Natural Product: NPC111536

Natural Product IDNPC111536
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 1,8-Dihydroxy-3-Methyl-6-[(2S,3R,4S,5S,6R)-3,4,5-Trihydroxy-6-(Hydroxymethyl)Oxan-2-Yl]Oxyanthracene-9,10-Dione
IUPAC Name 1,8-dihydroxy-3-methyl-6-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyanthracene-9,10-dione
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL522084
PubChem CID 5317038
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0002448] Benzenoids
      • [CHEMONTID:0000018] Anthracenes
        • [CHEMONTID:0000151] Anthraquinones

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 UBVJENDWBOVRBS-JNHRPPPUSA-N
Standard InCHI InChI=1S/C21H20O10/c1-7-2-9-14(11(23)3-7)18(27)15-10(16(9)25)4-8(5-12(15)24)30-21-20(29)19(28)17(26)13(6-22)31-21/h2-5,13,17,19-24,26,28-29H,6H2,1H3/t13-,17-,19+,20-,21-/m1/s1
SMILES Cc1cc2c(c(c1)O)C(=O)c1c(cc(cc1O)O[C@H]1[C@@H]([C@H]([C@@H]([C@@H](CO)O1)O)O)O)C2=O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   432.11 Volume:   404.357
?
Van der Waals volume.
Dense:   1.069 LogP:   1.942
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.136
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.973
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   24.0
TPSA:   173.98
?
Topological Polar Surface Area.
 H-Bond Acceptor:   10.0
H-Bond Donor:   6.0 Rings:   4.0
Heavy Atoms:   10.0

MedChem Properties

QED Drug-Likeness Score:   0.312 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.905 Fsp3:   0.333
MCE-18:   90.643
?
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:   1
Colloidal aggregators:   0.552 Fluc inhibitor:   0.252
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.413
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.743
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.195 Promiscuous compounds:   0.434

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.145 MDCK Permeability:   -5.111
Pgp-inhibitor:   0.001 Pgp-substrate:   0.179
PAMPA:   0.999
?
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):   0.549
20% Bioavailability (F20%):   0.016 30% Bioavailability (F30%):   0.971
50% Bioavailability (F50%):   0.982

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.378
Plasma Protein Binding (PPB):   91.124% Volume Distribution (VD):   0.166
Fu: 9.391%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.041
BSEP inhibitor:   0.001

ADMET: Metabolism

CYP1A2-inhibitor:   0.011 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.001
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.004
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.992
HLM stability:   0.405
?
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):  2.496 Half-life (T1/2):  3.382

ADMET: Toxicity

hERG Blockers:  0.011 hERG Blockers (10um):  0.12
Human Hepatotoxicity (H-HT):  0.845 Drug-induced Liver Injury (DILI):  0.994
AMES Toxicity:  0.987 Rat Oral Acute Toxicity:  0.054
Maximum Recommended Daily Dose:  0.035 Skin Sensitization:  0.999
Carcinogencity:  0.518 Eye Corrosion:  0.0
Eye Irritation:  0.359 Respiratory Toxicity:  0.101
Drug-induced Neurotoxicity:  0.012 Ototoxicity:  0.946
Hematotoxicity:  0.839 Drug-induced Nephrotoxicity:  0.95
Genotoxicity:  0.962 RPMI-8226 Immunitoxicity:  0.434
A549 Cytotoxicity:  0.949 Hek293 Cytotoxicity:  0.421
BCF:   0.822
?
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:   3.443
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.844
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.076
?
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
NPO11391 Polygonum cuspidatum Species Polygonaceae Eukaryota n.a. n.a. n.a. PMID[11076555]
NPO11391 Polygonum cuspidatum Species Polygonaceae Eukaryota Roots n.a. n.a. PMID[11459643]
NPO11391 Polygonum cuspidatum Species Polygonaceae Eukaryota n.a. n.a. n.a. PMID[1517743]
NPO11391 Polygonum cuspidatum Species Polygonaceae Eukaryota n.a. n.a. n.a. PMID[8277318]
NPO7632 Rheum tanguticum Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11391 Polygonum cuspidatum Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28024 Rheum palmatum Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20881 Rheum officinale Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28024 Rheum palmatum Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO7632 Rheum tanguticum Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO11391 Polygonum cuspidatum Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO20881 Rheum officinale Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO11391 Polygonum cuspidatum Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO5990 Frangula alnus Species Rhamnaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO28024 Rheum palmatum Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO20881 Rheum officinale Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO7632 Rheum tanguticum Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO11391 Polygonum cuspidatum Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO20881 Rheum officinale Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO7632 Rheum tanguticum Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO28024 Rheum palmatum Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO11391 Polygonum cuspidatum Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO7632 Rheum tanguticum Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO20881 Rheum officinale Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO28024 Rheum palmatum Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO7632 Rheum tanguticum Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11391 Polygonum cuspidatum Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5990 Frangula alnus Species Rhamnaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28024 Rheum palmatum Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20881 Rheum officinale Species Polygonaceae 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
NPT13 Individual protein Tyrosine-protein kinase LCK Homo sapiens IC50 > 800.0 ug.mL-1 PMID[1479375]

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 NPC111536 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
0.875 High Similarity NPC483778
0.8276 Intermediate Similarity NPC605264
0.7333 Intermediate Similarity NPC222455
0.7273 Intermediate Similarity NPC76128
0.7231 Intermediate Similarity NPC271385
0.7231 Intermediate Similarity NPC30432
0.697 Remote Similarity NPC278329
0.6308 Remote Similarity NPC98776
0.6271 Remote Similarity NPC12308
0.6232 Remote Similarity NPC5029
0.6026 Remote Similarity NPC46958
0.6 Remote Similarity NPC146837
0.5857 Remote Similarity NPC68381
0.5806 Remote Similarity NPC214454
0.5789 Remote Similarity NPC312929
0.5694 Remote Similarity NPC101116
0.5571 Remote Similarity NPC604892
0.5538 Remote Similarity NPC23084
0.5479 Remote Similarity NPC212290
0.5479 Remote Similarity NPC604833
0.5429 Remote Similarity NPC8497
0.5429 Remote Similarity NPC610808
0.5345 Remote Similarity NPC56433
0.5342 Remote Similarity NPC605700
0.5342 Remote Similarity NPC606849
0.5263 Remote Similarity NPC178281
0.52 Remote Similarity NPC212099
0.52 Remote Similarity NPC199357
0.5167 Remote Similarity NPC142319
0.5139 Remote Similarity NPC600107
0.5077 Remote Similarity NPC154683
0.5072 Remote Similarity NPC599943
0.507 Remote Similarity NPC294166
0.507 Remote Similarity NPC115022
0.5068 Remote Similarity NPC210192
0.5068 Remote Similarity NPC189115

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC111536 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