Natural Product: NPC482705

Natural Product IDNPC482705
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 LAQLCZKPJGMFRM-XMMISQBUSA-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]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0000337] Flavans
          • [CHEMONTID:0001632] Flavanones
            • [CHEMONTID:0001362] Flavanonols

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 LAQLCZKPJGMFRM-XMMISQBUSA-N
Standard InCHI InChI=1S/C25H28O5/c1-14(2)5-7-16-13-17(8-11-20(16)26)24-23(29)22(28)19-10-12-21(27)18(25(19)30-24)9-6-15(3)4/h5-6,8,10-13,23-24,26-27,29H,7,9H2,1-4H3/t23?,24-/m1/s1
SMILES CC(=CCc1cc(ccc1O)[C@@H]1C(C(=O)c2ccc(c(CC=C(C)C)c2O1)O)O)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   408.19 Volume:   435.51
?
Van der Waals volume.
Dense:   0.937 LogP:   4.246
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.362
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.753
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   20.0
TPSA:   86.99
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   3.0 Rings:   3.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.619 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.753 Fsp3:   0.32
MCE-18:   65.545
?
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:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.847 Fluc inhibitor:   0.268
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.603
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.606
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.252 Promiscuous compounds:   0.01

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.981 MDCK Permeability:   -4.67
Pgp-inhibitor:   0.834 Pgp-substrate:   0.033
PAMPA:   0.759
?
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):   0.569
20% Bioavailability (F20%):   0.998 30% Bioavailability (F30%):   1.0
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.601
Plasma Protein Binding (PPB):   94.115% Volume Distribution (VD):   0.457
Fu: 5.966%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.988
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   1.0
BSEP inhibitor:   0.443

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   1.0
CYP2C9-inhibitor:   0.287 CYP2C9-substrate:   0.012
CYP2D6-inhibitor:   0.756 CYP2D6-substrate:   0.96
CYP3A4-inhibitor:   0.522 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):  6.11 Half-life (T1/2):  1.761

ADMET: Toxicity

hERG Blockers:  0.062 hERG Blockers (10um):  0.617
Human Hepatotoxicity (H-HT):  0.757 Drug-induced Liver Injury (DILI):  0.32
AMES Toxicity:  0.699 Rat Oral Acute Toxicity:  0.899
Maximum Recommended Daily Dose:  0.312 Skin Sensitization:  0.937
Carcinogencity:  0.251 Eye Corrosion:  0.0
Eye Irritation:  0.268 Respiratory Toxicity:  0.817
Drug-induced Neurotoxicity:  0.651 Ototoxicity:  0.841
Hematotoxicity:  0.215 Drug-induced Nephrotoxicity:  0.929
Genotoxicity:  0.956 RPMI-8226 Immunitoxicity:  0.081
A549 Cytotoxicity:  0.451 Hek293 Cytotoxicity:  0.718
BCF:   1.971
?
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:   5.139
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.7
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   6.099
?
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
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota n.a. n.a. n.a. DOI[10.1007/s40502-015-0143-x]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota n.a. n.a. n.a. DOI[10.1093/pcp/pcg054]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota n.a. n.a. n.a. DOI[10.1134/S1021443709050069]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota Leaves n.a. n.a. PMID[12713396]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota roots n.a. n.a. PMID[20022509]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[21866899]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[23325115]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota Roots n.a. n.a. PMID[23541646]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[28140583]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[39683057]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[7381508]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO29384 Glycyrrhiza glabra Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO29384 Glycyrrhiza glabra Species Fabaceae 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
NPT178 Individual protein Protein-tyrosine phosphatase 1B Homo sapiens Inhibition = 43.9 % PMID[28140583]
NPT152 Individual protein Nuclear factor erythroid 2-related factor 2 Homo sapiens FC = 1.7 n.a. PMID[28140583]
NPT741 Individual protein Tyrosinase Homo sapiens Inhibition = 0.8 % PMID[28140583]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT113 Cell line RAW264.7 Mus musculus Inhibition = 0.0 % PMID[28140583]
NPT65 Cell line HepG2 Homo sapiens Inhibition = 39.0 % PMID[28140583]
NPT81 Cell line A549 Homo sapiens Inhibition = 24.8 % PMID[28140583]
NPT83 Cell line MCF7 Homo sapiens Inhibition = 33.2 % PMID[28140583]
NPT660 Cell line SW480 Homo sapiens Inhibition = 25.2 % PMID[28140583]
NPT2 Others Unspecified n.a. Inhibition = 37.0 % PMID[28140583]

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 NPC482705 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 NPC243171
0.8276 Intermediate Similarity NPC293286
0.7966 Intermediate Similarity NPC278476
0.7419 Intermediate Similarity NPC138288
0.7167 Intermediate Similarity NPC171651
0.6866 Remote Similarity NPC57313
0.6774 Remote Similarity NPC35567
0.6721 Remote Similarity NPC150408
0.6349 Remote Similarity NPC262038
0.6349 Remote Similarity NPC319910
0.619 Remote Similarity NPC236766
0.5781 Remote Similarity NPC164980
0.5758 Remote Similarity NPC66515
0.5758 Remote Similarity NPC197252
0.5758 Remote Similarity NPC254412
0.5479 Remote Similarity NPC477958
0.5373 Remote Similarity NPC149026
0.5362 Remote Similarity NPC608140
0.5303 Remote Similarity NPC482704
0.5224 Remote Similarity NPC91560
0.5147 Remote Similarity NPC221432
0.5147 Remote Similarity NPC257097
0.5135 Remote Similarity NPC477957

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC482705 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