Natural Product: NPC484344

Natural Product IDNPC484344
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 HQEMMMJDJZBZRJ-VIJSPRBVSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 102228232
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0001392] Lignans, neolignans and related compounds
      • [CHEMONTID:0003419] Cyclobutane lignans

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 HQEMMMJDJZBZRJ-VIJSPRBVSA-N
Standard InCHI InChI=1S/C30H24O6/c31-19-11-13-21(23(33)15-19)29(35)27-25(17-7-3-1-4-8-17)26(18-9-5-2-6-10-18)28(27)30(36)22-14-12-20(32)16-24(22)34/h1-16,25-28,31-34H/t25-,26-,27+,28+/m1/s1
SMILES c1ccc(cc1)[C@@H]1[C@@H](c2ccccc2)[C@@H]([C@H]1C(=O)c1ccc(cc1O)O)C(=O)c1ccc(cc1O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   480.16 Volume:   500.485
?
Van der Waals volume.
Dense:   0.959 LogP:   3.966
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.471
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.357
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   30.0
TPSA:   115.06
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   4.0 Rings:   5.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.275 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.547 Fsp3:   0.133
MCE-18:   93.824
?
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:   0
Colloidal aggregators:   0.979 Fluc inhibitor:   0.975
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.049
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.33
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.568 Promiscuous compounds:   0.179

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.108 MDCK Permeability:   -4.741
Pgp-inhibitor:   0.932 Pgp-substrate:   0.028
PAMPA:   0.034
?
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):   0.0
20% Bioavailability (F20%):   0.008 30% Bioavailability (F30%):   0.901
50% Bioavailability (F50%):   0.991

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.208 MRP1:   0.832
Plasma Protein Binding (PPB):   96.512% Volume Distribution (VD):   0.127
Fu: 4.914%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.359
BSEP inhibitor:   0.66

ADMET: Metabolism

CYP1A2-inhibitor:   0.836 CYP1A2-substrate:   0.845
CYP2C19-inhibitor:   0.002 CYP2C19-substrate:   0.981
CYP2C9-inhibitor:   0.003 CYP2C9-substrate:   0.946
CYP2D6-inhibitor:   0.06 CYP2D6-substrate:   0.758
CYP3A4-inhibitor:   0.853 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.995
HLM stability:   0.441
?
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):  0.959 Half-life (T1/2):  2.191

ADMET: Toxicity

hERG Blockers:  0.195 hERG Blockers (10um):  0.744
Human Hepatotoxicity (H-HT):  0.584 Drug-induced Liver Injury (DILI):  0.367
AMES Toxicity:  0.344 Rat Oral Acute Toxicity:  0.257
Maximum Recommended Daily Dose:  0.828 Skin Sensitization:  0.867
Carcinogencity:  0.214 Eye Corrosion:  0.014
Eye Irritation:  0.99 Respiratory Toxicity:  0.914
Drug-induced Neurotoxicity:  0.393 Ototoxicity:  0.136
Hematotoxicity:  0.016 Drug-induced Nephrotoxicity:  0.219
Genotoxicity:  0.991 RPMI-8226 Immunitoxicity:  0.053
A549 Cytotoxicity:  0.607 Hek293 Cytotoxicity:  0.976
BCF:   1.277
?
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:   4.865
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.408
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.208
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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
NPO40901 Oxytropis chiliophylla Species n.a. n.a. n.a. n.a. n.a. PMID[29400468]

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
NPT306 Cell line PC-3 Homo sapiens IC50 = 3800.0 nM PMID[29400468]
NPT306 Cell line PC-3 Homo sapiens Activity = 96.3 % PMID[29400468]
NPT306 Cell line PC-3 Homo sapiens Activity = 41.2 % PMID[29400468]

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 NPC484344 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 NPC484341
1.0 High Similarity NPC484342
1.0 High Similarity NPC484343
1.0 High Similarity NPC202856
0.7436 Intermediate Similarity NPC262435
0.7436 Intermediate Similarity NPC305858
0.7436 Intermediate Similarity NPC484340
0.5962 Remote Similarity NPC484345
0.5962 Remote Similarity NPC484346
0.5405 Remote Similarity NPC161617
0.5405 Remote Similarity NPC600232

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC484344 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