Natural Product: NPC605079

Natural Product IDNPC605079
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 KTEXNACQROZXEV-QLIGOWBFSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL477923
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]

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 KTEXNACQROZXEV-QLIGOWBFSA-N
Standard InCHI InChI=1S/C15H20O3/c1-9-5-4-8-15(3)13(18-15)12-11(7-6-9)10(2)14(16)17-12/h5,11-13H,2,4,6-8H2,1,3H3/b9-5-/t11-,12-,13-,15+/m0/s1
SMILES C=C1C(=O)O[C@H]2[C@H]1CC/C(C)=CCC[C@@]1(C)O[C@@H]21

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   248.14 Volume:   260.788
?
Van der Waals volume.
Dense:   0.952 LogP:   2.724
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.782
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.14
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The logarithm of aqueous solubility value.
Rotatable Bonds:   0.0 Rigid Bonds:   18.0
TPSA:   38.83
?
Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   0.0 Rings:   3.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.286 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.723 Fsp3:   0.667
MCE-18:   47.52
?
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:   0 PAINS Alert:   0
Colloidal aggregators:   0.318 Fluc inhibitor:   0.273
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.009
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.085
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.774 Promiscuous compounds:   0.56

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.613 MDCK Permeability:   -4.746
Pgp-inhibitor:   0.861 Pgp-substrate:   0.009
PAMPA:   0.296
?
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):   0.209
20% Bioavailability (F20%):   0.61 30% Bioavailability (F30%):   0.979
50% Bioavailability (F50%):   0.989

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.054 MRP1:   0.793
Plasma Protein Binding (PPB):   91.202% Volume Distribution (VD):   0.102
Fu: 8.308%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   0.259
BSEP inhibitor:   0.995

ADMET: Metabolism

CYP1A2-inhibitor:   0.401 CYP1A2-substrate:   0.459
CYP2C19-inhibitor:   0.752 CYP2C19-substrate:   0.039
CYP2C9-inhibitor:   0.784 CYP2C9-substrate:   0.006
CYP2D6-inhibitor:   0.09 CYP2D6-substrate:   0.097
CYP3A4-inhibitor:   0.444 CYP3A4-substrate:   0.669
CYP2B6-substrate:   0.009 CYP2C8-inhibitor:   0.312
HLM stability:   0.644
?
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):  10.274 Half-life (T1/2):  1.26

ADMET: Toxicity

hERG Blockers:  0.019 hERG Blockers (10um):  0.145
Human Hepatotoxicity (H-HT):  0.784 Drug-induced Liver Injury (DILI):  0.794
AMES Toxicity:  0.471 Rat Oral Acute Toxicity:  0.257
Maximum Recommended Daily Dose:  0.377 Skin Sensitization:  0.999
Carcinogencity:  0.574 Eye Corrosion:  0.88
Eye Irritation:  0.962 Respiratory Toxicity:  0.095
Drug-induced Neurotoxicity:  0.252 Ototoxicity:  0.411
Hematotoxicity:  0.439 Drug-induced Nephrotoxicity:  0.685
Genotoxicity:  0.125 RPMI-8226 Immunitoxicity:  0.105
A549 Cytotoxicity:  0.194 Hek293 Cytotoxicity:  0.288
BCF:   1.953
?
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:   4.329
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.891
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.459
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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
NPO44838 Chrysanthemum parthenium Species Asteraceae Eukaryota 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
NPT50 Individual protein Tyrosyl-DNA phosphodiesterase 1 Homo sapiens Potency n.a. 2660.9 nM PubChem BioAssay data set
NPT50 Individual protein Tyrosyl-DNA phosphodiesterase 1 Homo sapiens Potency n.a. 2371.5 nM PubChem BioAssay data set
NPT692 Individual protein Histone deacetylase 6 Homo sapiens Inhibition = 9.8 % HDAC6 screening dataset using tau-based substrate in an enzymatic assay yields selective inhibitors and activators
NPT20556 Single protein Replicase polyprotein 1ab Severe acute respiratory syndrome coronavirus 2 Inhibition = 8.923 % Identification of inhibitors of SARS-Cov2 M-Pro enzymatic activity using a small molecule repurposing screen
NPT692 Individual protein Histone deacetylase 6 Homo sapiens Inhibition = 7.79 % HDAC6 screening dataset using tau-based substrate in an enzymatic assay yields selective inhibitors and activators

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT1535 Cell line U-87 MG Homo sapiens IC50 = 5750.0 nM PMID[32546298]
NPT393 Cell line HCT-116 Homo sapiens IC50 = 3130.0 nM PMID[32546298]
NPT76 Cell line C6 Rattus norvegicus IC50 = 3900.0 nM PMID[25102048]
NPT547 Cell line BGC-823 Homo sapiens IC50 = 15770.0 nM PMID[32546298]
NPT65 Cell line HepG2 Homo sapiens IC50 = 5710.0 nM PMID[32546298]
NPT71 Cell line HEK293 Homo sapiens IC50 = 8500.0 nM PMID[19269818]
NPT1970 Cell line THP-1 Homo sapiens Activity n.a. n.a. n.a. PMID[19269818]
NPT71 Cell line HEK293 Homo sapiens Activity n.a. n.a. n.a. PMID[19269818]
NPT83 Cell line MCF7 Homo sapiens IC50 = 5900.0 nM PMID[25102048]
NPT20555 Organism SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 Inhibition = -1.59 % Identification of inhibitors of SARS-CoV-2 in-vitro cellular toxicity in human (Caco-2) cells using a large scale drug repurposing collection
NPT28438 Unchecked Unchecked n.a. IC50 = 7400.0 nM PMID[19269818]
NPT20555 Organism SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 Inhibition = -0.32 % Cytopathic SARS-Cov2 screening on VERO-E6 cells in a large repurposing effort
NPT29074 Cell line PC-9 Homo sapiens IC50 = 6610.0 nM PMID[32546298]
NPT28438 Unchecked Unchecked n.a. Potency n.a. 14125.4 nM PubChem BioAssay data set
NPT28438 Unchecked Unchecked n.a. Potency n.a. 7943.3 nM PubChem BioAssay data set
NPT28438 Unchecked Unchecked n.a. Potency n.a. 35481.3 nM PubChem BioAssay data set
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 1200.0 nM PMID[25102048]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 7700.0 nM PMID[25102048]

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 NPC605079 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
1.0 High Similarity NPC38468
1.0 High Similarity NPC192678
1.0 High Similarity NPC319795
1.0 High Similarity NPC50362
1.0 High Similarity NPC488056
0.7708 Intermediate Similarity NPC608845
0.6939 Remote Similarity NPC49342
0.6939 Remote Similarity NPC251385
0.6346 Remote Similarity NPC303942
0.6346 Remote Similarity NPC57405
0.6327 Remote Similarity NPC207188
0.6296 Remote Similarity NPC605339
0.6154 Remote Similarity NPC151770
0.6 Remote Similarity NPC471147
0.5965 Remote Similarity NPC482125
0.5965 Remote Similarity NPC482124
0.5926 Remote Similarity NPC484396
0.5789 Remote Similarity NPC475659
0.569 Remote Similarity NPC487572
0.569 Remote Similarity NPC473859
0.5517 Remote Similarity NPC231889
0.551 Remote Similarity NPC58956
0.551 Remote Similarity NPC163003
0.551 Remote Similarity NPC295633
0.551 Remote Similarity NPC269206
0.5424 Remote Similarity NPC483718
0.5357 Remote Similarity NPC272814
0.5263 Remote Similarity NPC481994
0.5254 Remote Similarity NPC329857
0.5254 Remote Similarity NPC469718
0.5246 Remote Similarity NPC288876
0.5185 Remote Similarity NPC256273
0.5179 Remote Similarity NPC70251
0.5179 Remote Similarity NPC475881
0.5172 Remote Similarity NPC481908
0.5172 Remote Similarity NPC481801
0.5172 Remote Similarity NPC481993
0.5167 Remote Similarity NPC474035
0.5167 Remote Similarity NPC215988
0.5167 Remote Similarity NPC81386
0.5094 Remote Similarity NPC93213

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC605079 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
1.0 High Similarity NPD1733 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