Natural Product: NPC19520

Natural Product IDNPC19520
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 SQAYCDKOCYEIQZ-AWEZNQCLSA-N
IUPAC Name n.a.
Synonyms TCMDC-138525
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL546282
PubChem CID 1549362
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000279] Alkaloids and derivatives
      • [CHEMONTID:0000381] Aporphines

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 SQAYCDKOCYEIQZ-AWEZNQCLSA-N
Standard InCHI InChI=1S/C21H23NO5/c1-22-6-5-11-7-16-20(27-10-26-16)18-12-9-15(23-2)21(25-4)19(24-3)13(12)8-14(22)17(11)18/h7,9,14H,5-6,8,10H2,1-4H3/t14-/m0/s1
SMILES CN1CCc2cc3c(c4-c5cc(c(c(c5C[C@H]1c24)OC)OC)OC)OCO3

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   369.16 Volume:   368.119
?
Van der Waals volume.
Dense:   1.003 LogP:   2.469
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.638
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.909
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   24.0
TPSA:   49.39
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   0.0 Rings:   5.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.828 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.289 Fsp3:   0.429
MCE-18:   90.0
?
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:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.327 Fluc inhibitor:   0.003
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.742
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.281
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.003 Promiscuous compounds:   0.897

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.732 MDCK Permeability:   -4.688
Pgp-inhibitor:   0.127 Pgp-substrate:   0.049
PAMPA:   0.031
?
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%):   0.147 30% Bioavailability (F30%):   0.032
50% Bioavailability (F50%):   0.972

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.999 MRP1:   0.979
Plasma Protein Binding (PPB):   75.926% Volume Distribution (VD):   0.273
Fu: 26.589%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.867
OATP1B3 inhibitor:   0.965 BCRP inhibitor:   0.636
BSEP inhibitor:   0.864

ADMET: Metabolism

CYP1A2-inhibitor:   0.997 CYP1A2-substrate:   0.015
CYP2C19-inhibitor:   0.999 CYP2C19-substrate:   0.003
CYP2C9-inhibitor:   0.526 CYP2C9-substrate:   0.999
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.917
CYP3A4-inhibitor:   0.983 CYP3A4-substrate:   0.926
CYP2B6-substrate:   1.0 CYP2C8-inhibitor:   0.0
HLM stability:   0.337
?
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):  6.512 Half-life (T1/2):  1.469

ADMET: Toxicity

hERG Blockers:  0.434 hERG Blockers (10um):  0.693
Human Hepatotoxicity (H-HT):  0.57 Drug-induced Liver Injury (DILI):  0.1
AMES Toxicity:  0.696 Rat Oral Acute Toxicity:  0.462
Maximum Recommended Daily Dose:  0.91 Skin Sensitization:  0.72
Carcinogencity:  0.836 Eye Corrosion:  0.0
Eye Irritation:  0.342 Respiratory Toxicity:  0.807
Drug-induced Neurotoxicity:  0.84 Ototoxicity:  0.485
Hematotoxicity:  0.253 Drug-induced Nephrotoxicity:  0.318
Genotoxicity:  0.399 RPMI-8226 Immunitoxicity:  0.097
A549 Cytotoxicity:  0.121 Hek293 Cytotoxicity:  0.449
BCF:   2.103
?
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:   4.21
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.417
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.152
?
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
NPO7891 Verbena littoralis Species n.a. n.a. n.a. n.a. n.a. PMID[11421751]
NPO7891 Verbena littoralis Species n.a. n.a. n.a. n.a. n.a. PMID[12762811]
NPO2099 Asteronyx loveni Species Asteronychidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2533 Cardamine amara Species Brassicaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24803 Hymenothrix wislizeni Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2681 Phillyrea latifolia Species Oleaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7891 Verbena littoralis Species n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO24769 Baptisia australis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2681 Phillyrea latifolia Species Oleaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO24769 Baptisia australis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO2681 Phillyrea latifolia Species Oleaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO24769 Baptisia australis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO7891 Verbena littoralis Species n.a. n.a. n.a. n.a. n.a. Database[TCMID]
NPO8039 Wikstroemia hainanensis Species Thymelaeaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7891 Verbena littoralis Species n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO5394 Litsea sericea Species Lauraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6146 Stereocaulon sterile Species Stereocaulaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2681 Phillyrea latifolia Species Oleaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2533 Cardamine amara Species Brassicaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2099 Asteronyx loveni Species Asteronychidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24002 Nassauvia uniflora Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23531 Valeriana ficariifolia Species Caprifoliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24769 Baptisia australis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24803 Hymenothrix wislizeni Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO478 Mazzaella laminarioides Species Gigartinaceae 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
NPT944 Individual protein Glucose transporter Leishmania mexicana Inhibition = 1.06 % DOI[10.6019/CHEMBL3433997]
NPT943 Individual protein Hexose transporter 1 Plasmodium falciparum Inhibition = 1.49 % DOI[10.6019/CHEMBL3433997]
NPT942 Individual protein Glucose transporter Homo sapiens Inhibition = -0.22 % DOI[10.6019/CHEMBL3433997]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT65 Cell line HepG2 Homo sapiens Inhibition = 7.0 % PMID[20485427]
NPT6 Organism Plasmodium falciparum Plasmodium falciparum XC50 = 968.77 nM PMID[20485427]
NPT6 Organism Plasmodium falciparum Plasmodium falciparum Inhibition = 0.0 % PMID[20485427]
NPT6 Organism Plasmodium falciparum Plasmodium falciparum Inhibition = 30.0 % PMID[20485427]
NPT6 Organism Plasmodium falciparum Plasmodium falciparum Inhibition = 84.0 % PMID[20485427]

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 NPC19520 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
0.7742 Intermediate Similarity NPC476432
0.7742 Intermediate Similarity NPC24264
0.7419 Intermediate Similarity NPC63997
0.7419 Intermediate Similarity NPC16805
0.7419 Intermediate Similarity NPC167546
0.6667 Remote Similarity NPC266753
0.6667 Remote Similarity NPC160298
0.6618 Remote Similarity NPC229166
0.6377 Remote Similarity NPC128560
0.6364 Remote Similarity NPC306902
0.6364 Remote Similarity NPC232924
0.6364 Remote Similarity NPC247389
0.6176 Remote Similarity NPC219341
0.6176 Remote Similarity NPC605845
0.6 Remote Similarity NPC298979
0.6 Remote Similarity NPC320223
0.6 Remote Similarity NPC600118
0.6 Remote Similarity NPC610764
0.5942 Remote Similarity NPC226102
0.5938 Remote Similarity NPC99659
0.5938 Remote Similarity NPC325871
0.5833 Remote Similarity NPC114364
0.5479 Remote Similarity NPC602113
0.5443 Remote Similarity NPC112248
0.5417 Remote Similarity NPC199465
0.5342 Remote Similarity NPC248642
0.5294 Remote Similarity NPC326316
0.5294 Remote Similarity NPC81733
0.5286 Remote Similarity NPC136508
0.5068 Remote Similarity NPC126284
0.5068 Remote Similarity NPC261206

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC19520 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