Natural Product: NPC227320

Natural Product IDNPC227320
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 SRFCUPVBYYAMIL-IQUTYRLHSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 11869438
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0001253] Quinolines 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 SRFCUPVBYYAMIL-IQUTYRLHSA-N
Standard InCHI InChI=1S/C20H22N2O2/c1-3-13-12-22-9-7-14(13)10-19(22)20(23)16-6-8-21-18-5-4-15(24-2)11-17(16)18/h3-6,8,11,13-14,19H,1,7,9-10,12H2,2H3/t13-,14+,19+/m0/s1
SMILES C=C[C@H]1CN2CC[C@@H]1C[C@@H]2C(=O)c1ccnc2ccc(cc12)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   322.17 Volume:   341.369
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Van der Waals volume.
Dense:   0.944 LogP:   3.365
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.061
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.856
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The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   22.0
TPSA:   42.43
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   0.0 Rings:   5.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.64 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.388 Fsp3:   0.4
MCE-18:   73.5
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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:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.112 Fluc inhibitor:   0.115
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.317
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.088
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.002 Promiscuous compounds:   0.541

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.666 MDCK Permeability:   -4.858
Pgp-inhibitor:   1.0 Pgp-substrate:   0.994
PAMPA:   0.0
?
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%):   0.021 30% Bioavailability (F30%):   0.174
50% Bioavailability (F50%):   0.005

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.005 MRP1:   0.662
Plasma Protein Binding (PPB):   85.764% Volume Distribution (VD):   0.322
Fu: 17.286%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.074
OATP1B3 inhibitor:   0.004 BCRP inhibitor:   0.807
BSEP inhibitor:   0.018

ADMET: Metabolism

CYP1A2-inhibitor:   0.999 CYP1A2-substrate:   0.96
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.114
CYP2C9-inhibitor:   0.859 CYP2C9-substrate:   0.997
CYP2D6-inhibitor:   0.992 CYP2D6-substrate:   0.704
CYP3A4-inhibitor:   0.018 CYP3A4-substrate:   0.372
CYP2B6-substrate:   0.002 CYP2C8-inhibitor:   0.801
HLM stability:   0.974
?
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):  5.129 Half-life (T1/2):  1.356

ADMET: Toxicity

hERG Blockers:  0.608 hERG Blockers (10um):  0.592
Human Hepatotoxicity (H-HT):  0.618 Drug-induced Liver Injury (DILI):  0.919
AMES Toxicity:  0.656 Rat Oral Acute Toxicity:  0.674
Maximum Recommended Daily Dose:  0.863 Skin Sensitization:  0.157
Carcinogencity:  0.617 Eye Corrosion:  0.002
Eye Irritation:  0.725 Respiratory Toxicity:  0.962
Drug-induced Neurotoxicity:  0.944 Ototoxicity:  0.554
Hematotoxicity:  0.618 Drug-induced Nephrotoxicity:  0.909
Genotoxicity:  0.957 RPMI-8226 Immunitoxicity:  0.114
A549 Cytotoxicity:  0.376 Hek293 Cytotoxicity:  0.685
BCF:   1.469
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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:   3.903
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.149
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.68
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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
NPO25089 Cinchona calisaya Species Rubiaceae Eukaryota n.a. n.a. n.a. PMID[11992775]
NPO25089 Cinchona calisaya Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO30377 Cinchona ledgeriana Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO30377 Cinchona ledgeriana Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO8614 Cinchona succirubra Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO8614 Cinchona succirubra Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO25089 Cinchona calisaya Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO30377 Cinchona ledgeriana Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO8614 Cinchona succirubra Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25089 Cinchona calisaya Species Rubiaceae 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 NPC227320 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
0.6901 Remote Similarity NPC118832
0.6901 Remote Similarity NPC329708
0.5733 Remote Similarity NPC165349
0.5733 Remote Similarity NPC47059
0.5733 Remote Similarity NPC610890
0.5132 Remote Similarity NPC203754
0.5132 Remote Similarity NPC150048

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC227320 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
0.6901 Remote Similarity NPD4038 Phase 4
0.6901 Remote Similarity NPD4039 Phase 4
0.6806 Remote Similarity NPD4033 Approved
0.6806 Remote Similarity NPD4037 Approved
0.6447 Remote Similarity NPD31 Approved
0.6447 Remote Similarity NPD32 Approved
0.6447 Remote Similarity NPD4034 Approved
0.5733 Remote Similarity NPD4122 Pre-clinical
0.5568 Remote Similarity NPD4036 Approved
0.5435 Remote Similarity NPD4035 Approved

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