Natural Product: NPC481771

Natural Product IDNPC481771
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 MVHAAGZZSATGDD-SFHVURJKSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 52316406
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0000337] Flavans
          • [CHEMONTID:0003645] 2'-prenylated flavans

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 MVHAAGZZSATGDD-SFHVURJKSA-N
Standard InCHI InChI=1S/C20H22O4/c1-12(2)3-7-16-15(8-9-17(22)20(16)23)18-10-5-13-4-6-14(21)11-19(13)24-18/h3-4,6,8-9,11,18,21-23H,5,7,10H2,1-2H3/t18-/m0/s1
SMILES CC(=CCc1c(ccc(c1O)O)[C@@H]1CCc2ccc(cc2O1)O)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   326.15 Volume:   345.512
?
Van der Waals volume.
Dense:   0.944 LogP:   3.706
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.217
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.567
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   18.0
TPSA:   69.92
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   3.0 Rings:   3.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.578 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.234 Fsp3:   0.3
MCE-18:   58.154
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Accepted GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   1 PAINS Alert:   1
Colloidal aggregators:   0.904 Fluc inhibitor:   0.959
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.064
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.138
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.486 Promiscuous compounds:   0.127

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.93 MDCK Permeability:   -4.794
Pgp-inhibitor:   0.003 Pgp-substrate:   0.184
PAMPA:   0.059
?
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):   0.002
20% Bioavailability (F20%):   0.99 30% Bioavailability (F30%):   0.996
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.029 MRP1:   0.973
Plasma Protein Binding (PPB):   94.762% Volume Distribution (VD):   0.064
Fu: 7.051%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.966
OATP1B3 inhibitor:   0.873 BCRP inhibitor:   0.861
BSEP inhibitor:   0.572

ADMET: Metabolism

CYP1A2-inhibitor:   0.003 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.921 CYP2C19-substrate:   1.0
CYP2C9-inhibitor:   0.415 CYP2C9-substrate:   0.002
CYP2D6-inhibitor:   0.973 CYP2D6-substrate:   0.014
CYP3A4-inhibitor:   0.543 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   1.0
?
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):  12.591 Half-life (T1/2):  1.72

ADMET: Toxicity

hERG Blockers:  0.232 hERG Blockers (10um):  0.664
Human Hepatotoxicity (H-HT):  0.777 Drug-induced Liver Injury (DILI):  0.374
AMES Toxicity:  0.571 Rat Oral Acute Toxicity:  0.82
Maximum Recommended Daily Dose:  0.861 Skin Sensitization:  0.948
Carcinogencity:  0.305 Eye Corrosion:  0.001
Eye Irritation:  0.656 Respiratory Toxicity:  0.934
Drug-induced Neurotoxicity:  0.81 Ototoxicity:  0.534
Hematotoxicity:  0.088 Drug-induced Nephrotoxicity:  0.726
Genotoxicity:  0.959 RPMI-8226 Immunitoxicity:  0.06
A549 Cytotoxicity:  0.741 Hek293 Cytotoxicity:  0.758
BCF:   1.836
?
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:   4.685
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.906
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.409
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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
NPO8912 Daphne giraldii Species Thymelaeaceae Eukaryota n.a. n.a. n.a. PMID[27627130]
NPO8912 Daphne giraldii Species Thymelaeaceae Eukaryota n.a. n.a. n.a. PMID[28371676]
NPO8912 Daphne giraldii Species Thymelaeaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8912 Daphne giraldii Species Thymelaeaceae 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
NPT65 Cell line HepG2 Homo sapiens IC50 > 100000.0 nM PMID[28371676]
NPT81 Cell line A549 Homo sapiens IC50 > 100000.0 nM PMID[28371676]
NPT83 Cell line MCF7 Homo sapiens IC50 > 100000.0 nM PMID[28371676]
NPT20904 Cell line Hep 3B2 Homo sapiens IC50 = 62200.0 nM PMID[28371676]

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 NPC481771 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 NPC234952
1.0 High Similarity NPC481770
0.7759 Intermediate Similarity NPC32630
0.7719 Intermediate Similarity NPC265075
0.6557 Remote Similarity NPC473413
0.6333 Remote Similarity NPC197351
0.6269 Remote Similarity NPC481758
0.6269 Remote Similarity NPC481759
0.6269 Remote Similarity NPC481760
0.6269 Remote Similarity NPC481756
0.6154 Remote Similarity NPC50250
0.6 Remote Similarity NPC474397
0.6 Remote Similarity NPC233980
0.6 Remote Similarity NPC481772
0.6 Remote Similarity NPC197679
0.5775 Remote Similarity NPC481757
0.5714 Remote Similarity NPC481763
0.5636 Remote Similarity NPC93398
0.5636 Remote Similarity NPC258979
0.5636 Remote Similarity NPC8283
0.5625 Remote Similarity NPC481767
0.5625 Remote Similarity NPC481769
0.5625 Remote Similarity NPC481768
0.5455 Remote Similarity NPC15543
0.5441 Remote Similarity NPC473845
0.5294 Remote Similarity NPC481764
0.5294 Remote Similarity NPC481766
0.5294 Remote Similarity NPC481765
0.527 Remote Similarity NPC67396
0.5167 Remote Similarity NPC36016

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC481771 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