Natural Product: NPC320667

Natural Product IDNPC320667
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 CULUKMPMGVXCEI-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL66191
PubChem CID 234566
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000279] Alkaloids and derivatives
      • [CHEMONTID:0002719] Lupin alkaloids
        • [CHEMONTID:0002722] Cytisine 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 CULUKMPMGVXCEI-UHFFFAOYSA-N
Standard InCHI InChI=1S/C12H16N2O/c1-13-6-9-5-10(8-13)11-3-2-4-12(15)14(11)7-9/h2-4,9-10H,5-8H2,1H3
SMILES CN1CC2CC(C1)c1n(C2)c(=O)ccc1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   204.13 Volume:   213.313
?
Van der Waals volume.
Dense:   0.957 LogP:   0.628
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   0.7
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -0.226
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   0.0 Rigid Bonds:   16.0
TPSA:   25.24
?
Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   0.0 Rings:   3.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.627 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.937 Fsp3:   0.583
MCE-18:   54.474
?
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:   0 PAINS Alert:   0
Colloidal aggregators:   0.121 Fluc inhibitor:   0.003
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.159
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.588
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.046 Promiscuous compounds:   0.024

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.089 MDCK Permeability:   -5.153
Pgp-inhibitor:   0.008 Pgp-substrate:   0.057
PAMPA:   0.014
?
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%):   0.019 30% Bioavailability (F30%):   0.091
50% Bioavailability (F50%):   0.964

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   1.0 MRP1:   0.979
Plasma Protein Binding (PPB):   14.031% Volume Distribution (VD):   0.398
Fu: 85.085%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.344
OATP1B3 inhibitor:   0.591 BCRP inhibitor:   0.116
BSEP inhibitor:   0.612

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.024 CYP2C9-substrate:   0.011
CYP2D6-inhibitor:   0.219 CYP2D6-substrate:   0.001
CYP3A4-inhibitor:   0.832 CYP3A4-substrate:   0.001
CYP2B6-substrate:   0.541 CYP2C8-inhibitor:   0.0
HLM stability:   0.013
?
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):  12.379 Half-life (T1/2):  2.95

ADMET: Toxicity

hERG Blockers:  0.433 hERG Blockers (10um):  0.579
Human Hepatotoxicity (H-HT):  0.774 Drug-induced Liver Injury (DILI):  0.108
AMES Toxicity:  0.62 Rat Oral Acute Toxicity:  0.574
Maximum Recommended Daily Dose:  0.599 Skin Sensitization:  0.838
Carcinogencity:  0.602 Eye Corrosion:  0.573
Eye Irritation:  0.413 Respiratory Toxicity:  0.944
Drug-induced Neurotoxicity:  0.938 Ototoxicity:  0.6
Hematotoxicity:  0.678 Drug-induced Nephrotoxicity:  0.605
Genotoxicity:  0.848 RPMI-8226 Immunitoxicity:  0.098
A549 Cytotoxicity:  0.063 Hek293 Cytotoxicity:  0.215
BCF:   0.334
?
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:   2.94
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.248
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.461
?
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
NPO19231 Sophora flavescens Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[10654410]
NPO19231 Sophora flavescens Species Fabaceae Eukaryota n.a. root n.a. PMID[10843587]
NPO19231 Sophora flavescens Species Fabaceae Eukaryota Roots n.a. n.a. PMID[15568770]
NPO19231 Sophora flavescens Species Fabaceae Eukaryota n.a. root n.a. PMID[16392664]
NPO19231 Sophora flavescens Species Fabaceae Eukaryota n.a. root n.a. PMID[16933887]
NPO19231 Sophora flavescens Species Fabaceae Eukaryota roots Hualien Hsien, Taiwan 2003-JUL PMID[16933887]
NPO19231 Sophora flavescens Species Fabaceae Eukaryota n.a. root n.a. PMID[17951038]
NPO19231 Sophora flavescens Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[18175961]
NPO19231 Sophora flavescens Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[24295087]
NPO19231 Sophora flavescens Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[27575476]
NPO19231 Sophora flavescens Species Fabaceae Eukaryota Roots n.a. n.a. PMID[30298740]
NPO19231 Sophora flavescens Species Fabaceae Eukaryota Roots n.a. n.a. PMID[9868163]
NPO19231 Sophora flavescens Species Fabaceae Eukaryota n.a. root n.a. Database[Article]
NPO5995 Spartium junceum Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19231 Sophora flavescens Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29767 Cytisus laburnum Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5995 Spartium junceum Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO19231 Sophora flavescens Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO29767 Cytisus laburnum Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO5995 Spartium junceum Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO19231 Sophora flavescens Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO29767 Cytisus laburnum Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO5995 Spartium junceum Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO19231 Sophora flavescens Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO19231 Sophora flavescens Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO5995 Spartium junceum Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19231 Sophora flavescens Species Fabaceae 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
NPT412 Protein complex Neuronal acetylcholine receptor; alpha4/beta2 Rattus norvegicus Ki = 5.754 nM PMID[12747776]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT367 Cell line MDA-N Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT368 Cell line SN12C Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT369 Cell line ACHN Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT370 Cell line NCI-H23 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT371 Cell line UO-31 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT372 Cell line HOP-92 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT90 Cell line DU-145 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT373 Cell line SK-MEL-5 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT375 Cell line Malme-3M Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT377 Cell line OVCAR-3 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT379 Cell line HOP-62 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT378 Cell line NCI/ADR-RES Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT381 Cell line OVCAR-8 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT380 Cell line U-251 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT382 Cell line OVCAR-5 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT383 Cell line SNB-19 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT82 Cell line MDA-MB-231 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT384 Cell line TK-10 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT386 Cell line KM12 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT455 Cell line NCI-H522 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT387 Cell line M14 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT388 Cell line NCI-H322M Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT456 Cell line OVCAR-4 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT390 Cell line LOX IMVI Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT457 Cell line BT-549 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT147 Cell line SK-MEL-2 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT391 Cell line HCC 2998 Homo sapiens GI50 n.a. 252.93 nM PubChem BioAssay data set
NPT81 Cell line A549 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT392 Cell line SNB-75 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT393 Cell line HCT-116 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT148 Cell line HCT-15 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT394 Cell line EKVX Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT395 Cell line SF-268 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT306 Cell line PC-3 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT83 Cell line MCF7 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT146 Cell line SK-OV-3 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT397 Cell line NCI-H460 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT396 Cell line T47D Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT398 Cell line UACC-62 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT308 Cell line CAKI-1 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT400 Cell line MDA-MB-435 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT458 Cell line IGROV-1 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT399 Cell line SF-295 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT401 Cell line 786-0 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT402 Cell line Hs-578T Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT403 Cell line UACC-257 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT139 Cell line HT-29 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT407 Cell line COLO 205 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT406 Cell line RXF 393 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT616 Cell line MDCK Canis lupus familiaris CC50 > 80000.0 nM PMID[25147619]
NPT1453 Organism Influenza A virus (A/PR/8/34(H1N1)) Influenza A virus (A/Puerto Rico/8/1934(H1N1)) EC50 > 80000.0 nM PMID[25147619]

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
- Mus musculus LD50 = 3.602640791 mg/kg TOXRIC

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 NPC320667 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
1.0 High Similarity NPC214125
0.7037 Intermediate Similarity NPC604550
0.6909 Remote Similarity NPC609084
0.55 Remote Similarity NPC78058
0.55 Remote Similarity NPC135639

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC320667 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