Natural Product: NPC606124

Natural Product IDNPC606124
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 RVGGCRQPGKFZDS-AKRYRNCVSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1426896
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 RVGGCRQPGKFZDS-AKRYRNCVSA-N
Standard InCHI InChI=1S/C24H26O7/c1-7-13(3)22(26)30-20-18-16(11-9-15-10-12-17(25)29-19(15)18)28-21(20)24(5,6)31-23(27)14(4)8-2/h7-12,20-21H,1-6H3/b13-7-,14-8-/t20-,21+/m1/s1
SMILES C/C=C(/C)C(=O)O[C@@H]1c2c(ccc3ccc(=O)oc23)O[C@@H]1C(C)(C)OC(=O)/C(C)=CC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   426.17 Volume:   435.794
?
Van der Waals volume.
Dense:   0.978 LogP:   3.833
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.444
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.263
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   7.0 Rigid Bonds:   20.0
TPSA:   92.04
?
Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   0.0 Rings:   3.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.398 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.067 Fsp3:   0.375
MCE-18:   71.788
?
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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.799 Fluc inhibitor:   0.101
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.739
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.688
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.329 Promiscuous compounds:   0.134

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.827 MDCK Permeability:   -4.677
Pgp-inhibitor:   0.007 Pgp-substrate:   0.002
PAMPA:   0.289
?
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%):   0.752 30% Bioavailability (F30%):   0.504
50% Bioavailability (F50%):   0.797

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.054 MRP1:   1.0
Plasma Protein Binding (PPB):   96.734% Volume Distribution (VD):   0.144
Fu: 3.337%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.992
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.0
BSEP inhibitor:   0.998

ADMET: Metabolism

CYP1A2-inhibitor:   0.292 CYP1A2-substrate:   0.998
CYP2C19-inhibitor:   0.279 CYP2C19-substrate:   0.953
CYP2C9-inhibitor:   0.993 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.001 CYP2D6-substrate:   0.784
CYP3A4-inhibitor:   0.981 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.018 CYP2C8-inhibitor:   0.999
HLM stability:   0.977
?
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):  6.058 Half-life (T1/2):  0.5

ADMET: Toxicity

hERG Blockers:  0.042 hERG Blockers (10um):  0.244
Human Hepatotoxicity (H-HT):  0.395 Drug-induced Liver Injury (DILI):  0.86
AMES Toxicity:  0.786 Rat Oral Acute Toxicity:  0.62
Maximum Recommended Daily Dose:  0.762 Skin Sensitization:  0.932
Carcinogencity:  0.909 Eye Corrosion:  0.339
Eye Irritation:  0.839 Respiratory Toxicity:  0.548
Drug-induced Neurotoxicity:  0.284 Ototoxicity:  0.118
Hematotoxicity:  0.391 Drug-induced Nephrotoxicity:  0.714
Genotoxicity:  0.979 RPMI-8226 Immunitoxicity:  0.117
A549 Cytotoxicity:  0.127 Hek293 Cytotoxicity:  0.357
BCF:   1.349
?
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:   4.489
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.854
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.636
?
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
NPO21056 Angelica keiskei Species Apiaceae Eukaryota exudates n.a. n.a. PMID[16441065]
NPO21056 Angelica keiskei Species Apiaceae Eukaryota stems n.a. n.a. PMID[18558745]
NPO21056 Angelica keiskei Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[21824777]
NPO21056 Angelica keiskei Species Apiaceae Eukaryota stems n.a. n.a. PMID[25891102]
NPO6190 Angelica archangelica Species Apiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21056 Angelica keiskei Species Apiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO62940 Angelica longeradiata Species Apiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO52312 Cnidium japonicum Species Apiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21056 Angelica keiskei Species Apiaceae Eukaryota n.a. n.a. Database[FooDB]
NPO6190 Angelica archangelica Species Apiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO21056 Angelica keiskei Species Apiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO6190 Angelica archangelica Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO21056 Angelica keiskei Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO6190 Angelica archangelica Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO6190 Angelica archangelica Species Apiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21056 Angelica keiskei Species Apiaceae 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
NPT151 Individual protein 15-hydroxyprostaglandin dehydrogenase [NAD+] Homo sapiens Potency = 10000.0 nM PubChem BioAssay data set
NPT154 Individual protein Mothers against decapentaplegic homolog 3 Homo sapiens Potency n.a. 35481.3 nM PubChem BioAssay data set
NPT161 Individual protein Rap guanine nucleotide exchange factor 4 Homo sapiens Potency n.a. 12589.3 nM PubChem BioAssay data set
NPT10 Individual protein Geminin Homo sapiens Potency n.a. 12995.3 nM PubChem BioAssay data set
NPT152 Individual protein Nuclear factor erythroid 2-related factor 2 Homo sapiens Potency n.a. 25929.0 nM PubChem BioAssay data set
NPT101 Individual protein Glucagon-like peptide 1 receptor Homo sapiens Potency n.a. 12589.3 nM PubChem BioAssay data set
NPT135 Individual protein Chromobox protein homolog 1 Homo sapiens Potency n.a. 70794.6 nM PubChem BioAssay data set
NPT11 Individual protein Guanine nucleotide-binding protein G(s), subunit alpha Homo sapiens Potency n.a. 17782.8 nM PubChem BioAssay data set
NPT267 Individual protein Neuropeptide Y receptor type 1 Homo sapiens IC50 = 5853.0 nM PubChem BioAssay data set
NPT1197 Individual protein Huntingtin Homo sapiens Potency = 35481.3 nM PubChem BioAssay data set
NPT50 Individual protein Tyrosyl-DNA phosphodiesterase 1 Homo sapiens Potency n.a. 29092.9 nM PubChem BioAssay data set
NPT531 Individual protein Nuclear receptor ROR-gamma Mus musculus Potency = 35481.3 nM PubChem BioAssay data set
NPT50 Individual protein Tyrosyl-DNA phosphodiesterase 1 Homo sapiens Potency n.a. 16360.1 nM PubChem BioAssay data set
NPT446 Individual protein Rap guanine nucleotide exchange factor 3 Homo sapiens Potency n.a. 79432.8 nM PubChem BioAssay data set
NPT94 Individual protein Aldehyde dehydrogenase 1A1 Homo sapiens Potency = 39810.7 nM PubChem BioAssay data set
NPT54 Individual protein Nonstructural protein 1 Influenza A virus Potency = 22387.2 nM PubChem BioAssay data set
NPT48 Individual protein Lysine-specific demethylase 4D-like Homo sapiens Potency = 39810.7 nM PubChem BioAssay data set
NPT51 Individual protein Microtubule-associated protein tau Homo sapiens Potency = 28183.8 nM PubChem BioAssay data set
NPT535 Individual protein Parathyroid hormone receptor Homo sapiens Potency n.a. 44668.4 nM PubChem BioAssay data set
NPT20859 Single protein Neuropeptide Y receptor type 2 Homo sapiens IC50 = 5058.0 nM PubChem BioAssay data set
NPT478 Individual protein Ataxin-2 Homo sapiens Potency n.a. 31622.8 nM PubChem BioAssay data set
NPT861 Individual protein Isocitrate dehydrogenase [NADP] cytoplasmic Homo sapiens Potency n.a. 29092.9 nM PubChem BioAssay data set
NPT59 Individual protein DNA polymerase beta Homo sapiens Potency = 79432.8 nM PubChem BioAssay data set
NPT64 Individual protein ATPase family AAA domain-containing protein 5 Homo sapiens Potency n.a. 29092.9 nM PubChem BioAssay data set
NPT56 Individual protein Beta-lactamase AmpC Escherichia coli K-12 Potency = 89125.1 nM PubChem BioAssay data set
NPT49 Individual protein DNA-(apurinic or apyrimidinic site) lyase Homo sapiens Potency n.a. 7943.3 nM PubChem BioAssay data set
NPT442 Individual protein Ferritin light chain Equus caballus Potency = 56234.1 nM PubChem BioAssay data set

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT71 Cell line HEK293 Homo sapiens Potency n.a. 18356.4 nM PubChem BioAssay data set
NPT28438 Unchecked Unchecked n.a. Potency n.a. 8912.5 nM PubChem BioAssay data set
NPT28438 Unchecked Unchecked n.a. Potency n.a. 11220.2 nM PubChem BioAssay data set
NPT6 Organism Plasmodium falciparum Plasmodium falciparum Potency n.a. 11689.1 nM PubChem BioAssay data set
NPT28438 Unchecked Unchecked n.a. EC50 = 15203.0 nM PubChem BioAssay data set
NPT28438 Unchecked Unchecked n.a. Concentration @ Maxi = 100.0 um PubChem BioAssay data set
NPT28438 Unchecked Unchecked n.a. Potency n.a. 16360.1 nM PubChem BioAssay data set
NPT28438 Unchecked Unchecked n.a. EC50 > 120000.0 nM PubChem BioAssay data set
NPT28438 Unchecked Unchecked n.a. Potency n.a. 2238.7 nM PubChem BioAssay data set
NPT6 Organism Plasmodium falciparum Plasmodium falciparum Potency n.a. 18526.0 nM PubChem BioAssay data set
NPT28438 Unchecked Unchecked n.a. Potency n.a. 25118.9 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

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 NPC606124 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
0.9333 High Similarity NPC307412
0.6812 Remote Similarity NPC84894
0.6812 Remote Similarity NPC18804
0.6812 Remote Similarity NPC319859
0.6812 Remote Similarity NPC164269
0.6812 Remote Similarity NPC198381
0.6812 Remote Similarity NPC287182
0.6812 Remote Similarity NPC127888
0.6471 Remote Similarity NPC55149
0.6429 Remote Similarity NPC195343
0.6429 Remote Similarity NPC267412
0.6429 Remote Similarity NPC74655
0.6081 Remote Similarity NPC471625
0.6 Remote Similarity NPC100986
0.5972 Remote Similarity NPC312881
0.5844 Remote Similarity NPC471630
0.5758 Remote Similarity NPC199204
0.5694 Remote Similarity NPC166672
0.5652 Remote Similarity NPC167111
0.5652 Remote Similarity NPC318400
0.5634 Remote Similarity NPC469675
0.5541 Remote Similarity NPC471910
0.5467 Remote Similarity NPC296624
0.5405 Remote Similarity NPC195357
0.5405 Remote Similarity NPC152771
0.5342 Remote Similarity NPC476457
0.5342 Remote Similarity NPC260265
0.5333 Remote Similarity NPC149320
0.5333 Remote Similarity NPC160727
0.5333 Remote Similarity NPC177281
0.527 Remote Similarity NPC86892
0.527 Remote Similarity NPC471909
0.5263 Remote Similarity NPC128529
0.5263 Remote Similarity NPC55615
0.5132 Remote Similarity NPC7526
0.5132 Remote Similarity NPC222036
0.5125 Remote Similarity NPC283019
0.5065 Remote Similarity NPC476455

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC606124 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