Natural Product: NPC103448

Natural Product IDNPC103448
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Neokadsuranin
IUPAC Name n.a.
Synonyms Neokadsuranin
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL485477
PubChem CID 44575997
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 RNIZTMIJCBCDBR-XJSVZPCESA-N
Standard InCHI InChI=1S/C23H26O7/c1-10-11(2)19-13-8-15-21(29-9-28-15)23(27-6)17(13)16-12(18(10)30-19)7-14(24-3)20(25-4)22(16)26-5/h7-8,10-11,18-19H,9H2,1-6H3/t10-,11+,18-,19+/m0/s1
SMILES COc1cc2[C@H]3O[C@H]([C@@H]([C@@H]3C)C)c3c(c2c(c1OC)OC)c(OC)c1c(c3)OCO1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   414.17 Volume:   409.295
?
Van der Waals volume.
Dense:   1.012 LogP:   2.884
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.961
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.325
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   24.0
TPSA:   64.61
?
Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   0.0 Rings:   5.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.729 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.687 Fsp3:   0.478
MCE-18:   95.529
?
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:   0.472 Fluc inhibitor:   0.111
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.519
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.251
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.233 Promiscuous compounds:   0.386

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.945 MDCK Permeability:   -4.744
Pgp-inhibitor:   0.068 Pgp-substrate:   0.028
PAMPA:   0.174
?
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):   0.0
20% Bioavailability (F20%):   0.011 30% Bioavailability (F30%):   0.0
50% Bioavailability (F50%):   0.698

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.71 MRP1:   0.959
Plasma Protein Binding (PPB):   87.016% Volume Distribution (VD):   0.058
Fu: 10.985%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.83
OATP1B3 inhibitor:   0.974 BCRP inhibitor:   0.064
BSEP inhibitor:   0.976

ADMET: Metabolism

CYP1A2-inhibitor:   0.997 CYP1A2-substrate:   0.616
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.842
CYP2C9-inhibitor:   0.049 CYP2C9-substrate:   0.563
CYP2D6-inhibitor:   0.229 CYP2D6-substrate:   0.982
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   0.996
CYP2B6-substrate:   0.005 CYP2C8-inhibitor:   0.057
HLM stability:   0.47
?
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):  5.805 Half-life (T1/2):  1.195

ADMET: Toxicity

hERG Blockers:  0.158 hERG Blockers (10um):  0.572
Human Hepatotoxicity (H-HT):  0.702 Drug-induced Liver Injury (DILI):  0.855
AMES Toxicity:  0.719 Rat Oral Acute Toxicity:  0.554
Maximum Recommended Daily Dose:  0.579 Skin Sensitization:  0.802
Carcinogencity:  0.848 Eye Corrosion:  0.003
Eye Irritation:  0.219 Respiratory Toxicity:  0.886
Drug-induced Neurotoxicity:  0.703 Ototoxicity:  0.644
Hematotoxicity:  0.856 Drug-induced Nephrotoxicity:  0.58
Genotoxicity:  0.146 RPMI-8226 Immunitoxicity:  0.293
A549 Cytotoxicity:  0.574 Hek293 Cytotoxicity:  0.466
BCF:   2.408
?
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:   4.237
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.051
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.197
?
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
NPO14102 Kadsura interior Species Schisandraceae Eukaryota n.a. n.a. n.a. PMID[12350139]
NPO912 Kadsura coccinea Species Schisandraceae Eukaryota n.a. n.a. n.a. PMID[18027905]
NPO912 Kadsura coccinea Species Schisandraceae Eukaryota n.a. n.a. n.a. PMID[18271558]
NPO912 Kadsura coccinea Species Schisandraceae Eukaryota roots n.a. n.a. PMID[18491866]
NPO912 Kadsura coccinea Species Schisandraceae Eukaryota n.a. n.a. n.a. PMID[18590312]
NPO912 Kadsura coccinea Species Schisandraceae Eukaryota n.a. n.a. n.a. PMID[24299567]
NPO912 Kadsura coccinea Species Schisandraceae Eukaryota n.a. n.a. n.a. PMID[26214125]
NPO912 Kadsura coccinea Species Schisandraceae Eukaryota Stems n.a. n.a. PMID[27704807]
NPO912 Kadsura coccinea Species Schisandraceae Eukaryota n.a. n.a. n.a. PMID[34684838]
NPO14102 Kadsura interior Species Schisandraceae Eukaryota n.a. stem n.a. PMID[8946749]
NPO25239 Kadsura peltigera Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO912 Kadsura coccinea Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14102 Kadsura interior Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25239 Kadsura peltigera Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO14102 Kadsura interior Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO25239 Kadsura peltigera Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO912 Kadsura coccinea Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO14102 Kadsura interior Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO25239 Kadsura peltigera Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO25239 Kadsura peltigera Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14102 Kadsura interior Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO912 Kadsura coccinea 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
NPT80 Cell line Raji Homo sapiens Activity = 70.0 % PMID[12350139]
NPT2 Others Unspecified n.a. Activity = 4.7 % PMID[12350139]
NPT2 Others Unspecified n.a. Activity = 51.6 % PMID[12350139]
NPT2 Others Unspecified n.a. Activity = 72.9 % PMID[12350139]
NPT2 Others Unspecified n.a. Activity = 92.6 % PMID[12350139]

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 NPC103448 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
1.0 High Similarity NPC216434
1.0 High Similarity NPC606558
0.9474 High Similarity NPC474295
0.8158 Intermediate Similarity NPC475856
0.7955 Intermediate Similarity NPC326144
0.7292 Intermediate Similarity NPC327651
0.7143 Intermediate Similarity NPC318286
0.6863 Remote Similarity NPC321958
0.6863 Remote Similarity NPC327352
0.6863 Remote Similarity NPC198129
0.6863 Remote Similarity NPC252281
0.6863 Remote Similarity NPC321696
0.6604 Remote Similarity NPC322426
0.6604 Remote Similarity NPC76415
0.6604 Remote Similarity NPC218510
0.6604 Remote Similarity NPC208328
0.6512 Remote Similarity NPC31530
0.6364 Remote Similarity NPC316989
0.6364 Remote Similarity NPC72046
0.6364 Remote Similarity NPC261812
0.6364 Remote Similarity NPC65183
0.6296 Remote Similarity NPC325122
0.614 Remote Similarity NPC319749
0.6071 Remote Similarity NPC325720
0.6071 Remote Similarity NPC316676
0.5957 Remote Similarity NPC145722
0.5957 Remote Similarity NPC256776
0.5957 Remote Similarity NPC185680
0.5714 Remote Similarity NPC324962
0.5714 Remote Similarity NPC473989
0.569 Remote Similarity NPC85141
0.56 Remote Similarity NPC136750
0.56 Remote Similarity NPC266848
0.5574 Remote Similarity NPC24562
0.5532 Remote Similarity NPC32189
0.5484 Remote Similarity NPC477380
0.5424 Remote Similarity NPC73467
0.541 Remote Similarity NPC471154
0.541 Remote Similarity NPC191352
0.541 Remote Similarity NPC308739
0.5397 Remote Similarity NPC477885
0.5385 Remote Similarity NPC141493
0.5333 Remote Similarity NPC252286
0.5306 Remote Similarity NPC475868
0.5303 Remote Similarity NPC63061
0.5303 Remote Similarity NPC475229
0.5283 Remote Similarity NPC865
0.5246 Remote Similarity NPC154971
0.5246 Remote Similarity NPC312763
0.5246 Remote Similarity NPC121661
0.5208 Remote Similarity NPC87295
0.5185 Remote Similarity NPC184928
0.5185 Remote Similarity NPC177868
0.5116 Remote Similarity NPC9891
0.5116 Remote Similarity NPC88297
0.5116 Remote Similarity NPC186845
0.5091 Remote Similarity NPC53722
0.5091 Remote Similarity NPC201404
0.5091 Remote Similarity NPC290714
0.5088 Remote Similarity NPC304821

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC103448 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