Natural Product: NPC68381

Natural Product IDNPC68381
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 2',3'-Di-O-Acetylfrangulina
IUPAC Name [(2S,3R,4R,5S,6S)-3-acetyloxy-2-(4,5-dihydroxy-7-methyl-9,10-dioxoanthracen-2-yl)oxy-5-hydroxy-6-methyloxan-4-yl] acetate
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL464290
PubChem CID 25107460
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 KCNQHDPLSQKCFV-QXXCCVGTSA-N
Standard InCHI InChI=1S/C25H24O11/c1-9-5-14-18(16(28)6-9)22(32)19-15(21(14)31)7-13(8-17(19)29)36-25-24(35-12(4)27)23(34-11(3)26)20(30)10(2)33-25/h5-8,10,20,23-25,28-30H,1-4H3/t10-,20-,23+,24+,25-/m0/s1
SMILES Cc1cc2c(c(c1)O)C(=O)c1c(cc(cc1O)O[C@H]1[C@@H]([C@@H]([C@H]([C@H](C)O1)O)OC(=O)C)OC(=O)C)C2=O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   500.13 Volume:   477.058
?
Van der Waals volume.
Dense:   1.048 LogP:   2.958
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.823
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.08
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   26.0
TPSA:   165.89
?
Topological Polar Surface Area.
 H-Bond Acceptor:   11.0
H-Bond Donor:   3.0 Rings:   4.0
Heavy Atoms:   11.0

MedChem Properties

QED Drug-Likeness Score:   0.445 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.083 Fsp3:   0.36
MCE-18:   95.529
?
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:   0
Chelating Alert:   0 PAINS Alert:   1
Colloidal aggregators:   0.625 Fluc inhibitor:   0.155
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.402
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.841
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.206 Promiscuous compounds:   0.475

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.669 MDCK Permeability:   -4.988
Pgp-inhibitor:   0.445 Pgp-substrate:   0.776
PAMPA:   0.99
?
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):   0.211
20% Bioavailability (F20%):   0.097 30% Bioavailability (F30%):   0.982
50% Bioavailability (F50%):   0.995

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.962
Plasma Protein Binding (PPB):   94.75% Volume Distribution (VD):   0.393
Fu: 6.116%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.06
BSEP inhibitor:   0.09

ADMET: Metabolism

CYP1A2-inhibitor:   0.001 CYP1A2-substrate:   0.01
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.033
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.552
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.001
CYP3A4-inhibitor:   0.001 CYP3A4-substrate:   0.019
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.989
?
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):  2.603 Half-life (T1/2):  1.909

ADMET: Toxicity

hERG Blockers:  0.019 hERG Blockers (10um):  0.286
Human Hepatotoxicity (H-HT):  0.672 Drug-induced Liver Injury (DILI):  0.997
AMES Toxicity:  0.981 Rat Oral Acute Toxicity:  0.187
Maximum Recommended Daily Dose:  0.093 Skin Sensitization:  0.984
Carcinogencity:  0.345 Eye Corrosion:  0.0
Eye Irritation:  0.576 Respiratory Toxicity:  0.184
Drug-induced Neurotoxicity:  0.048 Ototoxicity:  0.797
Hematotoxicity:  0.866 Drug-induced Nephrotoxicity:  0.948
Genotoxicity:  0.976 RPMI-8226 Immunitoxicity:  0.428
A549 Cytotoxicity:  0.952 Hek293 Cytotoxicity:  0.361
BCF:   0.932
?
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:   3.65
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.962
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.328
?
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
NPO32935 rhamnus nepalensis Species Rhamnaceae Eukaryota Leaves Pa Co, Mai Chau, Hoa Binh Province, 150 km west of Hanoi, Vietnam 1995-Nov PMID[11575949]

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
NPT1881 Nucleic acid Calf thymus DNA Bos taurus Kapp = 1.43 10'-7/M PMID[20561793]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT91 Cell line KB Homo sapiens IC50 = 1900.0 nM PMID[15974580]
NPT82 Cell line MDA-MB-231 Homo sapiens IC50 > 20000.0 nM PMID[1965654]
NPT116 Cell line HL-60 Homo sapiens IC50 = 3600.0 nM DrugMatrix in vitro pharmacology data
NPT91 Cell line KB Homo sapiens IC50 = 1100.0 nM DrugMatrix in vitro pharmacology data

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 NPC68381 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
0.7879 Intermediate Similarity NPC229817
0.7879 Intermediate Similarity NPC473686
0.7879 Intermediate Similarity NPC298778
0.7761 Intermediate Similarity NPC474345
0.7123 Intermediate Similarity NPC475662
0.7123 Intermediate Similarity NPC293227
0.7123 Intermediate Similarity NPC473717
0.6933 Remote Similarity NPC475220
0.6933 Remote Similarity NPC221140
0.6933 Remote Similarity NPC475352
0.6269 Remote Similarity NPC605264
0.6119 Remote Similarity NPC483778
0.5857 Remote Similarity NPC111536
0.5797 Remote Similarity NPC98776
0.55 Remote Similarity NPC312929
0.5082 Remote Similarity NPC56433

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC68381 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