Natural Product: NPC602656

Natural Product IDNPC602656
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 QYKQWFZDEDFELK-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL373777
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]

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 QYKQWFZDEDFELK-UHFFFAOYSA-N
Standard InCHI InChI=1S/C11H12N2S2/c1-15-11(14)13-7-8-6-12-10-5-3-2-4-9(8)10/h2-6,12H,7H2,1H3,(H,13,14)
SMILES CSC(=S)NCc1c[nH]c2ccccc12

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   236.04 Volume:   227.529
?
Van der Waals volume.
Dense:   1.037 LogP:   3.151
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.256
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.082
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   11.0
TPSA:   27.82
?
Topological Polar Surface Area.
 H-Bond Acceptor:   2.0
H-Bond Donor:   2.0 Rings:   2.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.785 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.319 Fsp3:   0.182
MCE-18:   10.0
?
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:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   1
Colloidal aggregators:   0.279 Fluc inhibitor:   0.001
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.104
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.39
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.114 Promiscuous compounds:   0.373

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.191 MDCK Permeability:   -4.699
Pgp-inhibitor:   0.999 Pgp-substrate:   0.0
PAMPA:   0.478
?
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):   0.942
20% Bioavailability (F20%):   0.814 30% Bioavailability (F30%):   1.0
50% Bioavailability (F50%):   0.989

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.036 MRP1:   0.121
Plasma Protein Binding (PPB):   97.182% Volume Distribution (VD):   -0.051
Fu: 1.472%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.0
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.097 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.856 CYP2C19-substrate:   0.999
CYP2C9-inhibitor:   0.072 CYP2C9-substrate:   0.985
CYP2D6-inhibitor:   0.011 CYP2D6-substrate:   0.949
CYP3A4-inhibitor:   0.604 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.131 CYP2C8-inhibitor:   1.0
HLM stability:   0.992
?
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):  7.989 Half-life (T1/2):  0.617

ADMET: Toxicity

hERG Blockers:  0.163 hERG Blockers (10um):  0.692
Human Hepatotoxicity (H-HT):  0.422 Drug-induced Liver Injury (DILI):  0.838
AMES Toxicity:  0.598 Rat Oral Acute Toxicity:  0.743
Maximum Recommended Daily Dose:  0.472 Skin Sensitization:  0.433
Carcinogencity:  0.776 Eye Corrosion:  0.001
Eye Irritation:  0.787 Respiratory Toxicity:  0.633
Drug-induced Neurotoxicity:  0.617 Ototoxicity:  0.282
Hematotoxicity:  0.214 Drug-induced Nephrotoxicity:  0.173
Genotoxicity:  0.849 RPMI-8226 Immunitoxicity:  0.055
A549 Cytotoxicity:  0.238 Hek293 Cytotoxicity:  0.46
BCF:   1.578
?
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:   4.067
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.4
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.902
?
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
NPO11120 Brassica rapa Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[21448706]
NPO11120 Brassica rapa Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[21856162]
NPO11120 Brassica rapa Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[23001436]
NPO7576 Brassica oleracea Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[24014097]
NPO7576 Brassica oleracea Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[24128451]
NPO11120 Brassica rapa Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[24868877]
NPO11120 Brassica rapa Species Brassicaceae Eukaryota n.a. aerial part n.a. PMID[24919480]
NPO11120 Brassica rapa Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[38202700]
NPO55008 Brassica oleracea capitata Genus Brassicaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7576 Brassica oleracea Species Brassicaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11120 Brassica rapa Species Brassicaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO30224 Brassica campestris Species Brassicaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO44623 Brassica napus L.ssp.rapifera Genus Brassicaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO58157 Brassica sativus Genus Brassicaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO53270 Brassica campestris L.subsp.pekinensis. Genus Brassicaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO61011 Brassica napa Genus Brassicaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7576 Brassica oleracea Species Brassicaceae Eukaryota n.a. n.a. Database[FooDB]
NPO7576 Brassica oleracea Species Brassicaceae Eukaryota Stem n.a. n.a. Database[FooDB]
NPO7576 Brassica oleracea Species Brassicaceae Eukaryota Sprout Seedling n.a. n.a. Database[FooDB]
NPO7576 Brassica oleracea Species Brassicaceae Eukaryota Shoot n.a. n.a. Database[FooDB]
NPO11120 Brassica rapa Species Brassicaceae Eukaryota Oil n.a. n.a. Database[FooDB]
NPO7576 Brassica oleracea Species Brassicaceae Eukaryota Leaf n.a. n.a. Database[FooDB]
NPO11120 Brassica rapa Species Brassicaceae Eukaryota n.a. n.a. Database[FooDB]
NPO11120 Brassica rapa Species Brassicaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO30224 Brassica campestris Species Brassicaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO7576 Brassica oleracea Species Brassicaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO11120 Brassica rapa Species Brassicaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO7576 Brassica oleracea Species Brassicaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO7576 Brassica oleracea Species Brassicaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO30224 Brassica campestris Species Brassicaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO11120 Brassica rapa Species Brassicaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7576 Brassica oleracea Species Brassicaceae 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
NPT1078 Individual protein Indoleamine 2,3-dioxygenase Homo sapiens Ki = 12000.0 nM PMID[21269836]
NPT1078 Individual protein Indoleamine 2,3-dioxygenase Homo sapiens Ki = 98000.0 nM PMID[23337802]
NPT1078 Individual protein Indoleamine 2,3-dioxygenase Homo sapiens Ki = 97700.0 nM PMID[33341650]
NPT1078 Individual protein Indoleamine 2,3-dioxygenase Homo sapiens Ki = 97700.0 nM PMID[16420054]
NPT199 Individual protein DNA polymerase kappa Homo sapiens Potency n.a. 44668.4 nM PubChem BioAssay data set
NPT67 Individual protein Cholinesterase Equus caballus Inhibition = -5.64 % PMID[23062825]
NPT66 Individual protein Acetylcholinesterase Electrophorus electricus Inhibition = -0.26 % PMID[23062825]
NPT51 Individual protein Microtubule-associated protein tau Homo sapiens Potency = 35481.3 nM PubChem BioAssay data set
NPT49 Individual protein DNA-(apurinic or apyrimidinic site) lyase Homo sapiens Potency n.a. 398.1 nM PubChem BioAssay data set
NPT442 Individual protein Ferritin light chain Equus caballus Potency = 35481.3 nM PubChem BioAssay data set
NPT442 Individual protein Ferritin light chain Equus caballus Potency = 28183.8 nM PubChem BioAssay data set

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT165 Cell line HeLa Homo sapiens IC50 > 100000.0 nM PMID[24012378]
NPT82 Cell line MDA-MB-231 Homo sapiens IC50 > 100000.0 nM PMID[24012378]
NPT83 Cell line MCF7 Homo sapiens IC50 > 100000.0 nM PMID[24012378]
NPT15 Cell line Jurkat Homo sapiens IC50 > 100000.0 nM PMID[24012378]
NPT165 Cell line HeLa Homo sapiens Inhibition = 25.2 % PMID[16997552]
NPT83 Cell line MCF7 Homo sapiens Inhibition = 21.5 % PMID[16997552]
NPT762 Cell line A-431 Homo sapiens Inhibition n.a. n.a. % PMID[16997552]
NPT111 Cell line K562 Homo sapiens IC50 = 128000.0 nM PMID[15780632]
NPT404 Cell line CCRF-CEM Homo sapiens IC50 = 90200.0 nM PMID[24012378]
NPT81 Cell line A549 Homo sapiens IC50 > 100000.0 nM PMID[24012378]
NPT28438 Unchecked Unchecked n.a. Activity = 111.0 % PMID[21292494]
NPT28438 Unchecked Unchecked n.a. Activity = 103.0 % PMID[21292494]
NPT28438 Unchecked Unchecked n.a. Activity = 38.0 % PMID[21292494]
NPT28438 Unchecked Unchecked n.a. Kcat/Km = 9896.0 /s/M PMID[21292494]
NPT28438 Unchecked Unchecked n.a. Activity = 108.0 % PMID[21292494]
NPT28438 Unchecked Unchecked n.a. Activity = 95.0 % PMID[21292494]
NPT28438 Unchecked Unchecked n.a. Kcat = 0.95 /s PMID[21292494]
NPT28438 Unchecked Unchecked n.a. Activity = 97.0 % PMID[21292494]
NPT28438 Unchecked Unchecked n.a. Activity = 17.0 % PMID[21292494]
NPT28438 Unchecked Unchecked n.a. Activity = 106.0 % PMID[21292494]
NPT28438 Unchecked Unchecked n.a. Activity = 835.0 mU/mg PMID[17616463]
NPT28438 Unchecked Unchecked n.a. Ratio = 4.0 n.a. PMID[21292494]
NPT28438 Unchecked Unchecked n.a. Activity = 100.0 % PMID[21292494]
NPT29781 Organism Plenodomus lingam Plenodomus lingam Inhibition = 100.0 % PMID[17616463]
NPT29781 Organism Plenodomus lingam Plenodomus lingam Inhibition = 45.0 % PMID[17616463]
NPT29781 Organism Plenodomus lingam Plenodomus lingam GI = 21.0 % PMID[22823278]
NPT29781 Organism Plenodomus lingam Plenodomus lingam GI = 55.0 % PMID[22823278]
NPT29781 Organism Plenodomus lingam Plenodomus lingam GI = 10.0 % PMID[22823278]
NPT29781 Organism Plenodomus lingam Plenodomus lingam Activity n.a. n.a. n.a. PMID[17616463]
NPT638 Organism Sclerotinia sclerotiorum Sclerotinia sclerotiorum Inhibition = 37.0 % PMID[17590338]
NPT638 Organism Sclerotinia sclerotiorum Sclerotinia sclerotiorum Inhibition = 100.0 % PMID[17590338]
NPT29533 Protein-protein interaction Menin/Histone-lysine N-methyltransferase MLL Homo sapiens Potency = 10000.0 nM PubChem BioAssay data set
NPT29533 Protein-protein interaction Menin/Histone-lysine N-methyltransferase MLL Homo sapiens Potency = 35481.3 nM PubChem BioAssay data set

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
Sclerotinia sclerotiorum n.a. T1/2 = 9.0 hr PMID[17590338]
Plenodomus lingam n.a. Drug recovery < 5.0 % PMID[22823278]
Plenodomus lingam n.a. Drug metabolism = 40.0 % PMID[22823278]





 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 NPC602656 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
0.587 Remote Similarity NPC138370
0.5217 Remote Similarity NPC300149
0.5217 Remote Similarity NPC42372
0.5098 Remote Similarity NPC67288
0.5098 Remote Similarity NPC310665
0.5094 Remote Similarity NPC74413

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC602656 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