Natural Product: NPC265380

Natural Product IDNPC265380
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 3-O-Demethylswertipunicoside
IUPAC Name 1,3,6,7-tetrahydroxy-4-(1,4,6,8-tetrahydroxy-9-oxoxanthen-2-yl)-2-[(2S,3R,4R,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]xanthen-9-one
Synonyms 3-O-Demethylswertipunicoside
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1214707
PubChem CID 10372399
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0000123] Benzopyrans
        • [CHEMONTID:0003410] 1-benzopyrans
          • [CHEMONTID:0002817] Dibenzopyrans
            • [CHEMONTID:0000200] Xanthenes
              • [CHEMONTID:0000204] Xanthones

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 SSBJLFDANWAXNG-KPTZWRFBSA-N
Standard InCHI InChI=1S/C32H24O17/c33-6-16-24(41)28(45)29(46)32(49-16)21-25(42)17(31-20(27(21)44)22(39)8-3-10(35)11(36)5-14(8)47-31)9-4-13(38)30-19(23(9)40)26(43)18-12(37)1-7(34)2-15(18)48-30/h1-5,16,24,28-29,32-38,40-42,44-46H,6H2/t16-,24-,28+,29-,32+/m1/s1
SMILES OC[C@H]1O[C@H]([C@@H]([C@H]([C@@H]1O)O)O)c1c(O)c(c2cc(O)c3c(c2O)c(=O)c2c(o3)cc(cc2O)O)c2c(c1O)c(=O)c1c(o2)cc(c(c1)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   680.1 Volume:   614.656
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Van der Waals volume.
Dense:   1.106 LogP:   0.568
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   0.625
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.526
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The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   40.0
TPSA:   312.41
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Topological Polar Surface Area.
 H-Bond Acceptor:   17.0
H-Bond Donor:   12.0 Rings:   7.0
Heavy Atoms:   17.0

MedChem Properties

QED Drug-Likeness Score:   0.071 GASA:   1.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.828 Fsp3:   0.188
MCE-18:   153.368
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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:   Accepted BMS Rule:   1
Chelating Alert:   1 PAINS Alert:   1
Colloidal aggregators:   0.701 Fluc inhibitor:   0.137
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.475
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.742
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.363 Promiscuous compounds:   0.869

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.511 MDCK Permeability:   -4.69
Pgp-inhibitor:   0.0 Pgp-substrate:   0.989
PAMPA:   1.0
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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):   0.13
20% Bioavailability (F20%):   0.24 30% Bioavailability (F30%):   1.0
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.892
Plasma Protein Binding (PPB):   87.541% Volume Distribution (VD):   -0.03
Fu: 11.009%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.023
OATP1B3 inhibitor:   0.773 BCRP inhibitor:   0.321
BSEP inhibitor:   0.499

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.883
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.334
?
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):  2.509 Half-life (T1/2):  6.0

ADMET: Toxicity

hERG Blockers:  0.007 hERG Blockers (10um):  0.133
Human Hepatotoxicity (H-HT):  0.596 Drug-induced Liver Injury (DILI):  0.999
AMES Toxicity:  0.916 Rat Oral Acute Toxicity:  0.199
Maximum Recommended Daily Dose:  0.789 Skin Sensitization:  0.996
Carcinogencity:  0.567 Eye Corrosion:  0.0
Eye Irritation:  0.787 Respiratory Toxicity:  0.059
Drug-induced Neurotoxicity:  0.0 Ototoxicity:  0.766
Hematotoxicity:  0.026 Drug-induced Nephrotoxicity:  0.008
Genotoxicity:  1.0 RPMI-8226 Immunitoxicity:  0.048
A549 Cytotoxicity:  0.92 Hek293 Cytotoxicity:  0.79
BCF:   0.598
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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:   3.385
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.445
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.946
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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
NPO14238 Swertia punicea Species Gentianaceae Eukaryota n.a. n.a. n.a. DOI[10.1002/cbdv.200490123]
NPO14238 Swertia punicea Species Gentianaceae Eukaryota n.a. whole plant n.a. DOI[10.1021/jo00025a032]
NPO14238 Swertia punicea Species Gentianaceae Eukaryota n.a. n.a. n.a. DOI[10.1021/np50072a022]
NPO14238 Swertia punicea Species Gentianaceae Eukaryota n.a. n.a. n.a. PMID[20677781]
NPO14238 Swertia punicea Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14238 Swertia punicea Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO14238 Swertia punicea Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO14238 Swertia punicea Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO14238 Swertia punicea Species Gentianaceae 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
NPT681 Cell line PC-12 Rattus norvegicus Activity = 157.8 % PMID[24809953]
NPT681 Cell line PC-12 Rattus norvegicus Activity = 95.5 % DrugMatrix in vivo data: Hematology

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 NPC265380 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
0.7935 Intermediate Similarity NPC185275
0.716 Intermediate Similarity NPC471789
0.6047 Remote Similarity NPC228383
0.6047 Remote Similarity NPC239644
0.5596 Remote Similarity NPC324742
0.5053 Remote Similarity NPC220912

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC265380 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