Natural Product: NPC482768

Natural Product IDNPC482768
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 FFAHIROHRBNAFE-IHZPVSPSSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]

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 FFAHIROHRBNAFE-IHZPVSPSSA-N
Standard InCHI InChI=1S/C26H26O7/c27-21-15-7-13-19(31-21)23(29)25(17-9-3-1-4-10-17)33-26(18-11-5-2-6-12-18)24(30)20-14-8-16-22(28)32-20/h1-12,15-16,19-20,23-26,29-30H,13-14H2/t19-,20-,23-,24-,25-,26+/m0/s1
SMILES c1ccc(cc1)[C@@H]([C@H]([C@@H]1CC=CC(=O)O1)O)O[C@H](c1ccccc1)[C@H]([C@@H]1CC=CC(=O)O1)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   450.17 Volume:   459.193
?
Van der Waals volume.
Dense:   0.98 LogP:   2.371
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.415
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.899
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   8.0 Rigid Bonds:   26.0
TPSA:   102.29
?
Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   2.0 Rings:   4.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.596 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.531 Fsp3:   0.308
MCE-18:   71.176
?
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:   0.836 Fluc inhibitor:   0.013
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.115
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.353
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.579 Promiscuous compounds:   0.361

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.172 MDCK Permeability:   -4.961
Pgp-inhibitor:   0.066 Pgp-substrate:   0.002
PAMPA:   0.974
?
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%):   0.0 30% Bioavailability (F30%):   0.032
50% Bioavailability (F50%):   0.058

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.564 MRP1:   0.527
Plasma Protein Binding (PPB):   90.456% Volume Distribution (VD):   -0.124
Fu: 11.925%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.729
OATP1B3 inhibitor:   0.965 BCRP inhibitor:   0.0
BSEP inhibitor:   0.632

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.001 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.013 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.075 CYP3A4-substrate:   0.01
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.232
HLM stability:   0.927
?
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):  4.554 Half-life (T1/2):  2.838

ADMET: Toxicity

hERG Blockers:  0.03 hERG Blockers (10um):  0.498
Human Hepatotoxicity (H-HT):  0.497 Drug-induced Liver Injury (DILI):  0.801
AMES Toxicity:  0.528 Rat Oral Acute Toxicity:  0.668
Maximum Recommended Daily Dose:  0.548 Skin Sensitization:  1.0
Carcinogencity:  0.171 Eye Corrosion:  0.955
Eye Irritation:  0.995 Respiratory Toxicity:  0.174
Drug-induced Neurotoxicity:  0.862 Ototoxicity:  0.395
Hematotoxicity:  0.353 Drug-induced Nephrotoxicity:  0.894
Genotoxicity:  0.92 RPMI-8226 Immunitoxicity:  0.073
A549 Cytotoxicity:  0.353 Hek293 Cytotoxicity:  0.223
BCF:   1.137
?
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:   3.924
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.176
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.835
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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
NPO40148 Goniothalamus lanceolatus Species Annonaceae Eukaryota n.a. n.a. n.a. PMID[31433181]

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
NPT81 Cell line A549 Homo sapiens IC50 = 7800.0 nM PMID[31433181]
NPT1307 Cell line Calu-1 Homo sapiens IC50 = 5400.0 nM PMID[31433181]
NPT2410 Cell line NCI-H1299 Homo sapiens IC50 = 7100.0 nM PMID[31433181]
NPT370 Cell line NCI-H23 Homo sapiens IC50 = 3200.0 nM PMID[31433181]
NPT171 Cell line MRC5 Homo sapiens IC50 > 100000.0 nM PMID[31433181]
NPT391 Cell line HCC 2998 Homo sapiens IC50 = 2900.0 nM PMID[31433181]
NPT492 Cell line Caco-2 Homo sapiens IC50 > 10000.0 nM PMID[31433181]
NPT2338 Cell line SW48 Homo sapiens IC50 = 4100.0 nM PMID[31433181]
NPT393 Cell line HCT-116 Homo sapiens IC50 = 5900.0 nM PMID[31433181]
NPT21740 Cell line CCD-841CoN Homo sapiens IC50 > 100000.0 nM PMID[31433181]

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 NPC482768 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
0.8537 High Similarity NPC474376
0.814 Intermediate Similarity NPC475203
0.7255 Intermediate Similarity NPC482770
0.6604 Remote Similarity NPC482769
0.5957 Remote Similarity NPC280616
0.5957 Remote Similarity NPC171831
0.5957 Remote Similarity NPC242913
0.5957 Remote Similarity NPC608953
0.5833 Remote Similarity NPC475465
0.5833 Remote Similarity NPC472314
0.551 Remote Similarity NPC277788
0.5098 Remote Similarity NPC172525

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC482768 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