Natural Product: NPC481772

Natural Product IDNPC481772
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 QSCBHDIGHKHWKC-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 70673796
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 QSCBHDIGHKHWKC-UHFFFAOYSA-N
Standard InCHI InChI=1S/C25H28O4/c1-15(2)5-9-19-20(13-17-11-12-25(3,4)29-24(17)23(19)27)21-10-7-16-6-8-18(26)14-22(16)28-21/h5-6,8,11-14,21,26-27H,7,9-10H2,1-4H3
SMILES CC(=CCc1c(cc2C=CC(C)(C)Oc2c1O)C1CCc2ccc(cc2O1)O)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   392.2 Volume:   420.799
?
Van der Waals volume.
Dense:   0.932 LogP:   5.598
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   4.111
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.383
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   23.0
TPSA:   58.92
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   2.0 Rings:   4.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.643 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.754 Fsp3:   0.36
MCE-18:   80.882
?
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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   1 PAINS Alert:   0
Colloidal aggregators:   0.954 Fluc inhibitor:   0.117
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.493
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.617
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.256 Promiscuous compounds:   0.045

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.968 MDCK Permeability:   -4.713
Pgp-inhibitor:   0.31 Pgp-substrate:   0.048
PAMPA:   0.072
?
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):   0.003
20% Bioavailability (F20%):   0.871 30% Bioavailability (F30%):   0.971
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.61 MRP1:   0.958
Plasma Protein Binding (PPB):   95.271% Volume Distribution (VD):   0.39
Fu: 4.707%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.989
OATP1B3 inhibitor:   0.952 BCRP inhibitor:   0.942
BSEP inhibitor:   0.991

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.998 CYP2C19-substrate:   1.0
CYP2C9-inhibitor:   0.099 CYP2C9-substrate:   0.002
CYP2D6-inhibitor:   0.008 CYP2D6-substrate:   0.245
CYP3A4-inhibitor:   0.113 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.313 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):  5.667 Half-life (T1/2):  1.468

ADMET: Toxicity

hERG Blockers:  0.294 hERG Blockers (10um):  0.726
Human Hepatotoxicity (H-HT):  0.634 Drug-induced Liver Injury (DILI):  0.158
AMES Toxicity:  0.49 Rat Oral Acute Toxicity:  0.852
Maximum Recommended Daily Dose:  0.829 Skin Sensitization:  0.682
Carcinogencity:  0.558 Eye Corrosion:  0.0
Eye Irritation:  0.175 Respiratory Toxicity:  0.948
Drug-induced Neurotoxicity:  0.558 Ototoxicity:  0.581
Hematotoxicity:  0.137 Drug-induced Nephrotoxicity:  0.499
Genotoxicity:  0.814 RPMI-8226 Immunitoxicity:  0.073
A549 Cytotoxicity:  0.411 Hek293 Cytotoxicity:  0.782
BCF:   2.197
?
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:   4.973
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.662
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   6.035
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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 = 92300.0 nM PMID[28371676]
NPT81 Cell line A549 Homo sapiens IC50 = 92500.0 nM PMID[28371676]
NPT83 Cell line MCF7 Homo sapiens IC50 > 100000.0 nM PMID[28371676]
NPT20904 Cell line Hep 3B2 Homo sapiens IC50 = 97800.0 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 NPC481772 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 NPC233980
1.0 High Similarity NPC197679
0.7042 Intermediate Similarity NPC481758
0.7042 Intermediate Similarity NPC481759
0.7042 Intermediate Similarity NPC481760
0.7042 Intermediate Similarity NPC481756
0.6757 Remote Similarity NPC474397
0.6494 Remote Similarity NPC43319
0.6377 Remote Similarity NPC265075
0.6338 Remote Similarity NPC481764
0.6338 Remote Similarity NPC481766
0.6338 Remote Similarity NPC481765
0.6 Remote Similarity NPC234952
0.6 Remote Similarity NPC481770
0.6 Remote Similarity NPC481771
0.5942 Remote Similarity NPC197351
0.5753 Remote Similarity NPC32630
0.5679 Remote Similarity NPC218226
0.5479 Remote Similarity NPC473413
0.5443 Remote Similarity NPC481763
0.5342 Remote Similarity NPC481767
0.5342 Remote Similarity NPC481769
0.5342 Remote Similarity NPC481768
0.5244 Remote Similarity NPC110303
0.5244 Remote Similarity NPC601247
0.5122 Remote Similarity NPC481757

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC481772 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