Natural Product: NPC482969

Natural Product IDNPC482969
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 VVVZLBPMRUOLHO-MDWZMJQESA-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:0002507] Homoisoflavonoids

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 VVVZLBPMRUOLHO-MDWZMJQESA-N
Standard InCHI InChI=1S/C19H18O4S/c1-21-14-9-16(22-2)18-17(10-14)23-11-13(19(18)20)8-12-4-6-15(24-3)7-5-12/h4-10H,11H2,1-3H3/b13-8+
SMILES COc1cc(c2c(c1)OC/C(=Cc1ccc(cc1)SC)/C2=O)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   342.09 Volume:   344.089
?
Van der Waals volume.
Dense:   0.994 LogP:   3.484
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.379
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.201
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The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   19.0
TPSA:   44.76
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   0.0 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:   2.47 Fsp3:   0.211
MCE-18:   35.478
?
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:   0 PAINS Alert:   0
Colloidal aggregators:   0.96 Fluc inhibitor:   0.997
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.668
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.778
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.315 Promiscuous compounds:   0.06

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.966 MDCK Permeability:   -4.781
Pgp-inhibitor:   0.965 Pgp-substrate:   0.001
PAMPA:   0.046
?
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):   0.066
20% Bioavailability (F20%):   0.053 30% Bioavailability (F30%):   0.111
50% Bioavailability (F50%):   0.25

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.002 MRP1:   0.112
Plasma Protein Binding (PPB):   94.503% Volume Distribution (VD):   0.288
Fu: 4.176%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.956
OATP1B3 inhibitor:   0.998 BCRP inhibitor:   0.6
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.998
CYP2C19-inhibitor:   0.865 CYP2C19-substrate:   0.662
CYP2C9-inhibitor:   0.829 CYP2C9-substrate:   0.791
CYP2D6-inhibitor:   0.929 CYP2D6-substrate:   0.813
CYP3A4-inhibitor:   0.008 CYP3A4-substrate:   0.836
CYP2B6-substrate:   0.734 CYP2C8-inhibitor:   1.0
HLM stability:   0.724
?
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):  7.697 Half-life (T1/2):  0.522

ADMET: Toxicity

hERG Blockers:  0.506 hERG Blockers (10um):  0.608
Human Hepatotoxicity (H-HT):  0.797 Drug-induced Liver Injury (DILI):  0.999
AMES Toxicity:  0.745 Rat Oral Acute Toxicity:  0.909
Maximum Recommended Daily Dose:  0.92 Skin Sensitization:  0.985
Carcinogencity:  0.966 Eye Corrosion:  0.0
Eye Irritation:  0.049 Respiratory Toxicity:  0.757
Drug-induced Neurotoxicity:  0.802 Ototoxicity:  0.695
Hematotoxicity:  0.846 Drug-induced Nephrotoxicity:  0.957
Genotoxicity:  0.938 RPMI-8226 Immunitoxicity:  0.685
A549 Cytotoxicity:  0.884 Hek293 Cytotoxicity:  0.96
BCF:   2.049
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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:   4.487
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.735
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   6.049
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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
NPO40241 Hyacinthaceae Species n.a. n.a. n.a. n.a. n.a. PMID[30951308]
NPO40241 Hyacinthaceae Species n.a. n.a. n.a. n.a. n.a. Database[COCONUT]

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
NPT5265 Cell line Y79 Homo sapiens GI50 = 2000.0 nM PMID[30951308]
NPT21798 Cell line ARPE-19 Homo sapiens GI50 = 48000.0 nM PMID[30951308]
NPT2 Others Unspecified n.a. GI50 = 2500.0 nM PMID[30951308]
NPT2 Others Unspecified n.a. GI50 > 100000.0 nM PMID[30951308]

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 NPC482969 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
0.8043 Intermediate Similarity NPC482957
0.7333 Intermediate Similarity NPC125269
0.6275 Remote Similarity NPC293201
0.6 Remote Similarity NPC482970
0.5849 Remote Similarity NPC280284
0.5849 Remote Similarity NPC188947
0.5741 Remote Similarity NPC91236
0.5741 Remote Similarity NPC99333
0.5536 Remote Similarity NPC482971
0.537 Remote Similarity NPC477231
0.5319 Remote Similarity NPC211120
0.5273 Remote Similarity NPC31363
0.5273 Remote Similarity NPC257648
0.5179 Remote Similarity NPC170892
0.5179 Remote Similarity NPC297157

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC482969 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