Natural Product: NPC119575

Natural Product IDNPC119575
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 NHMDCMLCZRILTI-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 10236014
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0002448] Benzenoids
      • [CHEMONTID:0002279] Benzene and substituted derivatives
        • [CHEMONTID:0000321] Benzoyl 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 NHMDCMLCZRILTI-UHFFFAOYSA-N
Standard InCHI InChI=1S/C10H12O/c1-7-4-5-8(2)10(6-11)9(7)3/h4-6H,1-3H3
SMILES Cc1ccc(C)c(C=O)c1C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   148.09 Volume:   171.204
?
Van der Waals volume.
Dense:   0.865 LogP:   2.708
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.672
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.662
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   7.0
TPSA:   17.07
?
Topological Polar Surface Area.
 H-Bond Acceptor:   1.0
H-Bond Donor:   0.0 Rings:   1.0
Heavy Atoms:   1.0

MedChem Properties

QED Drug-Likeness Score:   0.559 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.108 Fsp3:   0.3
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:   Rejected GSK Rule:   Rejected
Golden Triangle Rule:   Accepted BMS Rule:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.047 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.041
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.001
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.997 Promiscuous compounds:   0.03

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.726 MDCK Permeability:   -4.703
Pgp-inhibitor:   0.968 Pgp-substrate:   0.281
PAMPA:   0.231
?
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):   0.003
20% Bioavailability (F20%):   0.242 30% Bioavailability (F30%):   0.234
50% Bioavailability (F50%):   0.788

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.912 MRP1:   0.969
Plasma Protein Binding (PPB):   93.435% Volume Distribution (VD):   0.05
Fu: 6.041%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.957
OATP1B3 inhibitor:   0.851 BCRP inhibitor:   0.129
BSEP inhibitor:   0.998

ADMET: Metabolism

CYP1A2-inhibitor:   0.905 CYP1A2-substrate:   0.992
CYP2C19-inhibitor:   0.961 CYP2C19-substrate:   0.227
CYP2C9-inhibitor:   0.601 CYP2C9-substrate:   0.289
CYP2D6-inhibitor:   0.517 CYP2D6-substrate:   0.347
CYP3A4-inhibitor:   0.966 CYP3A4-substrate:   0.099
CYP2B6-substrate:   0.728 CYP2C8-inhibitor:   0.613
HLM stability:   0.901
?
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):  9.986 Half-life (T1/2):  1.762

ADMET: Toxicity

hERG Blockers:  0.083 hERG Blockers (10um):  0.507
Human Hepatotoxicity (H-HT):  0.466 Drug-induced Liver Injury (DILI):  0.354
AMES Toxicity:  0.426 Rat Oral Acute Toxicity:  0.29
Maximum Recommended Daily Dose:  0.215 Skin Sensitization:  0.781
Carcinogencity:  0.668 Eye Corrosion:  0.994
Eye Irritation:  0.998 Respiratory Toxicity:  0.781
Drug-induced Neurotoxicity:  0.635 Ototoxicity:  0.215
Hematotoxicity:  0.317 Drug-induced Nephrotoxicity:  0.225
Genotoxicity:  0.14 RPMI-8226 Immunitoxicity:  0.045
A549 Cytotoxicity:  0.067 Hek293 Cytotoxicity:  0.09
BCF:   1.519
?
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:   3.837
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.616
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.555
?
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
NPO11438 Angelica gigas Species Apiaceae Eukaryota n.a. root n.a. PMID[11374978]
NPO11438 Angelica gigas Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[15679317]
NPO15462 Angelica sinensis Species Apiaceae Eukaryota roots purchased from Kiu Shun Trading Ltd., Vancouver, Canada 2000 PMID[16643021]
NPO11438 Angelica gigas Species Apiaceae Eukaryota n.a. root n.a. PMID[17997069]
NPO15462 Angelica sinensis Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[25538068]
NPO15462 Angelica sinensis Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[27400088]
NPO45707 Echinophora spinosa Genus Apiaceae Eukaryota n.a. n.a. n.a. PMID[30963429]
NPO15462 Angelica sinensis Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[36838931]
NPO42263 Ferulago glareosa Genus Apiaceae Eukaryota n.a. n.a. n.a. PMID[37070659]
NPO15462 Angelica sinensis Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[37480748]
NPO57072 Prangos trifida Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[38247600]
NPO15462 Angelica sinensis Species Apiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11438 Angelica gigas Species Apiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2921 Angelica acutiloba Species Apiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2921 Angelica acutiloba Species Apiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO11438 Angelica gigas Species Apiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO15462 Angelica sinensis Species Apiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO11438 Angelica gigas Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO2921 Angelica acutiloba Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO15462 Angelica sinensis Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO11438 Angelica gigas Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO2921 Angelica acutiloba Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO15462 Angelica sinensis Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO11438 Angelica gigas Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO15462 Angelica sinensis Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO2921 Angelica acutiloba Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO15462 Angelica sinensis Species Apiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2921 Angelica acutiloba Species Apiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11438 Angelica gigas 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
NPO42263 Ferulago glareosa Oil Roots 32.3 n.a. n.a. % PMID[37070659]
NPO42263 Ferulago glareosa Oil Aerial parts 0.9 n.a. n.a. % PMID[37070659]
NPO45707 Echinophora spinosa Oil n.a. 2.1±0.4 n.a. n.a. % PMID[30963429]
NPO57072 Prangos trifida Oil Roots 0.6 n.a. n.a. % PMID[38247600]
NPO57072 Prangos trifida Oil Leaves 0.8 n.a. n.a. % PMID[38247600]

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 NPC119575 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
NPC

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC119575 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