Natural Product: NPC475856

Natural Product IDNPC475856
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Kadsulignan N
IUPAC Name n.a.
Synonyms Kadsulignan N
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL517461
PubChem CID 44567514
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000238] Tannins
        • [CHEMONTID:0001710] Hydrolyzable tannins

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 RRQAIPQPPCAEHD-SRRICDNISA-N
Standard InCHI InChI=1S/C24H30O7/c1-11-12(2)20-14-10-16(26-4)22(28-6)24(30-8)18(14)17-13(19(11)31-20)9-15(25-3)21(27-5)23(17)29-7/h9-12,19-20H,1-8H3/t11-,12+,19+,20-
SMILES COc1c2c(cc(c1OC)OC)[C@@H]1O[C@H](c3c2c(OC)c(c(c3)OC)OC)[C@@H]([C@@H]1C)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   430.2 Volume:   435.147
?
Van der Waals volume.
Dense:   0.989 LogP:   2.831
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.072
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.486
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   20.0
TPSA:   64.61
?
Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   0.0 Rings:   4.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.652 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.449 Fsp3:   0.5
MCE-18:   83.778
?
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:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.225 Fluc inhibitor:   0.314
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.282
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.252
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.315 Promiscuous compounds:   0.418

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.817 MDCK Permeability:   -4.668
Pgp-inhibitor:   0.319 Pgp-substrate:   0.069
PAMPA:   0.016
?
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):   0.001
20% Bioavailability (F20%):   0.071 30% Bioavailability (F30%):   0.007
50% Bioavailability (F50%):   0.742

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.858 MRP1:   0.998
Plasma Protein Binding (PPB):   89.791% Volume Distribution (VD):   0.015
Fu: 7.83%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.825
OATP1B3 inhibitor:   0.982 BCRP inhibitor:   0.406
BSEP inhibitor:   0.964

ADMET: Metabolism

CYP1A2-inhibitor:   0.927 CYP1A2-substrate:   0.279
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.673
CYP2C9-inhibitor:   0.001 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.424
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.997
HLM stability:   0.406
?
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):  7.721 Half-life (T1/2):  1.498

ADMET: Toxicity

hERG Blockers:  0.159 hERG Blockers (10um):  0.586
Human Hepatotoxicity (H-HT):  0.701 Drug-induced Liver Injury (DILI):  0.915
AMES Toxicity:  0.832 Rat Oral Acute Toxicity:  0.774
Maximum Recommended Daily Dose:  0.84 Skin Sensitization:  0.952
Carcinogencity:  0.776 Eye Corrosion:  0.003
Eye Irritation:  0.388 Respiratory Toxicity:  0.907
Drug-induced Neurotoxicity:  0.952 Ototoxicity:  0.524
Hematotoxicity:  0.886 Drug-induced Nephrotoxicity:  0.756
Genotoxicity:  0.552 RPMI-8226 Immunitoxicity:  0.414
A549 Cytotoxicity:  0.855 Hek293 Cytotoxicity:  0.662
BCF:   2.463
?
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:   3.842
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.864
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.259
?
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
NPO18146 Kadsura angustifolia Species Schisandraceae Eukaryota stems Honghe Prefecture of Yunnan Province, China 2005-Oct PMID[18278869]
NPO18146 Kadsura angustifolia Species Schisandraceae Eukaryota n.a. n.a. n.a. PMID[21232955]
NPO18146 Kadsura angustifolia Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18146 Kadsura angustifolia Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO18146 Kadsura angustifolia Species Schisandraceae 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
NPT1452 Cell line C8166 Homo sapiens CC50 = 381910.0 nM PMID[19586051]
NPT24 Organism Human immunodeficiency virus 1 Human immunodeficiency virus 1 EC50 = 43560.0 nM PMID[17125239]
NPT2 Others Unspecified n.a. Ratio = 8.77 n.a. PMID[16038534]

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 NPC475856 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
0.8158 Intermediate Similarity NPC216434
0.8158 Intermediate Similarity NPC103448
0.8158 Intermediate Similarity NPC606558
0.7632 Intermediate Similarity NPC474295
0.6364 Remote Similarity NPC326144
0.6222 Remote Similarity NPC141493
0.6111 Remote Similarity NPC9891
0.6111 Remote Similarity NPC88297
0.6111 Remote Similarity NPC186845
0.6087 Remote Similarity NPC865
0.5957 Remote Similarity NPC184928
0.5833 Remote Similarity NPC327651
0.5714 Remote Similarity NPC318286
0.549 Remote Similarity NPC321958
0.549 Remote Similarity NPC327352
0.549 Remote Similarity NPC198129
0.549 Remote Similarity NPC252281
0.549 Remote Similarity NPC321696
0.5283 Remote Similarity NPC322426
0.5283 Remote Similarity NPC76415
0.5283 Remote Similarity NPC218510
0.5283 Remote Similarity NPC208328
0.5238 Remote Similarity NPC31530
0.5116 Remote Similarity NPC50683
0.5116 Remote Similarity NPC72046
0.5116 Remote Similarity NPC261812
0.5116 Remote Similarity NPC112571
0.5116 Remote Similarity NPC65183
0.5116 Remote Similarity NPC285725
0.5091 Remote Similarity NPC316989

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC475856 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