Natural Product: NPC112755

Natural Product IDNPC112755
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 1,3,5-Trihydroxy-8-[(2R,3S,4R,5R,6S)-3,4,5-Trihydroxy-6-(Hydroxymethyl)Oxan-2-Yl]Oxyxanthen-9-One
IUPAC Name 1,3,5-trihydroxy-8-[(2R,3S,4R,5R,6S)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyxanthen-9-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1886292
PubChem CID 44202883
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 MYWLBRTZOYHDOU-UROUGOOJSA-N
Standard InCHI InChI=1S/C19H18O11/c20-5-11-14(24)16(26)17(27)19(30-11)29-9-2-1-7(22)18-13(9)15(25)12-8(23)3-6(21)4-10(12)28-18/h1-4,11,14,16-17,19-24,26-27H,5H2/t11-,14-,16+,17-,19-/m0/s1
SMILES c1cc(c2c(=O)c3c(cc(cc3oc2c1O)O)O)O[C@@H]1[C@H]([C@@H]([C@H]([C@H](CO)O1)O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   422.08 Volume:   381.192
?
Van der Waals volume.
Dense:   1.107 LogP:   0.385
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.075
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.85
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   23.0
TPSA:   190.28
?
Topological Polar Surface Area.
 H-Bond Acceptor:   11.0
H-Bond Donor:   7.0 Rings:   4.0
Heavy Atoms:   11.0

MedChem Properties

QED Drug-Likeness Score:   0.263 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.032 Fsp3:   0.316
MCE-18:   88.4
?
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:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.63 Fluc inhibitor:   0.239
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.836
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.507
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.249 Promiscuous compounds:   0.635

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.474 MDCK Permeability:   -5.026
Pgp-inhibitor:   0.0 Pgp-substrate:   0.716
PAMPA:   0.993
?
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):   0.908
20% Bioavailability (F20%):   0.675 30% Bioavailability (F30%):   0.999
50% Bioavailability (F50%):   0.997

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.006 MRP1:   0.192
Plasma Protein Binding (PPB):   84.67% Volume Distribution (VD):   0.024
Fu: 15.189%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.961
OATP1B3 inhibitor:   0.991 BCRP inhibitor:   0.806
BSEP inhibitor:   0.014

ADMET: Metabolism

CYP1A2-inhibitor:   0.003 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.002
CYP2C9-inhibitor:   0.031 CYP2C9-substrate:   0.07
CYP2D6-inhibitor:   0.011 CYP2D6-substrate:   0.349
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.007
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.999
HLM stability:   0.722
?
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):  2.226 Half-life (T1/2):  2.928

ADMET: Toxicity

hERG Blockers:  0.009 hERG Blockers (10um):  0.15
Human Hepatotoxicity (H-HT):  0.506 Drug-induced Liver Injury (DILI):  0.954
AMES Toxicity:  0.839 Rat Oral Acute Toxicity:  0.143
Maximum Recommended Daily Dose:  0.119 Skin Sensitization:  0.96
Carcinogencity:  0.336 Eye Corrosion:  0.0
Eye Irritation:  0.913 Respiratory Toxicity:  0.075
Drug-induced Neurotoxicity:  0.001 Ototoxicity:  0.454
Hematotoxicity:  0.066 Drug-induced Nephrotoxicity:  0.182
Genotoxicity:  0.876 RPMI-8226 Immunitoxicity:  0.111
A549 Cytotoxicity:  0.34 Hek293 Cytotoxicity:  0.289
BCF:   0.45
?
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:   2.959
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.302
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.566
?
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
NPO19705 Gentianella campestris Species Gentianaceae Eukaryota n.a. n.a. n.a. DOI[10.1002/hlca.19750580731]
NPO28011 Swertia japonica Species Gentianaceae Eukaryota n.a. n.a. n.a. DOI[10.1007/BF02675902]
NPO28011 Swertia japonica Species Gentianaceae Eukaryota n.a. n.a. n.a. DOI[10.1055/s-2008-1074888]
NPO28011 Swertia japonica Species Gentianaceae Eukaryota n.a. n.a. n.a. DOI[10.1248/cpb.30.4088]
NPO26420 Swertia perennis Species Gentianaceae Eukaryota n.a. n.a. n.a. DOI[1002/hlca.19760590517]
NPO28011 Swertia japonica Species Gentianaceae Eukaryota n.a. n.a. n.a. PMID[10353265]
NPO2743 Swertia purpurascens Species Gentianaceae Eukaryota n.a. n.a. n.a. PMID[1133711]
NPO19705 Gentianella campestris Species Gentianaceae Eukaryota n.a. n.a. n.a. PMID[15490334]
NPO28011 Swertia japonica Species Gentianaceae Eukaryota n.a. n.a. n.a. PMID[26996316]
NPO2743 Swertia purpurascens Species Gentianaceae Eukaryota n.a. n.a. n.a. PMID[4527698]
NPO28011 Swertia japonica Species Gentianaceae Eukaryota n.a. n.a. n.a. PMID[5583807]
NPO26420 Swertia perennis Species Gentianaceae Eukaryota n.a. n.a. n.a. PMID[931752]
NPO19705 Gentianella campestris Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[Article]
NPO28011 Swertia japonica Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26420 Swertia perennis Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO31193 Gentiana campestris Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2743 Swertia purpurascens Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO22592 Swertia randainensis Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15414 Swertia swertiopsis Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO22592 Swertia randainensis Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO26420 Swertia perennis Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO2743 Swertia purpurascens Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO31193 Gentiana campestris Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO28011 Swertia japonica Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO28011 Swertia japonica Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO22592 Swertia randainensis Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO26420 Swertia perennis Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO19705 Gentianella campestris Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO15414 Swertia swertiopsis Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO23984 Metagentiana rhodantha Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO2743 Swertia purpurascens Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO28011 Swertia japonica Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO31193 Gentiana campestris Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO26420 Swertia perennis Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO28011 Swertia japonica Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO28011 Swertia japonica Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2743 Swertia purpurascens Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23984 Metagentiana rhodantha Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19705 Gentianella campestris Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26420 Swertia perennis 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
NPT199 Individual protein DNA polymerase kappa Homo sapiens Potency n.a. 79432.8 nM PubChem BioAssay data set
NPT154 Individual protein Mothers against decapentaplegic homolog 3 Homo sapiens Potency n.a. 112.2 nM PubChem BioAssay data set
NPT10 Individual protein Geminin Homo sapiens Potency n.a. 1158.2 nM PubChem BioAssay data set
NPT10 Individual protein Geminin Homo sapiens Potency n.a. 73.1 nM PubChem BioAssay data set
NPT8 Individual protein DNA polymerase iota Homo sapiens Potency n.a. 50118.7 nM PubChem BioAssay data set
NPT755 Individual protein Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 Homo sapiens Potency n.a. 56234.1 nM PubChem BioAssay data set

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 NPC112755 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 NPC170675
0.7805 Intermediate Similarity NPC179947
0.7568 Intermediate Similarity NPC22195
0.7568 Intermediate Similarity NPC21190
0.6374 Remote Similarity NPC473618
0.5921 Remote Similarity NPC78697
0.5802 Remote Similarity NPC77672
0.5802 Remote Similarity NPC133671
0.5802 Remote Similarity NPC135391
0.5802 Remote Similarity NPC78263
0.5802 Remote Similarity NPC250069
0.5802 Remote Similarity NPC143851
0.5732 Remote Similarity NPC145038
0.5732 Remote Similarity NPC56077
0.5732 Remote Similarity NPC281131
0.5732 Remote Similarity NPC64305
0.5732 Remote Similarity NPC253662
0.5732 Remote Similarity NPC179950
0.5732 Remote Similarity NPC88789
0.5732 Remote Similarity NPC491374
0.5647 Remote Similarity NPC197285
0.5647 Remote Similarity NPC601710
0.561 Remote Similarity NPC19388
0.561 Remote Similarity NPC240431
0.561 Remote Similarity NPC55786
0.561 Remote Similarity NPC95855
0.5595 Remote Similarity NPC472459
0.5595 Remote Similarity NPC21100
0.5556 Remote Similarity NPC127415
0.5542 Remote Similarity NPC156457
0.5529 Remote Similarity NPC191306
0.5529 Remote Similarity NPC60735
0.5529 Remote Similarity NPC26230
0.5517 Remote Similarity NPC203050
0.5517 Remote Similarity NPC225434
0.5488 Remote Similarity NPC471416
0.5465 Remote Similarity NPC120099
0.5465 Remote Similarity NPC609478
0.5432 Remote Similarity NPC34287
0.5412 Remote Similarity NPC325555
0.5412 Remote Similarity NPC226304
0.5412 Remote Similarity NPC138540
0.5402 Remote Similarity NPC88023
0.5402 Remote Similarity NPC309025
0.5238 Remote Similarity NPC83283
0.5176 Remote Similarity NPC609879
0.5172 Remote Similarity NPC481043
0.5125 Remote Similarity NPC94777
0.506 Remote Similarity NPC288084

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC112755 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