Natural Product: NPC603378

Natural Product IDNPC603378
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 ZDWSNKPLZUXBPE-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL321841
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 ZDWSNKPLZUXBPE-UHFFFAOYSA-N
Standard InCHI InChI=1S/C14H22O/c1-13(2,3)10-7-11(14(4,5)6)9-12(15)8-10/h7-9,15H,1-6H3
SMILES CC(C)(C)c1cc(O)cc(C(C)(C)C)c1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   206.17 Volume:   243.025
?
Van der Waals volume.
Dense:   0.848 LogP:   4.564
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.741
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.922
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The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   6.0
TPSA:   20.23
?
Topological Polar Surface Area.
 H-Bond Acceptor:   1.0
H-Bond Donor:   1.0 Rings:   1.0
Heavy Atoms:   1.0

MedChem Properties

QED Drug-Likeness Score:   0.68 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.097 Fsp3:   0.571
MCE-18:   12.0
?
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:   0.055 Fluc inhibitor:   0.213
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.001
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.0
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.982 Promiscuous compounds:   0.17

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.973 MDCK Permeability:   -4.762
Pgp-inhibitor:   0.982 Pgp-substrate:   0.101
PAMPA:   0.033
?
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):   0.257
20% Bioavailability (F20%):   0.699 30% Bioavailability (F30%):   0.76
50% Bioavailability (F50%):   0.988

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.006 MRP1:   0.163
Plasma Protein Binding (PPB):   86.183% Volume Distribution (VD):   0.292
Fu: 14.339%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   0.996 BCRP inhibitor:   0.017
BSEP inhibitor:   0.979

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.91
CYP2C19-inhibitor:   0.012 CYP2C19-substrate:   0.956
CYP2C9-inhibitor:   0.012 CYP2C9-substrate:   0.015
CYP2D6-inhibitor:   0.003 CYP2D6-substrate:   0.031
CYP3A4-inhibitor:   0.216 CYP3A4-substrate:   0.982
CYP2B6-substrate:   0.069 CYP2C8-inhibitor:   0.985
HLM stability:   0.859
?
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):  8.81 Half-life (T1/2):  0.489

ADMET: Toxicity

hERG Blockers:  0.246 hERG Blockers (10um):  0.859
Human Hepatotoxicity (H-HT):  0.276 Drug-induced Liver Injury (DILI):  0.136
AMES Toxicity:  0.083 Rat Oral Acute Toxicity:  0.332
Maximum Recommended Daily Dose:  0.685 Skin Sensitization:  0.587
Carcinogencity:  0.237 Eye Corrosion:  0.978
Eye Irritation:  0.997 Respiratory Toxicity:  0.656
Drug-induced Neurotoxicity:  0.631 Ototoxicity:  0.46
Hematotoxicity:  0.163 Drug-induced Nephrotoxicity:  0.156
Genotoxicity:  0.012 RPMI-8226 Immunitoxicity:  0.05
A549 Cytotoxicity:  0.74 Hek293 Cytotoxicity:  0.599
BCF:   2.562
?
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:   4.659
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.724
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.44
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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
NPO30295 Calotropis gigantea Species Apocynaceae Eukaryota leaves n.a. n.a. PMID[16933890]
NPO30295 Calotropis gigantea Species Apocynaceae Eukaryota n.a. root n.a. PMID[19052526]
NPO30295 Calotropis gigantea Species Apocynaceae Eukaryota n.a. n.a. n.a. PMID[28817274]
NPO30295 Calotropis gigantea Species Apocynaceae Eukaryota n.a. n.a. n.a. PMID[31967821]
NPO30295 Calotropis gigantea Species Apocynaceae Eukaryota n.a. n.a. n.a. PMID[32649211]
NPO58488 Baccaurea motleyana Species Phyllanthaceae Eukaryota n.a. n.a. n.a. PMID[38487168]
NPO47329 Merremia vitifolia Species Convolvulaceae Eukaryota n.a. n.a. n.a. PMID[39398064]
NPO30295 Calotropis gigantea Species Apocynaceae Eukaryota n.a. n.a. n.a. PMID[9548837]
NPO30295 Calotropis gigantea Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO44782 Streptomyces bacillaris strain RAM25C4 Genus Streptomycetaceae Bacteria 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
NPO47329 Merremia vitifolia n.a. n.a. 34.935 n.a. n.a. % PMID[39398064]
NPO58488 Baccaurea motleyana Methanolic extract n.a. 45.257 n.a. n.a. % PMID[38487168]

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
NPT28619 Protein complex GABA-A receptor; alpha-1/beta-2/gamma-2 Homo sapiens EC50 = 501187.23 nM PMID[12109905]
NPT28833 No target No relevant target n.a. CLogP = 5.1 n.a. PMID[12109905]
NPT28619 Protein complex GABA-A receptor; alpha-1/beta-2/gamma-2 Homo sapiens EC50 = 100000.0 nM PMID[12109905]
NPT28438 Unchecked Unchecked n.a. EC50 = 100000.0 nM PMID[19520579]
NPT693 Organism Xenopus laevis Xenopus laevis EC50 = 100000.0 nM PMID[12109905]

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 NPC603378 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
0.5652 Remote Similarity NPC269212
0.5417 Remote Similarity NPC211885
0.52 Remote Similarity NPC55903

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC603378 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