Natural Product: NPC65352

Natural Product IDNPC65352
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 RRRDBTILCQKUOK-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 10643200
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0000211] Indoles and derivatives
        • [CHEMONTID:0002497] Indoles
          • [CHEMONTID:0004196] 3-alkylindoles

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 RRRDBTILCQKUOK-UHFFFAOYSA-N
Standard InCHI InChI=1S/C26H21N3/c1-26(20-14-27-23-11-5-2-8-17(20)23,21-15-28-24-12-6-3-9-18(21)24)22-16-29-25-13-7-4-10-19(22)25/h2-16,27-29H,1H3
SMILES CC(c1c[nH]c2ccccc12)(c1c[nH]c2ccccc12)c1c[nH]c2ccccc12

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   375.17 Volume:   408.266
?
Van der Waals volume.
Dense:   0.919 LogP:   5.492
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   4.111
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -6.932
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   30.0
TPSA:   47.37
?
Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   3.0 Rings:   6.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.317 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.425 Fsp3:   0.077
MCE-18:   30.0
?
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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.999 Fluc inhibitor:   0.448
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.247
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.867
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.289 Promiscuous compounds:   0.228

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.891 MDCK Permeability:   -4.695
Pgp-inhibitor:   0.539 Pgp-substrate:   0.083
PAMPA:   0.053
?
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%):   0.0 30% Bioavailability (F30%):   0.255
50% Bioavailability (F50%):   0.596

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.979 MRP1:   0.752
Plasma Protein Binding (PPB):   97.804% Volume Distribution (VD):   0.255
Fu: 1.944%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.87
OATP1B3 inhibitor:   0.93 BCRP inhibitor:   0.925
BSEP inhibitor:   0.997

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   1.0
CYP2C9-inhibitor:   0.999 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.042 CYP2D6-substrate:   1.0
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   1.0 CYP2C8-inhibitor:   1.0
HLM stability:   1.0
?
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):  7.416 Half-life (T1/2):  0.53

ADMET: Toxicity

hERG Blockers:  0.262 hERG Blockers (10um):  0.685
Human Hepatotoxicity (H-HT):  0.666 Drug-induced Liver Injury (DILI):  0.603
AMES Toxicity:  0.621 Rat Oral Acute Toxicity:  0.663
Maximum Recommended Daily Dose:  0.708 Skin Sensitization:  0.125
Carcinogencity:  0.551 Eye Corrosion:  0.013
Eye Irritation:  0.952 Respiratory Toxicity:  0.739
Drug-induced Neurotoxicity:  0.899 Ototoxicity:  0.447
Hematotoxicity:  0.35 Drug-induced Nephrotoxicity:  0.562
Genotoxicity:  0.572 RPMI-8226 Immunitoxicity:  0.054
A549 Cytotoxicity:  0.277 Hek293 Cytotoxicity:  0.316
BCF:   2.241
?
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:   4.343
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.972
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.997
?
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
NPO10405 Beilschmiedia zenkeri Species Lauraceae Eukaryota stem bark n.a. n.a. PMID[19904919]
NPO10405 Beilschmiedia zenkeri Species Lauraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10405 Beilschmiedia zenkeri Species Lauraceae 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 NPC65352 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
0.6216 Remote Similarity NPC53947
0.6 Remote Similarity NPC261195
0.5946 Remote Similarity NPC216643
0.5946 Remote Similarity NPC288838
0.5946 Remote Similarity NPC601214
0.5789 Remote Similarity NPC105127
0.5789 Remote Similarity NPC102423
0.5789 Remote Similarity NPC300149
0.5789 Remote Similarity NPC42372
0.5789 Remote Similarity NPC230002
0.561 Remote Similarity NPC29886
0.561 Remote Similarity NPC72435
0.561 Remote Similarity NPC604154
0.55 Remote Similarity NPC131718
0.55 Remote Similarity NPC96102
0.5366 Remote Similarity NPC230869
0.5366 Remote Similarity NPC138370
0.5366 Remote Similarity NPC279081
0.5238 Remote Similarity NPC601179
0.5116 Remote Similarity NPC84911
0.5116 Remote Similarity NPC154339
0.5116 Remote Similarity NPC608908
0.5111 Remote Similarity NPC603879

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC65352 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
0.55 Remote Similarity NPD198 Clinical (unspecified phase)
0.5227 Remote Similarity NPD786 Pre-clinical

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