Natural Product: NPC239550

Natural Product IDNPC239550
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 MMPVUYPJIFYAEK-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 442350
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0002566] Isoquinolines and derivatives
        • [CHEMONTID:0000054] Benzylisoquinolines

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 MMPVUYPJIFYAEK-UHFFFAOYSA-N
Standard InCHI InChI=1S/C19H15NO6/c1-23-13-4-3-11(18(22)19(13)24-2)17(21)16-12-8-15-14(25-9-26-15)7-10(12)5-6-20-16/h3-8,22H,9H2,1-2H3
SMILES COc1ccc(C(=O)c2c3cc4c(cc3ccn2)OCO4)c(c1OC)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   353.09 Volume:   342.964
?
Van der Waals volume.
Dense:   1.03 LogP:   2.758
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.921
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.192
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   22.0
TPSA:   87.11
?
Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   1.0 Rings:   4.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.722 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.506 Fsp3:   0.158
MCE-18:   46.0
?
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:   1
Chelating Alert:   1 PAINS Alert:   0
Colloidal aggregators:   0.187 Fluc inhibitor:   0.371
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.51
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.376
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.024 Promiscuous compounds:   0.466

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.035 MDCK Permeability:   -4.755
Pgp-inhibitor:   0.498 Pgp-substrate:   0.011
PAMPA:   0.117
?
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):   0.008
20% Bioavailability (F20%):   0.006 30% Bioavailability (F30%):   0.002
50% Bioavailability (F50%):   0.372

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.094 MRP1:   0.274
Plasma Protein Binding (PPB):   96.589% Volume Distribution (VD):   -0.447
Fu: 3.086%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.971
OATP1B3 inhibitor:   0.998 BCRP inhibitor:   0.219
BSEP inhibitor:   0.988

ADMET: Metabolism

CYP1A2-inhibitor:   0.415 CYP1A2-substrate:   0.626
CYP2C19-inhibitor:   0.525 CYP2C19-substrate:   0.233
CYP2C9-inhibitor:   0.91 CYP2C9-substrate:   0.156
CYP2D6-inhibitor:   0.414 CYP2D6-substrate:   0.993
CYP3A4-inhibitor:   0.074 CYP3A4-substrate:   0.266
CYP2B6-substrate:   0.007 CYP2C8-inhibitor:   0.01
HLM stability:   0.263
?
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):  3.265 Half-life (T1/2):  1.129

ADMET: Toxicity

hERG Blockers:  0.247 hERG Blockers (10um):  0.513
Human Hepatotoxicity (H-HT):  0.651 Drug-induced Liver Injury (DILI):  0.927
AMES Toxicity:  0.739 Rat Oral Acute Toxicity:  0.394
Maximum Recommended Daily Dose:  0.672 Skin Sensitization:  0.332
Carcinogencity:  0.826 Eye Corrosion:  0.001
Eye Irritation:  0.877 Respiratory Toxicity:  0.817
Drug-induced Neurotoxicity:  0.731 Ototoxicity:  0.475
Hematotoxicity:  0.662 Drug-induced Nephrotoxicity:  0.784
Genotoxicity:  0.645 RPMI-8226 Immunitoxicity:  0.244
A549 Cytotoxicity:  0.437 Hek293 Cytotoxicity:  0.528
BCF:   1.184
?
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:   3.718
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.106
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.42
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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
NPO20891 Coleonema pulchellum Species Rutaceae Eukaryota n.a. Costa Rica; Bartica, Guyana n.a. PMID[16124770]
NPO20891 Coleonema pulchellum Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO22044 Tamarix chinensis Species Tamaricaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO22044 Tamarix chinensis Species Tamaricaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO22044 Tamarix chinensis Species Tamaricaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO20891 Coleonema pulchellum Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO22044 Tamarix chinensis Species Tamaricaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO22044 Tamarix chinensis Species Tamaricaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO20320 Cryptostegia madagascariensis Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21985 Koenigia coriaria Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20451 Vitex scabra Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20891 Coleonema pulchellum Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22625 Copris tripartitus Species Scarabaeidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22044 Tamarix chinensis Species Tamaricaceae 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 NPC239550 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
0.619 Remote Similarity NPC603917
0.5821 Remote Similarity NPC481438
0.5821 Remote Similarity NPC481437
0.5758 Remote Similarity NPC600003
0.5692 Remote Similarity NPC481459
0.5692 Remote Similarity NPC481460
0.5645 Remote Similarity NPC146976
0.5574 Remote Similarity NPC236668
0.5493 Remote Similarity NPC604282
0.5068 Remote Similarity NPC183537

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC239550 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