Natural Product: NPC605496

Natural Product IDNPC605496
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 JMBKXUYCBVKSSY-DOTOQJQBSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL202413
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 JMBKXUYCBVKSSY-DOTOQJQBSA-N
Standard InCHI InChI=1S/C17H22O3/c1-16(2)5-4-6-17(3)11-8-14(20)13(19)7-10(11)12(18)9-15(16)17/h7-8,15,19-20H,4-6,9H2,1-3H3/t15-,17+/m0/s1
SMILES CC1(C)CCC[C@]2(C)c3cc(O)c(O)cc3C(=O)C[C@@H]12

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   274.16 Volume:   292.744
?
Van der Waals volume.
Dense:   0.937 LogP:   2.801
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.775
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.551
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   0.0 Rigid Bonds:   17.0
TPSA:   57.53
?
Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   2.0 Rings:   3.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.708 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.522 Fsp3:   0.588
MCE-18:   73.889
?
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:   1 PAINS Alert:   1
Colloidal aggregators:   0.236 Fluc inhibitor:   0.256
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.571
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.031
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.507 Promiscuous compounds:   0.11

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.716 MDCK Permeability:   -4.666
Pgp-inhibitor:   0.079 Pgp-substrate:   0.001
PAMPA:   0.428
?
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):   0.02
20% Bioavailability (F20%):   0.734 30% Bioavailability (F30%):   0.913
50% Bioavailability (F50%):   0.997

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.225 MRP1:   0.823
Plasma Protein Binding (PPB):   97.116% Volume Distribution (VD):   0.221
Fu: 3.671%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   0.998 BCRP inhibitor:   0.791
BSEP inhibitor:   0.425

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.647
CYP2C19-inhibitor:   0.689 CYP2C19-substrate:   0.331
CYP2C9-inhibitor:   0.007 CYP2C9-substrate:   0.01
CYP2D6-inhibitor:   0.002 CYP2D6-substrate:   0.524
CYP3A4-inhibitor:   0.049 CYP3A4-substrate:   0.996
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.998
?
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):  16.374 Half-life (T1/2):  1.258

ADMET: Toxicity

hERG Blockers:  0.064 hERG Blockers (10um):  0.564
Human Hepatotoxicity (H-HT):  0.484 Drug-induced Liver Injury (DILI):  0.209
AMES Toxicity:  0.489 Rat Oral Acute Toxicity:  0.398
Maximum Recommended Daily Dose:  0.746 Skin Sensitization:  0.969
Carcinogencity:  0.604 Eye Corrosion:  0.228
Eye Irritation:  0.978 Respiratory Toxicity:  0.725
Drug-induced Neurotoxicity:  0.284 Ototoxicity:  0.442
Hematotoxicity:  0.267 Drug-induced Nephrotoxicity:  0.439
Genotoxicity:  0.241 RPMI-8226 Immunitoxicity:  0.037
A549 Cytotoxicity:  0.332 Hek293 Cytotoxicity:  0.266
BCF:   1.943
?
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:   4.698
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.103
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.597
?
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
NPO55543 Celastrus stehanotifolius Genus Celastraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]

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
NPT3887 Cell line CNE Homo sapiens IC50 = 22.1 ug.mL-1 PMID[16309905]
NPT165 Cell line HeLa Homo sapiens IC50 = 27.7 ug.mL-1 PMID[16309905]
NPT81 Cell line A549 Homo sapiens IC50 > 50.0 ug.mL-1 PMID[16309905]
NPT83 Cell line MCF7 Homo sapiens IC50 > 50.0 ug.mL-1 PMID[16309905]
NPT28438 Unchecked Unchecked n.a. IC50 = 11000.0 nM PMID[35367706]
NPT28438 Unchecked Unchecked n.a. IC50 = 6800.0 nM PMID[35367706]
NPT28438 Unchecked Unchecked n.a. IC50 = 850.0 nM PMID[35367706]
NPT28438 Unchecked Unchecked n.a. IC50 = 20000.0 nM PMID[35367706]
NPT28438 Unchecked Unchecked n.a. IC50 = 12000.0 nM PMID[35367706]
NPT28438 Unchecked Unchecked n.a. IC50 = 1600.0 nM PMID[35367706]
NPT28438 Unchecked Unchecked n.a. IC50 = 30000.0 nM PMID[35367706]
NPT28438 Unchecked Unchecked n.a. IC50 = 14000.0 nM PMID[35367706]

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 NPC605496 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
0.7143 Intermediate Similarity NPC69424
0.7 Intermediate Similarity NPC303910
0.7 Intermediate Similarity NPC176130
0.7 Intermediate Similarity NPC606689
0.6481 Remote Similarity NPC471851
0.5882 Remote Similarity NPC219573
0.5849 Remote Similarity NPC111845
0.5714 Remote Similarity NPC478646
0.5455 Remote Similarity NPC164295
0.5455 Remote Similarity NPC80443
0.5439 Remote Similarity NPC471853
0.5439 Remote Similarity NPC478653
0.5439 Remote Similarity NPC605657
0.5345 Remote Similarity NPC309169
0.5345 Remote Similarity NPC196941
0.5323 Remote Similarity NPC470035
0.5091 Remote Similarity NPC92079

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC605496 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