Natural Product: NPC606364

Natural Product IDNPC606364
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 QYCJAWYDGRZSTO-IRLTUAEKSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL2397731
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 QYCJAWYDGRZSTO-IRLTUAEKSA-N
Standard InCHI InChI=1S/C25H22O10/c1-33-17-6-10(2-4-14(17)28)23-13(9-26)19-12(3-5-15(29)25(19)35-23)24-22(32)21(31)20-16(30)7-11(27)8-18(20)34-24/h2-8,13,22-24,26-30,32H,9H2,1H3/t13-,22+,23+,24-/m1/s1
SMILES COc1cc([C@@H]2Oc3c(O)ccc([C@H]4Oc5cc(O)cc(O)c5C(=O)[C@@H]4O)c3[C@H]2CO)ccc1O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   482.12 Volume:   459.711
?
Van der Waals volume.
Dense:   1.049 LogP:   1.641
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.795
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.448
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   28.0
TPSA:   166.14
?
Topological Polar Surface Area.
 H-Bond Acceptor:   10.0
H-Bond Donor:   6.0 Rings:   5.0
Heavy Atoms:   10.0

MedChem Properties

QED Drug-Likeness Score:   0.325 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.227 Fsp3:   0.24
MCE-18:   101.0
?
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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   1
Chelating Alert:   1 PAINS Alert:   0
Colloidal aggregators:   0.756 Fluc inhibitor:   0.295
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.278
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.692
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.372 Promiscuous compounds:   0.21

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.352 MDCK Permeability:   -5.214
Pgp-inhibitor:   0.328 Pgp-substrate:   0.685
PAMPA:   0.636
?
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):   0.026
20% Bioavailability (F20%):   0.103 30% Bioavailability (F30%):   0.989
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.906
Plasma Protein Binding (PPB):   93.792% Volume Distribution (VD):   0.025
Fu: 5.749%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.978
BSEP inhibitor:   0.252

ADMET: Metabolism

CYP1A2-inhibitor:   0.645 CYP1A2-substrate:   0.004
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.309
CYP2C9-inhibitor:   0.851 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.056 CYP2D6-substrate:   0.237
CYP3A4-inhibitor:   0.41 CYP3A4-substrate:   0.996
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.0
?
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):  5.806 Half-life (T1/2):  2.309

ADMET: Toxicity

hERG Blockers:  0.055 hERG Blockers (10um):  0.368
Human Hepatotoxicity (H-HT):  0.952 Drug-induced Liver Injury (DILI):  0.747
AMES Toxicity:  0.817 Rat Oral Acute Toxicity:  0.615
Maximum Recommended Daily Dose:  0.458 Skin Sensitization:  0.999
Carcinogencity:  0.312 Eye Corrosion:  0.0
Eye Irritation:  0.946 Respiratory Toxicity:  0.683
Drug-induced Neurotoxicity:  0.304 Ototoxicity:  0.666
Hematotoxicity:  0.438 Drug-induced Nephrotoxicity:  0.818
Genotoxicity:  0.98 RPMI-8226 Immunitoxicity:  0.359
A549 Cytotoxicity:  0.968 Hek293 Cytotoxicity:  0.871
BCF:   0.856
?
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:   3.398
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.511
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.833
?
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
NPO5645 Silybum marianum Species Asteraceae Eukaryota n.a. n.a. n.a. DOI[10.1080/10496475.2013.791908]
NPO5645 Silybum marianum Species Asteraceae Eukaryota n.a. whole plant n.a. PMID[16394559]
NPO5645 Silybum marianum Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[24456525]
NPO5645 Silybum marianum Species Asteraceae Eukaryota Seeds n.a. n.a. PMID[24597776]
NPO5645 Silybum marianum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5645 Silybum marianum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO5645 Silybum marianum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO5645 Silybum marianum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO5645 Silybum marianum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO5645 Silybum marianum Species Asteraceae 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
NPT212 Individual protein Cytochrome P450 2C9 Homo sapiens Inhibition n.a. n.a. % PMID[23673225]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT1160 Cell line BJ Homo sapiens Activity n.a. n.a. n.a. PMID[28006905]
NPT83 Cell line MCF7 Homo sapiens Activity n.a. n.a. n.a. PMID[28006905]
NPT82 Cell line MDA-MB-231 Homo sapiens Activity n.a. n.a. n.a. PMID[28006905]
NPT111 Cell line K562 Homo sapiens Activity n.a. n.a. n.a. PMID[28006905]
NPT116 Cell line HL-60 Homo sapiens Activity n.a. n.a. n.a. PMID[28006905]
NPT2224 Cell line TERT-RPE1 Homo sapiens Activity n.a. n.a. n.a. PMID[28006905]
NPT2299 Cell line CAL-51 Homo sapiens Activity n.a. n.a. n.a. PMID[28006905]
NPT306 Cell line PC-3 Homo sapiens Activity n.a. n.a. n.a. PMID[28006905]
NPT65 Cell line HepG2 Homo sapiens Activity n.a. n.a. n.a. PMID[28006905]
NPT28833 No target No relevant target n.a. Activity = 1.74 equiv PMID[28006905]
NPT28833 No target No relevant target n.a. Activity = 0.65 equiv PMID[28006905]
NPT28833 No target No relevant target n.a. IC50 = 53110.0 nM PMID[28006905]
NPT28438 Unchecked Unchecked n.a. Activity n.a. n.a. n.a. PMID[28006905]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 > 130000.0 nM PMID[23673225]
NPT30103 Organism Hepatitis C virus Hepacivirus hominis Activity n.a. n.a. n.a. PMID[23673225]
NPT1593 Tissue Liver Rattus norvegicus IC50 = 36700.0 nM PMID[28006905]
NPT28784 Protein family Cytochrome P450 3A4/3A5 Homo sapiens Inhibition n.a. n.a. % PMID[23673225]

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
n.a. n.a. LogP = -0.47 n.a. PMID[28006905]





 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 NPC606364 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
0.7534 Intermediate Similarity NPC279209
0.7534 Intermediate Similarity NPC102277
0.7534 Intermediate Similarity NPC479117
0.7344 Intermediate Similarity NPC326037
0.7344 Intermediate Similarity NPC13858
0.6154 Remote Similarity NPC36916
0.6154 Remote Similarity NPC36
0.6154 Remote Similarity NPC7154
0.6154 Remote Similarity NPC125039
0.6154 Remote Similarity NPC7688
0.6076 Remote Similarity NPC138688
0.6076 Remote Similarity NPC72787
0.6076 Remote Similarity NPC217795
0.6076 Remote Similarity NPC58223
0.5802 Remote Similarity NPC602605
0.5797 Remote Similarity NPC320825
0.5758 Remote Similarity NPC62290
0.5758 Remote Similarity NPC142731
0.5758 Remote Similarity NPC326506
0.5588 Remote Similarity NPC44721
0.5588 Remote Similarity NPC211466
0.5588 Remote Similarity NPC605332
0.5571 Remote Similarity NPC52530
0.5522 Remote Similarity NPC279417
0.5522 Remote Similarity NPC49130
0.5507 Remote Similarity NPC36835
0.5507 Remote Similarity NPC246162
0.5507 Remote Similarity NPC9743
0.5507 Remote Similarity NPC260491
0.5507 Remote Similarity NPC61506
0.5507 Remote Similarity NPC240476
0.5507 Remote Similarity NPC250922
0.5362 Remote Similarity NPC306607
0.5294 Remote Similarity NPC4152
0.5278 Remote Similarity NPC236637
0.5147 Remote Similarity NPC21835
0.5143 Remote Similarity NPC606962
0.5139 Remote Similarity NPC16435
0.5072 Remote Similarity NPC208176

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC606364 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
0.6154 Remote Similarity NPD6166 Phase 2
0.6154 Remote Similarity NPD6167 Clinical (unspecified phase)
0.6154 Remote Similarity NPD6168 Clinical (unspecified phase)

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