Natural Product: NPC483381

Natural Product IDNPC483381
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 AVYGDWFATMFGNJ-UJFCTZSZSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 56968179
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0001392] Lignans, neolignans and related compounds
      • [CHEMONTID:0001511] Lignan glycosides

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 AVYGDWFATMFGNJ-UJFCTZSZSA-N
Standard InCHI InChI=1S/C26H24O11/c1-31-17-6-12-13(7-18(17)32-2)24(37-26-23(29)22(28)15(27)9-34-26)14-8-33-25(30)21(14)20(12)11-3-4-16-19(5-11)36-10-35-16/h3-7,15,22-23,26-29H,8-10H2,1-2H3/t15-,22+,23-,26+/m1/s1
SMILES COc1cc2c(cc1OC)c(c1COC(=O)c1c2c1ccc2c(c1)OCO2)O[C@H]1[C@@H]([C@H]([C@@H](CO1)O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   512.13 Volume:   479.878
?
Van der Waals volume.
Dense:   1.067 LogP:   1.855
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.077
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.236
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   32.0
TPSA:   142.37
?
Topological Polar Surface Area.
 H-Bond Acceptor:   11.0
H-Bond Donor:   3.0 Rings:   6.0
Heavy Atoms:   11.0

MedChem Properties

QED Drug-Likeness Score:   0.43 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.0 Fsp3:   0.346
MCE-18:   115.6
?
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:   0
Colloidal aggregators:   0.812 Fluc inhibitor:   0.101
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.713
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.697
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.025 Promiscuous compounds:   0.424

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.632 MDCK Permeability:   -4.803
Pgp-inhibitor:   0.003 Pgp-substrate:   0.11
PAMPA:   0.936
?
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):   0.006
20% Bioavailability (F20%):   0.021 30% Bioavailability (F30%):   0.001
50% Bioavailability (F50%):   0.746

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.047 MRP1:   0.216
Plasma Protein Binding (PPB):   95.408% Volume Distribution (VD):   -0.294
Fu: 5.247%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.998
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.192
BSEP inhibitor:   0.99

ADMET: Metabolism

CYP1A2-inhibitor:   0.939 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.772 CYP2C19-substrate:   0.001
CYP2C9-inhibitor:   0.039 CYP2C9-substrate:   0.001
CYP2D6-inhibitor:   0.002 CYP2D6-substrate:   0.841
CYP3A4-inhibitor:   0.008 CYP3A4-substrate:   0.927
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.399
HLM stability:   0.052
?
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):  2.594 Half-life (T1/2):  3.156

ADMET: Toxicity

hERG Blockers:  0.095 hERG Blockers (10um):  0.42
Human Hepatotoxicity (H-HT):  0.944 Drug-induced Liver Injury (DILI):  0.99
AMES Toxicity:  0.93 Rat Oral Acute Toxicity:  0.123
Maximum Recommended Daily Dose:  0.681 Skin Sensitization:  1.0
Carcinogencity:  0.885 Eye Corrosion:  0.0
Eye Irritation:  0.022 Respiratory Toxicity:  0.031
Drug-induced Neurotoxicity:  0.304 Ototoxicity:  0.937
Hematotoxicity:  0.917 Drug-induced Nephrotoxicity:  0.991
Genotoxicity:  0.948 RPMI-8226 Immunitoxicity:  0.418
A549 Cytotoxicity:  0.5 Hek293 Cytotoxicity:  0.687
BCF:   1.105
?
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:   3.654
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.729
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.598
?
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
NPO5865 Justicia gendarussa Species Acanthaceae Eukaryota n.a. n.a. n.a. PMID[28613071]
NPO5865 Justicia gendarussa Species Acanthaceae 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
NPT393 Cell line HCT-116 Homo sapiens IC50 = 820.0 nM PMID[22119124]
NPT83 Cell line MCF7 Homo sapiens IC50 = 1550.0 nM PMID[22119124]
NPT91 Cell line KB Homo sapiens IC50 = 410.0 nM PMID[22119124]
NPT91 Cell line KB Homo sapiens IC50 = 1190.0 nM PMID[22119124]
NPT111 Cell line K562 Homo sapiens IC50 = 4402.0 nM PMID[22119124]
NPT111 Cell line K562 Homo sapiens IC50 = 58820.0 nM PMID[22119124]
NPT91 Cell line KB Homo sapiens Ratio IC50 = 2.9 n.a. PMID[22119124]
NPT111 Cell line K562 Homo sapiens Ratio IC50 = 13.4 n.a. PMID[22119124]
NPT116 Cell line HL-60 Homo sapiens Activity = 45.6 % PMID[22119124]
NPT116 Cell line HL-60 Homo sapiens Activity = 47.0 % PMID[22119124]
NPT116 Cell line HL-60 Homo sapiens Activity = 35.5 % PMID[22119124]
NPT116 Cell line HL-60 Homo sapiens Activity = 33.8 % PMID[22119124]
NPT116 Cell line HL-60 Homo sapiens Activity = 18.9 % PMID[22119124]
NPT116 Cell line HL-60 Homo sapiens Activity = 19.2 % PMID[22119124]
NPT139 Cell line HT-29 Homo sapiens IC50 = 1400.0 nM PMID[29656990]
NPT377 Cell line OVCAR-3 Homo sapiens IC50 = 690.0 nM PMID[29656990]
NPT24 Organism Human immunodeficiency virus 1 Human immunodeficiency virus 1 IC50 = 510.0 nM PMID[28613071]

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 NPC483381 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 NPC474075
0.7821 Intermediate Similarity NPC184624
0.7722 Intermediate Similarity NPC114550
0.7722 Intermediate Similarity NPC312006
0.7722 Intermediate Similarity NPC602979
0.7625 Intermediate Similarity NPC129930
0.7561 Intermediate Similarity NPC471922
0.7439 Intermediate Similarity NPC471921
0.7407 Intermediate Similarity NPC20114
0.7273 Intermediate Similarity NPC35266
0.7273 Intermediate Similarity NPC167045
0.7273 Intermediate Similarity NPC114120
0.7143 Intermediate Similarity NPC239113
0.7143 Intermediate Similarity NPC292712
0.7097 Intermediate Similarity NPC161609
0.7059 Intermediate Similarity NPC471920
0.6901 Remote Similarity NPC19600
0.6471 Remote Similarity NPC473531
0.6438 Remote Similarity NPC115123
0.6437 Remote Similarity NPC471923
0.6383 Remote Similarity NPC275690
0.6275 Remote Similarity NPC286301
0.6275 Remote Similarity NPC313063
0.5957 Remote Similarity NPC473697
0.5921 Remote Similarity NPC78944
0.5714 Remote Similarity NPC15212
0.5393 Remote Similarity NPC474442
0.525 Remote Similarity NPC22130
0.519 Remote Similarity NPC299820
0.5125 Remote Similarity NPC143328
0.5119 Remote Similarity NPC196771

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC483381 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