Natural Product: NPC602206

Natural Product IDNPC602206
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 JZODKRWQWUWGCD-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL480626
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 JZODKRWQWUWGCD-UHFFFAOYSA-N
Standard InCHI InChI=1S/C14H22O2/c1-13(2,3)9-7-12(16)10(8-11(9)15)14(4,5)6/h7-8,15-16H,1-6H3
SMILES CC(C)(C)c1cc(O)c(C(C)(C)C)cc1O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   222.16 Volume:   251.815
?
Van der Waals volume.
Dense:   0.882 LogP:   3.621
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.369
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.867
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The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   6.0
TPSA:   40.46
?
Topological Polar Surface Area.
 H-Bond Acceptor:   2.0
H-Bond Donor:   2.0 Rings:   1.0
Heavy Atoms:   2.0

MedChem Properties

QED Drug-Likeness Score:   0.657 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.379 Fsp3:   0.571
MCE-18:   13.0
?
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:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.136 Fluc inhibitor:   0.048
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.007
?
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:   0.979 Promiscuous compounds:   0.124

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.938 MDCK Permeability:   -4.711
Pgp-inhibitor:   0.905 Pgp-substrate:   0.31
PAMPA:   0.257
?
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):   0.776
20% Bioavailability (F20%):   0.989 30% Bioavailability (F30%):   0.996
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.432
Plasma Protein Binding (PPB):   89.004% Volume Distribution (VD):   0.186
Fu: 10.004%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   0.994 BCRP inhibitor:   0.01
BSEP inhibitor:   0.972

ADMET: Metabolism

CYP1A2-inhibitor:   0.205 CYP1A2-substrate:   0.72
CYP2C19-inhibitor:   0.143 CYP2C19-substrate:   0.005
CYP2C9-inhibitor:   0.626 CYP2C9-substrate:   0.667
CYP2D6-inhibitor:   0.484 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.849 CYP3A4-substrate:   0.922
CYP2B6-substrate:   0.248 CYP2C8-inhibitor:   0.487
HLM stability:   0.335
?
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):  8.101 Half-life (T1/2):  0.802

ADMET: Toxicity

hERG Blockers:  0.107 hERG Blockers (10um):  0.819
Human Hepatotoxicity (H-HT):  0.218 Drug-induced Liver Injury (DILI):  0.116
AMES Toxicity:  0.075 Rat Oral Acute Toxicity:  0.43
Maximum Recommended Daily Dose:  0.681 Skin Sensitization:  0.677
Carcinogencity:  0.174 Eye Corrosion:  0.922
Eye Irritation:  0.997 Respiratory Toxicity:  0.815
Drug-induced Neurotoxicity:  0.493 Ototoxicity:  0.53
Hematotoxicity:  0.121 Drug-induced Nephrotoxicity:  0.2
Genotoxicity:  0.007 RPMI-8226 Immunitoxicity:  0.065
A549 Cytotoxicity:  0.848 Hek293 Cytotoxicity:  0.498
BCF:   2.472
?
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:   5.062
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.449
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.958
?
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
NPO44782 Streptomyces bacillaris strain RAM25C4 Genus Streptomycetaceae Bacteria 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
NPT198 Individual protein Vitamin D receptor Homo sapiens Potency n.a. 28183.8 nM PubChem BioAssay data set
NPT208 Individual protein Cytochrome P450 1A2 Homo sapiens AC50 = 10000.0 nM PubChem BioAssay data set
NPT212 Individual protein Cytochrome P450 2C9 Homo sapiens AC50 n.a. n.a. n.a. PubChem BioAssay data set
NPT110 Individual protein Cytochrome P450 2D6 Homo sapiens AC50 n.a. n.a. n.a. PubChem BioAssay data set
NPT213 Individual protein Cytochrome P450 2C19 Homo sapiens AC50 n.a. n.a. n.a. PubChem BioAssay data set
NPT150 Individual protein Anthrax lethal factor Bacillus anthracis Potency = 25118.9 nM PubChem BioAssay data set
NPT198 Individual protein Vitamin D receptor Homo sapiens Potency n.a. 50118.7 nM PubChem BioAssay data set
NPT109 Individual protein Cytochrome P450 3A4 Homo sapiens AC50 n.a. n.a. n.a. PubChem BioAssay data set
NPT50 Individual protein Tyrosyl-DNA phosphodiesterase 1 Homo sapiens Potency n.a. 10593.1 nM PubChem BioAssay data set
NPT55 Individual protein Putative fructose-1,6-bisphosphate aldolase Giardia intestinalis Potency = 4456.3 nM PubChem BioAssay data set
NPT50 Individual protein Tyrosyl-DNA phosphodiesterase 1 Homo sapiens Potency n.a. 11885.6 nM PubChem BioAssay data set
NPT21779 Single protein Sarcoplasmic/endoplasmic reticulum calcium ATPase 3 Homo sapiens IC50 = 2000.0 nM PMID[32030976]
NPT94 Individual protein Aldehyde dehydrogenase 1A1 Homo sapiens Potency = 39810.7 nM PubChem BioAssay data set
NPT4044 Individual protein Short transient receptor potential channel 4 Mus musculus EC50 n.a. 376.0 nM PubChem BioAssay data set
NPT444 Individual protein Ubiquitin carboxyl-terminal hydrolase 1 Homo sapiens Potency n.a. 44668.4 nM PubChem BioAssay data set
NPT692 Individual protein Histone deacetylase 6 Homo sapiens Inhibition = 10.66 % 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 = -25.81 % Identification of inhibitors of SARS-Cov2 M-Pro enzymatic activity using a small molecule repurposing screen
NPT5536 Individual protein Sarcoplasmic/endoplasmic reticulum calcium ATP-ase Oryctolagus cuniculus IC50 = 2000.0 nM PMID[32030976]
NPT21778 Single protein Sarcoplasmic/endoplasmic reticulum calcium ATPase 2 Homo sapiens IC50 = 2000.0 nM PMID[32030976]
NPT48 Individual protein Lysine-specific demethylase 4D-like Homo sapiens Potency = 2818.4 nM PubChem BioAssay data set
NPT888 Individual protein 78 kDa glucose-regulated protein Homo sapiens Potency n.a. 39810.7 nM PubChem BioAssay data set
NPT692 Individual protein Histone deacetylase 6 Homo sapiens Inhibition = 4.73 % HDAC6 screening dataset using tau-based substrate in an enzymatic assay yields selective inhibitors and activators
NPT51 Individual protein Microtubule-associated protein tau Homo sapiens Potency = 17782.8 nM PubChem BioAssay data set
NPT29454 Single protein Deoxynucleoside triphosphate triphosphohydrolase SAMHD1 Homo sapiens Inhibition = 1.635 % PMID[38318365]
NPT51 Individual protein Microtubule-associated protein tau Homo sapiens Potency = 7079.5 nM PubChem BioAssay data set
NPT51 Individual protein Microtubule-associated protein tau Homo sapiens Potency = 15848.9 nM PubChem BioAssay data set
NPT93 Individual protein Survival motor neuron protein Homo sapiens Potency = 11220.2 nM PubChem BioAssay data set
NPT792 Individual protein Arachidonate 15-lipoxygenase Homo sapiens Potency = 1000.0 nM PubChem BioAssay data set
NPT5 Individual protein Histone-lysine N-methyltransferase, H3 lysine-9 specific 3 Homo sapiens Potency n.a. 17782.8 nM PubChem BioAssay data set

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT28438 Unchecked Unchecked n.a. IC50 = 400.0 nM PMID[32030976]
NPT20555 Organism SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 Inhibition = 0.25 % Cytopathic SARS-Cov2 screening on VERO-E6 cells in a large repurposing effort
NPT28438 Unchecked Unchecked n.a. IC50 = 37210.0 nM PubChem BioAssay data set
NPT28438 Unchecked Unchecked n.a. Inhibition n.a. n.a. % PMID[21353727]
NPT28438 Unchecked Unchecked n.a. IC50 = 436515832.24 nM PMID[21353727]
NPT28438 Unchecked Unchecked n.a. IC50 = 130.0 nM PMID[21719297]
NPT20555 Organism SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 Inhibition = 50.55 % 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 = 400.0 nM PMID[19117760]
NPT28438 Unchecked Unchecked n.a. Potency = 15848.9 nM PubChem BioAssay data set
NPT28438 Unchecked Unchecked n.a. CC50 > 50000.0 nM PubChem BioAssay data set

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
- Rattus norvegicus NOAEL = 50.0 mg/kg-day ToxVal
- Rattus norvegicus LD50 <= 300.0 mg/kg ToxVal
- Rattus norvegicus LD50 >= 50.0 mg/kg ToxVal
- Rattus norvegicus LD50 > 2000.0 mg/kg ToxVal
- Mus musculus LD50 > 1800.0 mg/kg ToxVal
- Homo sapiens DNEL systemic = 0.822 mg/m3 ToxVal
- Homo sapiens PAC-3 = 110.0 mg/m3 ToxVal
- Homo sapiens PAC-2 = 69.0 mg/m3 ToxVal
- Homo sapiens PAC-1 = 6.3 mg/m3 ToxVal
- Homo sapiens MEG = 40.0 mg/m3 ToxVal
- Homo sapiens MEG = 250.0 mg/m3 ToxVal
- Homo sapiens MEG = 400.0 mg/m3 ToxVal

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 NPC602206 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
0.5652 Remote Similarity NPC180862
0.5652 Remote Similarity NPC600256
0.5455 Remote Similarity NPC269212
0.5417 Remote Similarity NPC33675
0.5217 Remote Similarity NPC306074

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC602206 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
0.5652 Remote Similarity NPD289 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