Natural Product: NPC485642

Natural Product IDNPC485642
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 VYESEQLQFXUROZ-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 2825024
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0002585] O-methylated flavonoids
          • [CHEMONTID:0002592] 7-O-methylated flavonoids

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 VYESEQLQFXUROZ-UHFFFAOYSA-N
Standard InCHI InChI=1S/C16H14O3/c1-18-12-7-8-13-14(17)10-15(19-16(13)9-12)11-5-3-2-4-6-11/h2-9,15H,10H2,1H3
SMILES COc1ccc2C(=O)CC(c3ccccc3)Oc2c1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   254.09 Volume:   267.538
?
Van der Waals volume.
Dense:   0.95 LogP:   3.408
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.461
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.244
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   18.0
TPSA:   35.53
?
Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   0.0 Rings:   3.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.824 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.382 Fsp3:   0.188
MCE-18:   48.158
?
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:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.543 Fluc inhibitor:   0.875
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.265
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.422
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.639 Promiscuous compounds:   0.078

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.661 MDCK Permeability:   -4.57
Pgp-inhibitor:   0.999 Pgp-substrate:   0.002
PAMPA:   0.028
?
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):   0.009
20% Bioavailability (F20%):   0.002 30% Bioavailability (F30%):   0.281
50% Bioavailability (F50%):   0.95

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.048 MRP1:   0.322
Plasma Protein Binding (PPB):   97.82% Volume Distribution (VD):   0.013
Fu: 1.209%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.986
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.994
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.989 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.941 CYP2C19-substrate:   0.973
CYP2C9-inhibitor:   0.914 CYP2C9-substrate:   0.061
CYP2D6-inhibitor:   0.826 CYP2D6-substrate:   0.969
CYP3A4-inhibitor:   0.009 CYP3A4-substrate:   0.025
CYP2B6-substrate:   0.889 CYP2C8-inhibitor:   0.763
HLM stability:   0.995
?
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):  4.037 Half-life (T1/2):  1.508

ADMET: Toxicity

hERG Blockers:  0.357 hERG Blockers (10um):  0.604
Human Hepatotoxicity (H-HT):  0.747 Drug-induced Liver Injury (DILI):  0.748
AMES Toxicity:  0.687 Rat Oral Acute Toxicity:  0.482
Maximum Recommended Daily Dose:  0.442 Skin Sensitization:  0.358
Carcinogencity:  0.76 Eye Corrosion:  0.031
Eye Irritation:  0.943 Respiratory Toxicity:  0.538
Drug-induced Neurotoxicity:  0.809 Ototoxicity:  0.389
Hematotoxicity:  0.5 Drug-induced Nephrotoxicity:  0.808
Genotoxicity:  0.26 RPMI-8226 Immunitoxicity:  0.075
A549 Cytotoxicity:  0.184 Hek293 Cytotoxicity:  0.407
BCF:   1.605
?
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:   4.048
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.446
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.889
?
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
NPO25653 Spatholobus suberectus Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[26690274]
NPO25653 Spatholobus suberectus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25653 Spatholobus suberectus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO25653 Spatholobus suberectus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO25653 Spatholobus suberectus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO25653 Spatholobus suberectus Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO25653 Spatholobus suberectus 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
NPT1443 Individual protein Pyruvate dehydrogenase kinase isoform 1 Homo sapiens Inhibition = 4.97 % PMID[28049590]
NPT582 Individual protein Monoamine oxidase B Homo sapiens IC50 = 1470.0 nM PMID[20045650]
NPT441 Individual protein Cytochrome P450 19A1 Homo sapiens IC50 = 8000.0 nM PMID[11909717]
NPT441 Individual protein Cytochrome P450 19A1 Homo sapiens IC50 = 8000.0 nM PMID[12270163]
NPT441 Individual protein Cytochrome P450 19A1 Homo sapiens IC50 = 8000.0 nM PMID[18042388]
NPT441 Individual protein Cytochrome P450 19A1 Homo sapiens Activity = 0.7 n.a. PMID[18042388]
NPT441 Individual protein Cytochrome P450 19A1 Homo sapiens IC50 = 80352.61 nM PMID[28622580]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT83 Cell line MCF7 Homo sapiens IC50 = 35700.0 nM PMID[11720850]
NPT71 Cell line HEK293 Homo sapiens FC = 1.1 n.a. PMID[19307119]
NPT2 Others Unspecified n.a. Ratio IC50 > 68.0 n.a. PMID[20045650]

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 NPC485642 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 NPC611561
0.6905 Remote Similarity NPC314329
0.6905 Remote Similarity NPC603208
0.6444 Remote Similarity NPC99854
0.6364 Remote Similarity NPC228184
0.6327 Remote Similarity NPC150648
0.5918 Remote Similarity NPC476480
0.5918 Remote Similarity NPC84585
0.5882 Remote Similarity NPC99597
0.5714 Remote Similarity NPC265871
0.5714 Remote Similarity NPC205093
0.56 Remote Similarity NPC22467
0.549 Remote Similarity NPC6407
0.549 Remote Similarity NPC545184
0.54 Remote Similarity NPC135616
0.5357 Remote Similarity NPC147145
0.5294 Remote Similarity NPC188243
0.5294 Remote Similarity NPC110228
0.5283 Remote Similarity NPC255106
0.5283 Remote Similarity NPC235165
0.5263 Remote Similarity NPC11566
0.5185 Remote Similarity NPC210084
0.5094 Remote Similarity NPC37392
0.5094 Remote Similarity NPC177354

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC485642 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
0.6905 Remote Similarity NPD1547 Clinical (unspecified phase)

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