Natural Product: NPC483565

Natural Product IDNPC483565
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 MAODLBBKUGQHDU-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 122180875
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0002506] Isoflavonoids
        • [CHEMONTID:0002586] O-methylated isoflavonoids
          • [CHEMONTID:0002602] 7-O-methylated isoflavonoids
            • [CHEMONTID:0002689] 7-O-methylisoflavones

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 MAODLBBKUGQHDU-UHFFFAOYSA-N
Standard InCHI InChI=1S/C18H16O5/c1-9-15(20)14-16(21)13(11-4-6-12(19)7-5-11)8-23-18(14)10(2)17(9)22-3/h4-8,19-20H,1-3H3
SMILES Cc1c(c2c(=O)c(coc2c(C)c1OC)c1ccc(cc1)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   312.1 Volume:   317.074
?
Van der Waals volume.
Dense:   0.984 LogP:   2.563
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.127
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.528
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   18.0
TPSA:   79.9
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   2.0 Rings:   3.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.757 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.49 Fsp3:   0.167
MCE-18:   19.0
?
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:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.418 Fluc inhibitor:   0.836
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.763
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.619
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.345 Promiscuous compounds:   0.269

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.948 MDCK Permeability:   -4.762
Pgp-inhibitor:   0.067 Pgp-substrate:   0.253
PAMPA:   0.862
?
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):   0.015
20% Bioavailability (F20%):   0.217 30% Bioavailability (F30%):   0.173
50% Bioavailability (F50%):   0.847

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.222 MRP1:   0.862
Plasma Protein Binding (PPB):   96.967% Volume Distribution (VD):   -0.327
Fu: 2.645%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.634
OATP1B3 inhibitor:   0.595 BCRP inhibitor:   0.485
BSEP inhibitor:   0.751

ADMET: Metabolism

CYP1A2-inhibitor:   0.999 CYP1A2-substrate:   0.46
CYP2C19-inhibitor:   0.061 CYP2C19-substrate:   0.759
CYP2C9-inhibitor:   0.984 CYP2C9-substrate:   0.158
CYP2D6-inhibitor:   0.929 CYP2D6-substrate:   0.973
CYP3A4-inhibitor:   0.314 CYP3A4-substrate:   0.998
CYP2B6-substrate:   0.097 CYP2C8-inhibitor:   0.998
HLM stability:   0.005
?
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):  5.361 Half-life (T1/2):  0.915

ADMET: Toxicity

hERG Blockers:  0.096 hERG Blockers (10um):  0.532
Human Hepatotoxicity (H-HT):  0.572 Drug-induced Liver Injury (DILI):  0.607
AMES Toxicity:  0.463 Rat Oral Acute Toxicity:  0.58
Maximum Recommended Daily Dose:  0.734 Skin Sensitization:  0.578
Carcinogencity:  0.679 Eye Corrosion:  0.036
Eye Irritation:  0.971 Respiratory Toxicity:  0.71
Drug-induced Neurotoxicity:  0.386 Ototoxicity:  0.24
Hematotoxicity:  0.197 Drug-induced Nephrotoxicity:  0.226
Genotoxicity:  0.87 RPMI-8226 Immunitoxicity:  0.087
A549 Cytotoxicity:  0.247 Hek293 Cytotoxicity:  0.546
BCF:   1.268
?
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:   4.039
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.77
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.436
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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
NPO40535 Leiophyllum buxifolium Species Ericaceae Eukaryota n.a. n.a. n.a. PMID[26086179]

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
NPT82 Cell line MDA-MB-231 Homo sapiens IC50 = 7000.0 nM PMID[26086179]
NPT83 Cell line MCF7 Homo sapiens IC50 > 40000.0 nM PMID[26086179]
NPT27 Others Unspecified n.a. IC50 > 40000.0 nM PMID[26086179]

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
- Artemia salina LD50 = 20.2 uM PMID[26086179]

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 NPC483565 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
0.6607 Remote Similarity NPC295384
0.5932 Remote Similarity NPC131266
0.5932 Remote Similarity NPC269451
0.5833 Remote Similarity NPC216769
0.5833 Remote Similarity NPC303644
0.5821 Remote Similarity NPC6511
0.5781 Remote Similarity NPC204985
0.5652 Remote Similarity NPC237635
0.5574 Remote Similarity NPC159275
0.5522 Remote Similarity NPC219917
0.55 Remote Similarity NPC605229
0.5493 Remote Similarity NPC31627
0.5493 Remote Similarity NPC201731
0.5417 Remote Similarity NPC327269
0.541 Remote Similarity NPC7013
0.5405 Remote Similarity NPC476238
0.5373 Remote Similarity NPC24673
0.5333 Remote Similarity NPC470681
0.5323 Remote Similarity NPC181124
0.5323 Remote Similarity NPC162680
0.5323 Remote Similarity NPC100971
0.5238 Remote Similarity NPC283429
0.5231 Remote Similarity NPC285973
0.5217 Remote Similarity NPC168085
0.5211 Remote Similarity NPC117836
0.52 Remote Similarity NPC188403
0.5152 Remote Similarity NPC144118
0.5147 Remote Similarity NPC97716
0.5139 Remote Similarity NPC256406
0.5085 Remote Similarity NPC39426
0.5082 Remote Similarity NPC487222
0.5075 Remote Similarity NPC62518

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC483565 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
0.5085 Remote Similarity NPD1510 Phase 2

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