Natural Product: NPC136176

Natural Product IDNPC136176
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 CTSPAMFJBXKSOY-UHFFFAOYSA-O
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 5288156
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0000211] Indoles and derivatives
        • [CHEMONTID:0000210] Carbazoles

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 CTSPAMFJBXKSOY-UHFFFAOYSA-O
Standard InCHI InChI=1S/C17H14N2/c1-10-14-9-18-8-7-12(14)11(2)17-16(10)13-5-3-4-6-15(13)19-17/h3-9,19H,1-2H3/p+1
SMILES Cc1c2c[nH+]ccc2c(C)c2c1c1ccccc1[nH]2

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   246.12 Volume:   269.264
?
Van der Waals volume.
Dense:   0.914 LogP:   4.7
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.691
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.945
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   0.0 Rigid Bonds:   20.0
TPSA:   28.68
?
Topological Polar Surface Area.
 H-Bond Acceptor:   2.0
H-Bond Donor:   1.0 Rings:   4.0
Heavy Atoms:   2.0

MedChem Properties

QED Drug-Likeness Score:   0.486 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.295 Fsp3:   0.118
MCE-18:   20.0
?
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:   0.62 Fluc inhibitor:   0.815
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.943
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.452
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.012 Promiscuous compounds:   0.429

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.511 MDCK Permeability:   -4.496
Pgp-inhibitor:   0.035 Pgp-substrate:   0.451
PAMPA:   0.221
?
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%):   0.005 30% Bioavailability (F30%):   0.005
50% Bioavailability (F50%):   0.493

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.955 MRP1:   0.997
Plasma Protein Binding (PPB):   98.199% Volume Distribution (VD):   -0.113
Fu: 1.981%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.677
OATP1B3 inhibitor:   0.928 BCRP inhibitor:   0.367
BSEP inhibitor:   0.959

ADMET: Metabolism

CYP1A2-inhibitor:   0.993 CYP1A2-substrate:   0.989
CYP2C19-inhibitor:   0.024 CYP2C19-substrate:   0.381
CYP2C9-inhibitor:   0.991 CYP2C9-substrate:   0.998
CYP2D6-inhibitor:   0.99 CYP2D6-substrate:   1.0
CYP3A4-inhibitor:   0.992 CYP3A4-substrate:   0.994
CYP2B6-substrate:   0.001 CYP2C8-inhibitor:   1.0
HLM stability:   0.461
?
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):  7.148 Half-life (T1/2):  0.589

ADMET: Toxicity

hERG Blockers:  0.302 hERG Blockers (10um):  0.53
Human Hepatotoxicity (H-HT):  0.813 Drug-induced Liver Injury (DILI):  0.969
AMES Toxicity:  0.828 Rat Oral Acute Toxicity:  0.827
Maximum Recommended Daily Dose:  0.805 Skin Sensitization:  0.955
Carcinogencity:  0.893 Eye Corrosion:  0.003
Eye Irritation:  0.938 Respiratory Toxicity:  0.979
Drug-induced Neurotoxicity:  0.886 Ototoxicity:  0.626
Hematotoxicity:  0.545 Drug-induced Nephrotoxicity:  0.751
Genotoxicity:  0.288 RPMI-8226 Immunitoxicity:  0.165
A549 Cytotoxicity:  0.216 Hek293 Cytotoxicity:  0.487
BCF:   1.942
?
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:   4.009
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.653
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.558
?
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
NPO29314 Mangifera indica Species Anacardiaceae Eukaryota n.a. n.a. n.a. DOI[10.1246/bcsj.30.618]
NPO26650 Terminalia chebula Species Combretaceae Eukaryota n.a. n.a. n.a. PMID[11520216]
NPO15538 Eucalyptus citriodora Species Myrtaceae Eukaryota Leaves the campus of Panjab University, Chandigarh, India PMID[16989303]
NPO20598 Lythrum salicaria Species Lythraceae Eukaryota n.a. n.a. n.a. PMID[24459770]
NPO15538 Eucalyptus citriodora Species Myrtaceae Eukaryota Essential oil n.a. n.a. PMID[24641242]
NPO29314 Mangifera indica Species Anacardiaceae Eukaryota n.a. n.a. n.a. PMID[27466882]
NPO26277 Euphorbia hirta Species Euphorbiaceae Eukaryota n.a. n.a. n.a. PMID[32141299]
NPO31132 Eucalyptus citriodora Species Myrtaceae Eukaryota n.a. n.a. n.a. PMID[36840164]
NPO433 Geranium sibiricum Species Geraniaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3853 Aspidosperma subincanum Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18007.1 Agrimonia pilosa var. japonica Varieties Rosaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29314 Mangifera indica Species Anacardiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26277 Euphorbia hirta Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20598 Lythrum salicaria Species Lythraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO31132 Eucalyptus citriodora Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27675 Platycarya strobilacea Species Juglandaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO26650 Terminalia chebula Species Combretaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7667 Ochrosia elliptica Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29314 Mangifera indica Species Anacardiaceae Eukaryota n.a. n.a. Database[FooDB]
NPO29314 Mangifera indica Species Anacardiaceae Eukaryota Flower n.a. n.a. Database[FooDB]
NPO29314 Mangifera indica Species Anacardiaceae Eukaryota Fruit n.a. n.a. Database[FooDB]
NPO29314 Mangifera indica Species Anacardiaceae Eukaryota Leaf n.a. n.a. Database[FooDB]
NPO29314 Mangifera indica Species Anacardiaceae Eukaryota n.a. n.a. Database[FooDB]
NPO29314 Mangifera indica Species Anacardiaceae Eukaryota Seed n.a. n.a. Database[FooDB]
NPO433 Geranium sibiricum Species Geraniaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO26650 Terminalia chebula Species Combretaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO3853 Aspidosperma subincanum Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO20598 Lythrum salicaria Species Lythraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO7667 Ochrosia elliptica Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO27675 Platycarya strobilacea Species Juglandaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO31132 Eucalyptus citriodora Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO29314 Mangifera indica Species Anacardiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO26277 Euphorbia hirta Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO18007.1 Agrimonia pilosa var. japonica Varieties Rosaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO29314 Mangifera indica Species Anacardiaceae Eukaryota Fruits n.a. Database[Phenol-Explorer]
NPO26650 Terminalia chebula Species Combretaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO18007.1 Agrimonia pilosa var. japonica Varieties Rosaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO433 Geranium sibiricum Species Geraniaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO15538 Eucalyptus citriodora Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO20598 Lythrum salicaria Species Lythraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO7667 Ochrosia elliptica Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO26277 Euphorbia hirta Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO27675 Platycarya strobilacea Species Juglandaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO3853 Aspidosperma subincanum Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO29314 Mangifera indica Species Anacardiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO26650 Terminalia chebula Species Combretaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO29314 Mangifera indica Species Anacardiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO27675 Platycarya strobilacea Species Juglandaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO20598 Lythrum salicaria Species Lythraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO31132 Eucalyptus citriodora Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO26277 Euphorbia hirta Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO26650 Terminalia chebula Species Combretaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO15538 Eucalyptus citriodora Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3853 Aspidosperma subincanum Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26650 Terminalia chebula Species Combretaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7667 Ochrosia elliptica Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29314 Mangifera indica Species Anacardiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20598 Lythrum salicaria Species Lythraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26277 Euphorbia hirta Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27675 Platycarya strobilacea Species Juglandaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO433 Geranium sibiricum Species Geraniaceae 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 NPC136176 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
0.5085 Remote Similarity NPC215584

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC136176 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