphyllum japonicum Species Cercidiphyllaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12624 Pinus sp. Species Pinaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9729 Hovenia dulcis Species Rhamnaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO24057 Galla chinensis n.a. n.a. n.a. n.a. n.a. n.a. Database[HerDing]
NPO31087 Pinus sp Species Pinaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO12328 Ampelopsis japonica Species Vitaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO5490 Rhododendron cinnabarinum Species Ericaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO27803 Cercidiphyllum japonicum Species Cercidiphyllaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO30276 Ampelopsis grossedentata Species Vitaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO9729 Hovenia dulcis Species Rhamnaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO5490 Rhododendron cinnabarinum Species Ericaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO24057 Galla chinensis n.a. n.a. n.a. n.a. n.a. n.a. Database[TCMID]
NPO27803 Cercidiphyllum japonicum Species Cercidiphyllaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO12624 Pinus sp. Species Pinaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO12328 Ampelopsis japonica Species Vitaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO29193 Nekemias grossedentata Species Vitaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO30276 Ampelopsis grossedentata Species Vitaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO12328 Ampelopsis japonica Species Vitaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO5490 Rhododendron cinnabarinum Species Ericaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO27803 Cercidiphyllum japonicum Species Cercidiphyllaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO9729 Hovenia dulcis Species Rhamnaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO9729 Hovenia dulcis Species Rhamnaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO29193 Nekemias grossedentata Species Vitaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12328 Ampelopsis japonica Species Vitaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27803 Cercidiphyllum japonicum Species Cercidiphyllaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9729 Hovenia dulcis Species Rhamnaceae 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 NPC19724 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
0.72 Intermediate Similarity NPC19721
0.6226 Remote Similarity NPC325028
0.6226 Remote Similarity NPC256346
0.6226 Remote Similarity NPC606550
0.5849 Remote Similarity NPC21835
0.5714 Remote Similarity NPC36835
0.5714 Remote Similarity NPC246162
0.5714 Remote Similarity NPC9743
0.5714 Remote Similarity NPC260491
0.5714 Remote Similarity NPC61506
0.5714 Remote Similarity NPC240476
0.5636 Remote Similarity NPC122828
0.5536 Remote Similarity NPC176869
0.5536 Remote Similarity NPC3779
0.5439 Remote Similarity NPC250922
0.5345 Remote Similarity NPC611035
0.5179 Remote Similarity NPC62290
0.5179 Remote Similarity NPC142731
0.5179 Remote Similarity NPC326506
0.5179 Remote Similarity NPC4152
0.5088 Remote Similarity NPC246328
0.5088 Remote Similarity NPC27532
0.5088 Remote Similarity NPC201837

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC19724 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