Natural Product: NPC177002

Natural Product IDNPC177002
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 LQUGIUKHQGEKIC-SFHVURJKSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 101737129
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0002448] Benzenoids
      • [CHEMONTID:0002279] Benzene and substituted derivatives
        • [CHEMONTID:0000176] Benzoic acids and derivatives
          • [CHEMONTID:0001248] Hydroxybenzoic acid derivatives
            • [CHEMONTID:0000487] Salicylic acid and derivatives

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 LQUGIUKHQGEKIC-SFHVURJKSA-N
Standard InCHI InChI=1S/C18H22O4/c1-11(2)6-5-8-18(4)9-7-13-14(22-18)10-12(3)15(16(13)19)17(20)21/h6-7,9-10,19H,5,8H2,1-4H3,(H,20,21)/t18-/m0/s1
SMILES CC(=CCC[C@@]1(C)C=Cc2c(cc(C)c(c2O)C(=O)O)O1)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   302.15 Volume:   322.113
?
Van der Waals volume.
Dense:   0.938 LogP:   4.304
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.875
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.769
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   13.0
TPSA:   66.76
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   2.0 Rings:   2.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.813 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.473 Fsp3:   0.389
MCE-18:   49.28
?
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:   1 PAINS Alert:   0
Colloidal aggregators:   0.328 Fluc inhibitor:   0.103
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.597
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.408
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.444 Promiscuous compounds:   0.343

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.882 MDCK Permeability:   -4.716
Pgp-inhibitor:   0.036 Pgp-substrate:   0.006
PAMPA:   0.982
?
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):   0.012
20% Bioavailability (F20%):   0.135 30% Bioavailability (F30%):   0.156
50% Bioavailability (F50%):   0.807

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.049 MRP1:   0.991
Plasma Protein Binding (PPB):   97.972% Volume Distribution (VD):   -0.442
Fu: 1.633%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   0.979 BCRP inhibitor:   0.022
BSEP inhibitor:   0.808

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.001
CYP2C9-inhibitor:   0.186 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.037 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.347
HLM stability:   0.517
?
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):  2.39 Half-life (T1/2):  1.135

ADMET: Toxicity

hERG Blockers:  0.06 hERG Blockers (10um):  0.172
Human Hepatotoxicity (H-HT):  0.662 Drug-induced Liver Injury (DILI):  0.621
AMES Toxicity:  0.208 Rat Oral Acute Toxicity:  0.314
Maximum Recommended Daily Dose:  0.103 Skin Sensitization:  0.9
Carcinogencity:  0.305 Eye Corrosion:  0.117
Eye Irritation:  0.987 Respiratory Toxicity:  0.761
Drug-induced Neurotoxicity:  0.209 Ototoxicity:  0.554
Hematotoxicity:  0.301 Drug-induced Nephrotoxicity:  0.782
Genotoxicity:  0.061 RPMI-8226 Immunitoxicity:  0.062
A549 Cytotoxicity:  0.1 Hek293 Cytotoxicity:  0.036
BCF:   0.414
?
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:   3.219
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.745
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.978
?
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
NPO11872 Eleutherococcus senticosus Species Araliaceae Eukaryota n.a. leaf n.a. PMID[17125224]
NPO11872 Eleutherococcus senticosus Species Araliaceae Eukaryota leaves n.a. n.a. PMID[27400231]
NPO10454 Securiflustra securifrons Species Flustridae Eukaryota n.a. n.a. n.a. PMID[29220180]
NPO13081 Valeriana laxiflora Species Caprifoliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29208 Dictamnus albus Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10454 Securiflustra securifrons Species Flustridae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11872 Eleutherococcus senticosus Species Araliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13081 Valeriana laxiflora Species Caprifoliaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO7444 Clausena dentata Species Rutaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO29208 Dictamnus albus Species Rutaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO7444 Clausena dentata Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO13081 Valeriana laxiflora Species Caprifoliaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO29208 Dictamnus albus Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO11872 Eleutherococcus senticosus Species Araliaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO29208 Dictamnus albus Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO11872 Eleutherococcus senticosus Species Araliaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO10454 Securiflustra securifrons Species Flustridae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11872 Eleutherococcus senticosus Species Araliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7444 Clausena dentata Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29208 Dictamnus albus Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13081 Valeriana laxiflora Species Caprifoliaceae 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 NPC177002 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
0.9107 High Similarity NPC37139
0.9107 High Similarity NPC607595
0.7937 Intermediate Similarity NPC600538
0.7937 Intermediate Similarity NPC603652
0.7903 Intermediate Similarity NPC608840
0.7778 Intermediate Similarity NPC608841
0.7778 Intermediate Similarity NPC610040
0.7656 Intermediate Similarity NPC158866
0.7656 Intermediate Similarity NPC601888
0.7656 Intermediate Similarity NPC608372
0.7656 Intermediate Similarity NPC610065
0.7656 Intermediate Similarity NPC610100
0.7538 Intermediate Similarity NPC604977
0.7419 Intermediate Similarity NPC241976
0.6818 Remote Similarity NPC608709
0.6716 Remote Similarity NPC599921
0.6364 Remote Similarity NPC600521
0.5873 Remote Similarity NPC85895
0.5385 Remote Similarity NPC476006
0.5303 Remote Similarity NPC233059
0.5303 Remote Similarity NPC218753
0.5303 Remote Similarity NPC601175
0.5224 Remote Similarity NPC474481
0.5217 Remote Similarity NPC483636
0.5205 Remote Similarity NPC477691
0.5075 Remote Similarity NPC327457
0.5075 Remote Similarity NPC74137
0.5072 Remote Similarity NPC212965

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC177002 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