Natural Product: NPC470600

Natural Product IDNPC470600
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Isojacareubin
IUPAC Name 6,10,11-trihydroxy-3,3-dimethyl-1,2-dihydropyrano[2,3-c]xanthen-7-one
Synonyms Isojacareubin
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL2087608
PubChem CID 70697351
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
                • [CHEMONTID:0003521] Pyranoxanthones

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 NNWFEKLCJFLWGN-UHFFFAOYSA-N
Standard InCHI InChI=1S/C18H16O6/c1-18(2)6-5-8-12(24-18)7-11(20)13-14(21)9-3-4-10(19)15(22)17(9)23-16(8)13/h3-4,7,19-20,22H,5-6H2,1-2H3
SMILES Oc1ccc2c(c1O)oc1c(c2=O)c(O)cc2c1CCC(O2)(C)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   328.09 Volume:   319.945
?
Van der Waals volume.
Dense:   1.025 LogP:   2.222
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.018
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.334
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The logarithm of aqueous solubility value.
Rotatable Bonds:   0.0 Rigid Bonds:   22.0
TPSA:   100.13
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Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   3.0 Rings:   4.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.433 GASA:   1.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.911 Fsp3:   0.278
MCE-18:   56.522
?
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:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   1 PAINS Alert:   1
Colloidal aggregators:   0.636 Fluc inhibitor:   0.514
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.973
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.757
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.123 Promiscuous compounds:   0.218

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.917 MDCK Permeability:   -4.692
Pgp-inhibitor:   0.192 Pgp-substrate:   0.033
PAMPA:   0.152
?
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):   0.005
20% Bioavailability (F20%):   0.87 30% Bioavailability (F30%):   0.993
50% Bioavailability (F50%):   0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.349 MRP1:   0.982
Plasma Protein Binding (PPB):   96.505% Volume Distribution (VD):   -0.208
Fu: 3.164%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.996
OATP1B3 inhibitor:   0.918 BCRP inhibitor:   0.962
BSEP inhibitor:   0.988

ADMET: Metabolism

CYP1A2-inhibitor:   0.002 CYP1A2-substrate:   0.836
CYP2C19-inhibitor:   0.001 CYP2C19-substrate:   0.826
CYP2C9-inhibitor:   0.19 CYP2C9-substrate:   0.03
CYP2D6-inhibitor:   0.057 CYP2D6-substrate:   0.245
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.539
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.984
HLM stability:   0.955
?
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):  6.376 Half-life (T1/2):  1.394

ADMET: Toxicity

hERG Blockers:  0.055 hERG Blockers (10um):  0.448
Human Hepatotoxicity (H-HT):  0.535 Drug-induced Liver Injury (DILI):  0.925
AMES Toxicity:  0.735 Rat Oral Acute Toxicity:  0.598
Maximum Recommended Daily Dose:  0.607 Skin Sensitization:  0.863
Carcinogencity:  0.757 Eye Corrosion:  0.007
Eye Irritation:  0.923 Respiratory Toxicity:  0.656
Drug-induced Neurotoxicity:  0.01 Ototoxicity:  0.282
Hematotoxicity:  0.146 Drug-induced Nephrotoxicity:  0.071
Genotoxicity:  0.806 RPMI-8226 Immunitoxicity:  0.055
A549 Cytotoxicity:  0.307 Hek293 Cytotoxicity:  0.319
BCF:   1.694
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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:   4.381
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.07
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.4
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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
NPO32443 garcinia nujiangensis Species Clusiaceae Eukaryota leaves n.a. n.a. PMID[22871217]
NPO32443 garcinia nujiangensis Species Clusiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]

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
NPT196 Cell line AGS Homo sapiens IC50 = 2500.0 nM PMID[18831569]
NPT83 Cell line MCF7 Homo sapiens IC50 = 3800.0 nM PMID[18831569]
NPT82 Cell line MDA-MB-231 Homo sapiens IC50 = 5900.0 nM PMID[17958396]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 9500.0 nM PMID[22871217]

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 NPC470600 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
0.7231 Intermediate Similarity NPC256925
0.6232 Remote Similarity NPC275122
0.6029 Remote Similarity NPC472281
0.6029 Remote Similarity NPC219867
0.5833 Remote Similarity NPC52204
0.5493 Remote Similarity NPC609342
0.5429 Remote Similarity NPC608857
0.5395 Remote Similarity NPC103238
0.5342 Remote Similarity NPC117992

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC470600 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