Natural Product: NPC50743

Natural Product IDNPC50743
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 UZQWHZRLSLEWHW-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 14034285
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0002585] O-methylated flavonoids
          • [CHEMONTID:0002591] 6-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 UZQWHZRLSLEWHW-UHFFFAOYSA-N
Standard InCHI InChI=1S/C16H14O7/c1-22-16-11(20)6-13-14(15(16)21)10(19)5-12(23-13)7-2-3-8(17)9(18)4-7/h2-4,6,12,17-18,20-21H,5H2,1H3
SMILES COc1c(cc2c(C(=O)CC(c3ccc(c(c3)O)O)O2)c1O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   318.07 Volume:   302.699
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Van der Waals volume.
Dense:   1.051 LogP:   1.872
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.089
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.716
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The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   18.0
TPSA:   116.45
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Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   4.0 Rings:   3.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.627 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.124 Fsp3:   0.188
MCE-18:   61.0
?
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:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   1
Chelating Alert:   1 PAINS Alert:   1
Colloidal aggregators:   0.717 Fluc inhibitor:   0.719
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.411
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.314
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.379 Promiscuous compounds:   0.241

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.225 MDCK Permeability:   -4.824
Pgp-inhibitor:   0.18 Pgp-substrate:   0.017
PAMPA:   0.218
?
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):   0.026
20% Bioavailability (F20%):   0.239 30% Bioavailability (F30%):   0.958
50% Bioavailability (F50%):   0.998

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.02 MRP1:   0.83
Plasma Protein Binding (PPB):   96.081% Volume Distribution (VD):   -0.45
Fu: 4.237%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.983
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   0.92
BSEP inhibitor:   0.147

ADMET: Metabolism

CYP1A2-inhibitor:   0.993 CYP1A2-substrate:   0.461
CYP2C19-inhibitor:   0.063 CYP2C19-substrate:   0.923
CYP2C9-inhibitor:   0.294 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.028 CYP2D6-substrate:   0.992
CYP3A4-inhibitor:   0.01 CYP3A4-substrate:   0.24
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.972
HLM stability:   0.992
?
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):  9.071 Half-life (T1/2):  1.472

ADMET: Toxicity

hERG Blockers:  0.076 hERG Blockers (10um):  0.635
Human Hepatotoxicity (H-HT):  0.551 Drug-induced Liver Injury (DILI):  0.581
AMES Toxicity:  0.661 Rat Oral Acute Toxicity:  0.515
Maximum Recommended Daily Dose:  0.535 Skin Sensitization:  0.965
Carcinogencity:  0.579 Eye Corrosion:  0.032
Eye Irritation:  0.985 Respiratory Toxicity:  0.576
Drug-induced Neurotoxicity:  0.087 Ototoxicity:  0.592
Hematotoxicity:  0.159 Drug-induced Nephrotoxicity:  0.182
Genotoxicity:  0.895 RPMI-8226 Immunitoxicity:  0.047
A549 Cytotoxicity:  0.792 Hek293 Cytotoxicity:  0.475
BCF:   0.979
?
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:   3.466
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.726
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.086
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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
NPO277 Caulis millettiae n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO2340 Caulis spatholobi n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO2340 Caulis spatholobi n.a. n.a. n.a. n.a. n.a. n.a. Database[HerDing]
NPO277 Caulis millettiae n.a. n.a. n.a. n.a. n.a. n.a. Database[TCMID]
NPO2340 Caulis spatholobi n.a. n.a. n.a. n.a. n.a. n.a. Database[TCMID]

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

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 NPC50743 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
0.8 Intermediate Similarity NPC606248
0.7547 Intermediate Similarity NPC474836
0.7451 Intermediate Similarity NPC255106
0.7451 Intermediate Similarity NPC235165
0.6667 Remote Similarity NPC321011
0.6667 Remote Similarity NPC294852
0.6667 Remote Similarity NPC188679
0.6182 Remote Similarity NPC610021
0.6 Remote Similarity NPC1612
0.6 Remote Similarity NPC183959
0.5965 Remote Similarity NPC474208
0.569 Remote Similarity NPC48208
0.5593 Remote Similarity NPC302950
0.5517 Remote Similarity NPC192083
0.5517 Remote Similarity NPC475267
0.5469 Remote Similarity NPC480158
0.5424 Remote Similarity NPC18727
0.541 Remote Similarity NPC236637
0.5357 Remote Similarity NPC103991
0.5345 Remote Similarity NPC300668
0.5345 Remote Similarity NPC480993
0.5345 Remote Similarity NPC329203
0.5345 Remote Similarity NPC324386
0.5345 Remote Similarity NPC222342
0.5263 Remote Similarity NPC32441
0.5263 Remote Similarity NPC79943
0.5254 Remote Similarity NPC486095
0.5143 Remote Similarity NPC213896
0.5088 Remote Similarity NPC225153
0.5088 Remote Similarity NPC479876
0.5085 Remote Similarity NPC274784
0.5085 Remote Similarity NPC20709
0.5077 Remote Similarity NPC610133

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC50743 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
0.5593 Remote Similarity NPD1934 Phase 0
0.5517 Remote Similarity NPD2393 Clinical (unspecified phase)
0.5263 Remote Similarity NPD1552 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