Natural Product: NPC220241

Natural Product IDNPC220241
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Arborinine
IUPAC Name 1-hydroxy-2,3-dimethoxy-10-methylacridin-9-one
Synonyms Arborinine
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL349609
PubChem CID 5281832
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0001253] Quinolines and derivatives
        • [CHEMONTID:0001908] Benzoquinolines
          • [CHEMONTID:0000274] Acridines
            • [CHEMONTID:0001811] Acridones

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 ATBZZQPALSPNMF-UHFFFAOYSA-N
Standard InCHI InChI=1S/C16H15NO4/c1-17-10-7-5-4-6-9(10)14(18)13-11(17)8-12(20-2)16(21-3)15(13)19/h4-8,19H,1-3H3
SMILES COc1cc2c(c(c1OC)O)c(=O)c1c(n2C)cccc1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   285.1 Volume:   287.325
?
Van der Waals volume.
Dense:   0.992 LogP:   2.191
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.178
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.82
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   17.0
TPSA:   60.69
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   1.0 Rings:   3.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.735 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.21 Fsp3:   0.188
MCE-18:   18.0
?
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:   1 PAINS Alert:   0
Colloidal aggregators:   0.154 Fluc inhibitor:   0.051
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.565
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.283
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.032 Promiscuous compounds:   0.186

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.01 MDCK Permeability:   -4.688
Pgp-inhibitor:   0.292 Pgp-substrate:   0.389
PAMPA:   0.229
?
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%):   0.004 30% Bioavailability (F30%):   0.01
50% Bioavailability (F50%):   0.359

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.589 MRP1:   0.971
Plasma Protein Binding (PPB):   97.222% Volume Distribution (VD):   -0.322
Fu: 2.612%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.879
OATP1B3 inhibitor:   0.969 BCRP inhibitor:   0.075
BSEP inhibitor:   0.551

ADMET: Metabolism

CYP1A2-inhibitor:   0.989 CYP1A2-substrate:   0.004
CYP2C19-inhibitor:   0.029 CYP2C19-substrate:   0.002
CYP2C9-inhibitor:   0.002 CYP2C9-substrate:   0.027
CYP2D6-inhibitor:   0.008 CYP2D6-substrate:   0.013
CYP3A4-inhibitor:   0.301 CYP3A4-substrate:   0.104
CYP2B6-substrate:   0.001 CYP2C8-inhibitor:   0.016
HLM stability:   0.801
?
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):  4.385 Half-life (T1/2):  1.188

ADMET: Toxicity

hERG Blockers:  0.182 hERG Blockers (10um):  0.571
Human Hepatotoxicity (H-HT):  0.686 Drug-induced Liver Injury (DILI):  0.707
AMES Toxicity:  0.683 Rat Oral Acute Toxicity:  0.435
Maximum Recommended Daily Dose:  0.494 Skin Sensitization:  0.578
Carcinogencity:  0.745 Eye Corrosion:  0.011
Eye Irritation:  0.8 Respiratory Toxicity:  0.792
Drug-induced Neurotoxicity:  0.846 Ototoxicity:  0.464
Hematotoxicity:  0.593 Drug-induced Nephrotoxicity:  0.523
Genotoxicity:  0.566 RPMI-8226 Immunitoxicity:  0.12
A549 Cytotoxicity:  0.273 Hek293 Cytotoxicity:  0.398
BCF:   1.252
?
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:   4.015
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.788
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.51
?
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
NPO3854 Ruta graveolens Species Rutaceae Eukaryota n.a. n.a. n.a. DOI[10.1042/BA20070200]
NPO25892 Tricleocarpa fragilis Species Galaxauraceae Eukaryota n.a. n.a. n.a. PMID[10691711]
NPO6049 Teclea trichocarpa Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[12141852]
NPO26262 Strychnos potatorum Species Loganiaceae Eukaryota n.a. n.a. n.a. PMID[12398531]
NPO3854 Ruta graveolens Species Rutaceae Eukaryota leaves n.a. n.a. PMID[12568545]
NPO17936 Glycosmis arborea Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[15387647]
NPO10019 Ilex oblonga Species Aquifoliaceae Eukaryota n.a. leaf n.a. PMID[17329884]
NPO3854 Ruta graveolens Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[19191562]
NPO15090 Zanthoxylum leprieurii Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[20413315]
NPO3854 Ruta graveolens Species Rutaceae Eukaryota Whole Plants n.a. n.a. PMID[28093914]
NPO3854 Ruta graveolens Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15090 Zanthoxylum leprieurii Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17936 Glycosmis arborea Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25892 Tricleocarpa fragilis Species Galaxauraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26262 Strychnos potatorum Species Loganiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10019 Ilex oblonga Species Aquifoliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26557 Daphne tangutica Species Thymelaeaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15180 Fusarium sulphureum Species Nectriaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO6049 Teclea trichocarpa Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4594 Vitellaria paradoxa Species Sapotaceae Eukaryota n.a. n.a. Database[FooDB]
NPO4594 Vitellaria paradoxa Species Sapotaceae Eukaryota n.a. n.a. Database[FooDB]
NPO3854 Ruta graveolens Species Rutaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO26557 Daphne tangutica Species Thymelaeaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO3854 Ruta graveolens Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO26447 Cassia singueana Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO3854 Ruta graveolens Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO26557 Daphne tangutica Species Thymelaeaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO15090 Zanthoxylum leprieurii Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26447 Cassia singueana Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13589 Prunus padus Species Rosaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6049 Teclea trichocarpa Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23886 Pachysandra axillaris Species Buxaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15180 Fusarium sulphureum Species Nectriaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17936 Glycosmis arborea Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1568 Allium ramosum Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8736 Bauerella simplicifolia n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO25650 Dacrydium fonkii Species Mytilidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25892 Tricleocarpa fragilis Species Galaxauraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26317 Cladosporium phlei Species Cladosporiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1833 Erigeron acris Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26400 Boronia anemonifolia Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10019 Ilex oblonga Species Aquifoliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4594 Vitellaria paradoxa Species Sapotaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1947 Nemopilema nomurai Species Rhizostomatidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26262 Strychnos potatorum Species Loganiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26557 Daphne tangutica Species Thymelaeaceae 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
NPT1315 Individual protein Adenosine A1 receptor Rattus norvegicus Ki = 12700.0 nM PMID[8576921]
NPT1316 Individual protein Adenosine A2a receptor Rattus norvegicus Ki = 6470.0 nM PMID[8576921]
NPT218 Individual protein Adenosine A3 receptor Homo sapiens Displacement = 63.0 % PMID[8576921]
NPT261 Individual protein Monoamine oxidase A Homo sapiens Inhibition = 23.67 % PMID[34915312]
NPT20576 Small molecule Heme n.a. IC50 = 42000.0 nM PMID[21600767]
NPT582 Individual protein Monoamine oxidase B Homo sapiens Inhibition = 31.0 % PMID[34915312]
NPT21762 Single protein Lysine-specific histone demethylase 1 Homo sapiens Inhibition = 99.33 % PMID[34915312]
NPT21762 Single protein Lysine-specific histone demethylase 1 Homo sapiens IC50 = 400.0 nM PMID[37014989]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT80 Cell line Raji Homo sapiens Activity > 80.0 % PMID[15387647]
NPT80 Cell line Raji Homo sapiens Activity = 60.0 % PMID[15387647]
NPT81 Cell line A549 Homo sapiens IC50 = 35000.0 nM PMID[20413315]
NPT579 Cell line DLD-1 Homo sapiens IC50 = 74000.0 nM PMID[20413315]
NPT762 Cell line A-431 Homo sapiens IC50 = 1840.0 nM PMID[35717872]
NPT515 Cell line SGC-7901 Homo sapiens IC50 = 1960.0 nM PMID[34915312]
NPT165 Cell line HeLa Homo sapiens IC50 = 1840.0 nM PMID[35717872]
NPT83 Cell line MCF7 Homo sapiens IC50 = 1840.0 nM PMID[35717872]
NPT6 Organism Plasmodium falciparum Plasmodium falciparum IC50 = 3850.0 nM PMID[12141852]
NPT28438 Unchecked Unchecked n.a. IC50 = 240.0 nM PMID[34915312]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 56000.0 nM PMID[20413315]
NPT485 Organism Plasmodium falciparum (isolate K1 / Thailand) Plasmodium falciparum K1 IC50 = 9340.0 nM PMID[12141852]
NPT2 Others Unspecified n.a. Activity = 2.7 % PMID[15387647]
NPT2 Others Unspecified n.a. Activity = 39.6 % PMID[15387647]
NPT2 Others Unspecified n.a. Activity = 74.3 % PMID[15387647]
NPT2 Others Unspecified n.a. Activity = 95.6 % PMID[15387647]

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 NPC220241 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
0.7059 Intermediate Similarity NPC118189
0.6923 Remote Similarity NPC182853
0.6863 Remote Similarity NPC206109
0.6154 Remote Similarity NPC295479
0.5962 Remote Similarity NPC298320
0.5962 Remote Similarity NPC223810
0.5741 Remote Similarity NPC114039
0.5556 Remote Similarity NPC45389
0.5455 Remote Similarity NPC134702
0.5294 Remote Similarity NPC204867
0.5185 Remote Similarity NPC268223

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC220241 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