Natural Product: NPC481770

Natural Product IDNPC481770
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 MVHAAGZZSATGDD-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 51136520
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-UHFFFAOYSA-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
SMILES CC(=CCc1c(ccc(c1O)O)C1CCc2ccc(cc2O1)O)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   326.15 Volume:   345.512
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Van der Waals volume.
Dense:   0.944 LogP:   3.946
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.384
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.459
?
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
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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:   0.804 Fluc inhibitor:   0.601
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.178
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.282
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.425 Promiscuous compounds:   0.059

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.93 MDCK Permeability:   -4.763
Pgp-inhibitor:   0.009 Pgp-substrate:   0.035
PAMPA:   0.074
?
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%):   0.986 30% Bioavailability (F30%):   0.994
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.103 MRP1:   0.954
Plasma Protein Binding (PPB):   95.229% Volume Distribution (VD):   0.078
Fu: 6.794%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.988
OATP1B3 inhibitor:   0.989 BCRP inhibitor:   0.945
BSEP inhibitor:   0.701

ADMET: Metabolism

CYP1A2-inhibitor:   0.009 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.953 CYP2C19-substrate:   0.994
CYP2C9-inhibitor:   0.583 CYP2C9-substrate:   0.002
CYP2D6-inhibitor:   0.988 CYP2D6-substrate:   0.039
CYP3A4-inhibitor:   0.025 CYP3A4-substrate:   0.999
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.999
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):  11.471 Half-life (T1/2):  1.77

ADMET: Toxicity

hERG Blockers:  0.248 hERG Blockers (10um):  0.735
Human Hepatotoxicity (H-HT):  0.663 Drug-induced Liver Injury (DILI):  0.088
AMES Toxicity:  0.548 Rat Oral Acute Toxicity:  0.761
Maximum Recommended Daily Dose:  0.732 Skin Sensitization:  0.893
Carcinogencity:  0.426 Eye Corrosion:  0.0
Eye Irritation:  0.536 Respiratory Toxicity:  0.901
Drug-induced Neurotoxicity:  0.436 Ototoxicity:  0.544
Hematotoxicity:  0.111 Drug-induced Nephrotoxicity:  0.459
Genotoxicity:  0.871 RPMI-8226 Immunitoxicity:  0.043
A549 Cytotoxicity:  0.535 Hek293 Cytotoxicity:  0.784
BCF:   1.821
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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:   4.702
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.893
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.413
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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 = 81200.0 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 NPC481770 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 NPC481771
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 NPC481770 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