Natural Product: NPC124569

Natural Product IDNPC124569
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 CKZPJNJRYRLITF-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 85730248
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0002448] Benzenoids
      • [CHEMONTID:0000023] Naphthalenes
        • [CHEMONTID:0002044] Phenylnaphthalenes

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 CKZPJNJRYRLITF-UHFFFAOYSA-N
Standard InCHI InChI=1S/C21H16O3/c1-23-18-12-16-17(22)11-9-14-8-10-15(13-6-4-3-5-7-13)20(19(14)16)21(18)24-2/h3-12H,1-2H3
SMILES COc1cc2C(=O)C=Cc3ccc(c4ccccc4)c(c23)c1OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   316.11 Volume:   337.552
?
Van der Waals volume.
Dense:   0.936 LogP:   4.08
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.737
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.719
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   22.0
TPSA:   35.53
?
Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   0.0 Rings:   4.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.7 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.404 Fsp3:   0.095
MCE-18:   42.0
?
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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.995 Fluc inhibitor:   0.702
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.808
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.993
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.456 Promiscuous compounds:   0.259

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.567 MDCK Permeability:   -4.674
Pgp-inhibitor:   0.656 Pgp-substrate:   0.095
PAMPA:   0.291
?
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):   0.004
20% Bioavailability (F20%):   0.002 30% Bioavailability (F30%):   0.007
50% Bioavailability (F50%):   0.03

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.363 MRP1:   0.742
Plasma Protein Binding (PPB):   98.523% Volume Distribution (VD):   0.411
Fu: 0.969%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.303
OATP1B3 inhibitor:   0.958 BCRP inhibitor:   0.368
BSEP inhibitor:   0.999

ADMET: Metabolism

CYP1A2-inhibitor:   0.335 CYP1A2-substrate:   0.514
CYP2C19-inhibitor:   0.127 CYP2C19-substrate:   0.304
CYP2C9-inhibitor:   0.061 CYP2C9-substrate:   0.059
CYP2D6-inhibitor:   0.09 CYP2D6-substrate:   0.764
CYP3A4-inhibitor:   0.41 CYP3A4-substrate:   0.745
CYP2B6-substrate:   0.008 CYP2C8-inhibitor:   0.998
HLM stability:   0.964
?
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):  6.068 Half-life (T1/2):  1.289

ADMET: Toxicity

hERG Blockers:  0.383 hERG Blockers (10um):  0.659
Human Hepatotoxicity (H-HT):  0.767 Drug-induced Liver Injury (DILI):  0.914
AMES Toxicity:  0.78 Rat Oral Acute Toxicity:  0.624
Maximum Recommended Daily Dose:  0.799 Skin Sensitization:  0.539
Carcinogencity:  0.875 Eye Corrosion:  0.004
Eye Irritation:  0.889 Respiratory Toxicity:  0.911
Drug-induced Neurotoxicity:  0.935 Ototoxicity:  0.525
Hematotoxicity:  0.79 Drug-induced Nephrotoxicity:  0.716
Genotoxicity:  0.742 RPMI-8226 Immunitoxicity:  0.153
A549 Cytotoxicity:  0.489 Hek293 Cytotoxicity:  0.727
BCF:   1.794
?
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:   4.6
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.056
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.661
?
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
NPO22441 Senna spectabilis Species Fabaceae Eukaryota flowers n.a. n.a. PMID[30413343]
NPO23044 Aesculus hippocastanum Species Sapindaceae Eukaryota n.a. n.a. n.a. PMID[3783160]
NPO18427 Axinella agnata Species Axinellidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23044 Aesculus hippocastanum Species Sapindaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10064 Diospyros canaliculata Species Ebenaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO22441 Senna spectabilis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10654 Lindera obtusiloba Species Lauraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16782 Andrographis viscosula Species Acanthaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5869 Anthocercis albicans Species Solanaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19091 Bacterium from n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO16548 Chenopodium formosanum Species Chenopodiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10984 Euclea crispa Species Ebenaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17900 Iotrochota birotulata Species Iotrochotidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11360 Tiliacora racemosa Species Menispermaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3096 Verbascum laxum Species Scrophulariaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10654 Lindera obtusiloba Species Lauraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO23044 Aesculus hippocastanum Species Sapindaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO23044 Aesculus hippocastanum Species Sapindaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO16782 Andrographis viscosula Species Acanthaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO10654 Lindera obtusiloba Species Lauraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO23044 Aesculus hippocastanum Species Sapindaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO10654 Lindera obtusiloba Species Lauraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO10654 Lindera obtusiloba Species Lauraceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO3096 Verbascum laxum Species Scrophulariaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10064 Diospyros canaliculata Species Ebenaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18427 Axinella agnata Species Axinellidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11360 Tiliacora racemosa Species Menispermaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10984 Euclea crispa Species Ebenaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22441 Senna spectabilis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5869 Anthocercis albicans Species Solanaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10654 Lindera obtusiloba Species Lauraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16548 Chenopodium formosanum Species Chenopodiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16782 Andrographis viscosula Species Acanthaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23044 Aesculus hippocastanum Species Sapindaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19091 Bacterium from n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO17900 Iotrochota birotulata Species Iotrochotidae 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

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 NPC124569 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
0.5263 Remote Similarity NPC300983

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC124569 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