Natural Product: NPC604461

Natural Product IDNPC604461
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 IPKKHRVROFYTEK-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1503330
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 IPKKHRVROFYTEK-UHFFFAOYSA-N
Standard InCHI InChI=1S/C18H26O4/c1-3-5-9-13-21-17(19)15-11-7-8-12-16(15)18(20)22-14-10-6-4-2/h7-8,11-12H,3-6,9-10,13-14H2,1-2H3
SMILES CCCCCOC(=O)c1ccccc1C(=O)OCCCCC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   306.18 Volume:   333.306
?
Van der Waals volume.
Dense:   0.919 LogP:   5.22
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.894
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.094
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The logarithm of aqueous solubility value.
Rotatable Bonds:   12.0 Rigid Bonds:   8.0
TPSA:   52.6
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   0.0 Rings:   1.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.475 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   1.8 Fsp3:   0.556
MCE-18:   7.0
?
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:   0.062 Fluc inhibitor:   0.056
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.048
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.172
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.927 Promiscuous compounds:   0.133

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.87 MDCK Permeability:   -4.703
Pgp-inhibitor:   0.07 Pgp-substrate:   0.012
PAMPA:   0.077
?
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):   0.007
20% Bioavailability (F20%):   0.448 30% Bioavailability (F30%):   0.4
50% Bioavailability (F50%):   0.184

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.462 MRP1:   0.989
Plasma Protein Binding (PPB):   95.937% Volume Distribution (VD):   0.571
Fu: 4.791%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.334
OATP1B3 inhibitor:   0.971 BCRP inhibitor:   0.031
BSEP inhibitor:   0.943

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   1.0
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.913
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.993
CYP3A4-inhibitor:   0.996 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.001 CYP2C8-inhibitor:   1.0
HLM stability:   1.0
?
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):  5.562 Half-life (T1/2):  0.415

ADMET: Toxicity

hERG Blockers:  0.451 hERG Blockers (10um):  0.904
Human Hepatotoxicity (H-HT):  0.014 Drug-induced Liver Injury (DILI):  0.467
AMES Toxicity:  0.012 Rat Oral Acute Toxicity:  0.031
Maximum Recommended Daily Dose:  0.033 Skin Sensitization:  0.493
Carcinogencity:  0.661 Eye Corrosion:  0.367
Eye Irritation:  0.996 Respiratory Toxicity:  0.038
Drug-induced Neurotoxicity:  0.083 Ototoxicity:  0.05
Hematotoxicity:  0.001 Drug-induced Nephrotoxicity:  0.028
Genotoxicity:  0.0 RPMI-8226 Immunitoxicity:  0.057
A549 Cytotoxicity:  0.039 Hek293 Cytotoxicity:  0.288
BCF:   1.455
?
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:   3.907
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.757
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.585
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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
NPO22730 Indigofera spicata Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[23895019]
NPO22730 Indigofera spicata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO22730 Indigofera spicata Species Fabaceae 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
NPT109 Individual protein Cytochrome P450 3A4 Homo sapiens Potency = 12589.3 nM PubChem BioAssay data set
NPT198 Individual protein Vitamin D receptor Homo sapiens Potency n.a. 2.8 nM PubChem BioAssay data set
NPT282 Individual protein MAP kinase ERK2 Homo sapiens Potency = 39810.7 nM PubChem BioAssay data set
NPT210 Individual protein Thyroid stimulating hormone receptor Homo sapiens Potency = 39810.7 nM PubChem BioAssay data set
NPT98 Individual protein HERG Homo sapiens Potency n.a. 39810.7 nM PubChem BioAssay data set
NPT539 Individual protein Cellular tumor antigen p53 Homo sapiens Potency = 7.9 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. Potency = 25118.9 nM PubChem BioAssay data set
NPT20596 Phenotype Hepatotoxicity n.a. Hepatotoxicity n.a. n.a. n.a. PMID[20843939]
NPT20596 Phenotype Hepatotoxicity n.a. Hepatotoxicity n.a. n.a. n.a. PMID[20553011]

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 LOEL = 1000.0 mg/kg-day ToxVal
- Rattus norvegicus NOEL = 200.0 mg/kg-day ToxVal
- Rattus norvegicus NOEL = 50.0 mg/kg-day 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 NPC604461 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
0.871 High Similarity NPC93084
0.871 High Similarity NPC251854
0.871 High Similarity NPC601045
0.8621 High Similarity NPC10251
0.7647 Intermediate Similarity NPC270699
0.7429 Intermediate Similarity NPC603245
0.6667 Remote Similarity NPC196246
0.6571 Remote Similarity NPC78701
0.641 Remote Similarity NPC604244
0.6333 Remote Similarity NPC119271
0.6176 Remote Similarity NPC608938
0.5789 Remote Similarity NPC305912
0.5789 Remote Similarity NPC1082
0.5758 Remote Similarity NPC214067
0.561 Remote Similarity NPC90522
0.5455 Remote Similarity NPC321852
0.5294 Remote Similarity NPC174099
0.525 Remote Similarity NPC604243
0.5143 Remote Similarity NPC92754
0.5122 Remote Similarity NPC607895

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC604461 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
0.8621 High Similarity NPD2182 Pre-clinical

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