Natural Product: NPC180594

Natural Product IDNPC180594
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 CGQNAFNBYGFLTH-MWKIHXOOSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 643642
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000264] Organic acids and derivatives
      • [CHEMONTID:0000265] Carboxylic acids and derivatives
        • [CHEMONTID:0001093] Carboxylic acid derivatives
          • [CHEMONTID:0001238] Carboxylic acid esters

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 CGQNAFNBYGFLTH-MWKIHXOOSA-N
Standard InCHI InChI=1S/C17H23BrCl2O3/c1-4-6-7-8-15-13(19)9-14(20)17(22-11(3)21)10-16(23-15)12(18)5-2/h1,6-7,12-17H,5,8-10H2,2-3H3/b7-6-/t12-,13+,14+,15+,16-,17+/m1/s1
SMILES C#C/C=CC[C@H]1[C@H](C[C@@H]([C@H](C[C@H]([C@@H](CC)Br)O1)OC(=O)C)Cl)Cl

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   424.02 Volume:   359.562
?
Van der Waals volume.
Dense:   1.179 LogP:   3.572
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.315
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.103
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   11.0
TPSA:   35.53
?
Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   0.0 Rings:   1.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.371 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   5.099 Fsp3:   0.706
MCE-18:   24.828
?
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:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.854 Fluc inhibitor:   0.002
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.007
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.0
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.68 Promiscuous compounds:   0.526

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.639 MDCK Permeability:   -4.647
Pgp-inhibitor:   0.95 Pgp-substrate:   0.004
PAMPA:   0.454
?
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):   0.0
20% Bioavailability (F20%):   0.005 30% Bioavailability (F30%):   0.008
50% Bioavailability (F50%):   0.498

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.203 MRP1:   0.092
Plasma Protein Binding (PPB):   98.668% Volume Distribution (VD):   0.082
Fu: 1.457%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.825
OATP1B3 inhibitor:   0.156 BCRP inhibitor:   0.013
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.038 CYP1A2-substrate:   0.027
CYP2C19-inhibitor:   0.554 CYP2C19-substrate:   0.097
CYP2C9-inhibitor:   0.003 CYP2C9-substrate:   0.009
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.586
CYP3A4-inhibitor:   0.712 CYP3A4-substrate:   0.982
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.997
HLM stability:   0.92
?
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):  4.308 Half-life (T1/2):  1.578

ADMET: Toxicity

hERG Blockers:  0.005 hERG Blockers (10um):  0.157
Human Hepatotoxicity (H-HT):  0.429 Drug-induced Liver Injury (DILI):  0.187
AMES Toxicity:  0.935 Rat Oral Acute Toxicity:  0.874
Maximum Recommended Daily Dose:  0.229 Skin Sensitization:  0.988
Carcinogencity:  0.513 Eye Corrosion:  0.612
Eye Irritation:  0.929 Respiratory Toxicity:  0.995
Drug-induced Neurotoxicity:  0.421 Ototoxicity:  0.784
Hematotoxicity:  0.671 Drug-induced Nephrotoxicity:  0.922
Genotoxicity:  0.172 RPMI-8226 Immunitoxicity:  0.192
A549 Cytotoxicity:  0.129 Hek293 Cytotoxicity:  0.113
BCF:   0.798
?
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:   3.531
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.126
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.638
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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
NPO15600 Trifolium pannonicum Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2329 Scutellaria glabra Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10341 Pseudogymnoascus pannorum Species Pseudeurotiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1054 Peucedanum graveolens Species Apiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13493 Mauremys reevesii Species Geoemydidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5527 Ligularia atroviolacea Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2491 Laurencia obtusa Species Rhodomelaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18938 Ladeania juncea Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1221 Juniperus serawschanica Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8821 Delphinium dictyocarpum Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO666 Cymbidium aloifolium Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8821 Delphinium dictyocarpum Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO8821 Delphinium dictyocarpum Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO2491 Laurencia obtusa Species Rhodomelaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO666 Cymbidium aloifolium Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1221 Juniperus serawschanica Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2329 Scutellaria glabra Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13493 Mauremys reevesii Species Geoemydidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15600 Trifolium pannonicum Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18938 Ladeania juncea Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1054 Peucedanum graveolens Species Apiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8821 Delphinium dictyocarpum Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2491 Laurencia obtusa Species Rhodomelaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10341 Pseudogymnoascus pannorum Species Pseudeurotiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5527 Ligularia atroviolacea Species Asteraceae 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 NPC180594 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
0.5682 Remote Similarity NPC52781
0.5435 Remote Similarity NPC477424
0.5227 Remote Similarity NPC271000
0.5227 Remote Similarity NPC473306

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC180594 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