Natural Product: NPC312763

Natural Product IDNPC312763
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Schisantherin L
IUPAC Name n.a.
Synonyms Schisantherin L
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL465719
PubChem CID 44567624
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 JTLHKPZZCOQRTA-LYFNIGRZSA-N
Standard InCHI InChI=1S/C27H30O9/c1-7-12(2)27(29)36-22-14(4)13(3)21(28)15-8-17-23(34-10-32-17)25(30-5)19(15)20-16(22)9-18-24(26(20)31-6)35-11-33-18/h7-9,13-14,21-22,28H,10-11H2,1-6H3/b12-7-/t13-,14+,21+,22+/m1/s1
SMILES C/C=C(C(=O)O[C@H]1[C@@H](C)[C@@H](C)[C@H](O)c2c(c3c1cc1OCOc1c3OC)c(OC)c1c(c2)OCO1)/C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   498.19 Volume:   490.786
?
Van der Waals volume.
Dense:   1.015 LogP:   3.861
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.434
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.21
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   28.0
TPSA:   101.91
?
Topological Polar Surface Area.
 H-Bond Acceptor:   9.0
H-Bond Donor:   1.0 Rings:   5.0
Heavy Atoms:   9.0

MedChem Properties

QED Drug-Likeness Score:   0.475 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.399 Fsp3:   0.444
MCE-18:   102.538
?
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:   0.888 Fluc inhibitor:   0.004
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.426
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.462
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.078 Promiscuous compounds:   0.209

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.073 MDCK Permeability:   -4.77
Pgp-inhibitor:   0.243 Pgp-substrate:   0.035
PAMPA:   0.639
?
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%):   0.18 30% Bioavailability (F30%):   0.0
50% Bioavailability (F50%):   0.832

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.739 MRP1:   0.99
Plasma Protein Binding (PPB):   97.742% Volume Distribution (VD):   0.014
Fu: 2.824%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.852
OATP1B3 inhibitor:   0.883 BCRP inhibitor:   0.003
BSEP inhibitor:   0.998

ADMET: Metabolism

CYP1A2-inhibitor:   0.974 CYP1A2-substrate:   0.998
CYP2C19-inhibitor:   0.849 CYP2C19-substrate:   0.978
CYP2C9-inhibitor:   0.366 CYP2C9-substrate:   1.0
CYP2D6-inhibitor:   0.162 CYP2D6-substrate:   0.998
CYP3A4-inhibitor:   0.479 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.004 CYP2C8-inhibitor:   0.007
HLM stability:   0.917
?
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):  4.284 Half-life (T1/2):  1.271

ADMET: Toxicity

hERG Blockers:  0.148 hERG Blockers (10um):  0.425
Human Hepatotoxicity (H-HT):  0.619 Drug-induced Liver Injury (DILI):  0.949
AMES Toxicity:  0.899 Rat Oral Acute Toxicity:  0.62
Maximum Recommended Daily Dose:  0.939 Skin Sensitization:  0.819
Carcinogencity:  0.936 Eye Corrosion:  0.0
Eye Irritation:  0.206 Respiratory Toxicity:  0.783
Drug-induced Neurotoxicity:  0.655 Ototoxicity:  0.586
Hematotoxicity:  0.712 Drug-induced Nephrotoxicity:  0.926
Genotoxicity:  0.953 RPMI-8226 Immunitoxicity:  0.346
A549 Cytotoxicity:  0.495 Hek293 Cytotoxicity:  0.692
BCF:   1.272
?
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:   3.49
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.326
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.244
?
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
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]
NPO18146 Kadsura angustifolia Species Schisandraceae Eukaryota stems Honghe Prefecture of Yunnan Province, China 2005-Oct PMID[18278869]
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]
NPO18146 Kadsura angustifolia Species Schisandraceae Eukaryota n.a. n.a. n.a. PMID[21232955]
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]
NPO18146 Kadsura angustifolia 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]
NPO912 Kadsura coccinea Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO18146 Kadsura angustifolia Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO912 Kadsura coccinea Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
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 > 200000.0 nM PMID[18278869]
NPT24 Organism Human immunodeficiency virus 1 Human immunodeficiency virus 1 EC50 = 137970.0 nM PMID[18278869]
NPT2 Others Unspecified n.a. Ratio = 2.91 n.a. PMID[18278869]

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 NPC312763 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
0.9649 High Similarity NPC24562
0.8421 Intermediate Similarity NPC473989
0.8136 Intermediate Similarity NPC325720
0.8136 Intermediate Similarity NPC316676
0.7167 Intermediate Similarity NPC327352
0.7167 Intermediate Similarity NPC198129
0.7167 Intermediate Similarity NPC252281
0.6935 Remote Similarity NPC322426
0.6719 Remote Similarity NPC316989
0.6615 Remote Similarity NPC85141
0.6429 Remote Similarity NPC475868
0.6286 Remote Similarity NPC477885
0.6207 Remote Similarity NPC324962
0.6087 Remote Similarity NPC308739
0.6 Remote Similarity NPC326144
0.5811 Remote Similarity NPC476065
0.5781 Remote Similarity NPC318286
0.5775 Remote Similarity NPC198461
0.5694 Remote Similarity NPC473323
0.5692 Remote Similarity NPC475865
0.5625 Remote Similarity NPC327651
0.5616 Remote Similarity NPC126405
0.5616 Remote Similarity NPC53669
0.5616 Remote Similarity NPC77237
0.5616 Remote Similarity NPC297271
0.5616 Remote Similarity NPC16791
0.5616 Remote Similarity NPC217708
0.5606 Remote Similarity NPC321958
0.56 Remote Similarity NPC475592
0.5538 Remote Similarity NPC172171
0.5538 Remote Similarity NPC239254
0.5429 Remote Similarity NPC474054
0.5424 Remote Similarity NPC474295
0.5373 Remote Similarity NPC230538
0.5373 Remote Similarity NPC321696
0.5373 Remote Similarity NPC229172
0.5373 Remote Similarity NPC103637
0.5373 Remote Similarity NPC36531
0.5325 Remote Similarity NPC483406
0.527 Remote Similarity NPC477380
0.5246 Remote Similarity NPC216434
0.5246 Remote Similarity NPC103448
0.5246 Remote Similarity NPC606558
0.5217 Remote Similarity NPC76415
0.5217 Remote Similarity NPC325122
0.5217 Remote Similarity NPC218510
0.507 Remote Similarity NPC474393
0.507 Remote Similarity NPC474347

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC312763 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