Natural Product: NPC603989

Natural Product IDNPC603989
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 DZXMJUKEEAOGQU-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL472432
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 DZXMJUKEEAOGQU-UHFFFAOYSA-N
Standard InCHI InChI=1S/C17H20O4/c1-19-14-8-13(9-15(11-14)20-2)5-4-12-6-7-16(18)17(10-12)21-3/h6-11,18H,4-5H2,1-3H3
SMILES COc1cc(CCc2ccc(O)c(OC)c2)cc(OC)c1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   288.14 Volume:   304.817
?
Van der Waals volume.
Dense:   0.945 LogP:   3.33
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.248
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.067
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   12.0
TPSA:   47.92
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   1.0 Rings:   2.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.886 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   1.857 Fsp3:   0.294
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:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   1 PAINS Alert:   0
Colloidal aggregators:   0.288 Fluc inhibitor:   0.024
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.04
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.235
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.661 Promiscuous compounds:   0.538

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.948 MDCK Permeability:   -4.73
Pgp-inhibitor:   0.988 Pgp-substrate:   0.033
PAMPA:   0.001
?
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):   0.095
20% Bioavailability (F20%):   0.434 30% Bioavailability (F30%):   0.371
50% Bioavailability (F50%):   0.925

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.005 MRP1:   0.182
Plasma Protein Binding (PPB):   88.199% Volume Distribution (VD):   -0.066
Fu: 9.355%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   0.851
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.988
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.688
CYP2C9-inhibitor:   1.0 CYP2C9-substrate:   0.998
CYP2D6-inhibitor:   0.999 CYP2D6-substrate:   1.0
CYP3A4-inhibitor:   0.036 CYP3A4-substrate:   0.881
CYP2B6-substrate:   0.293 CYP2C8-inhibitor:   1.0
HLM stability:   0.824
?
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):  9.534 Half-life (T1/2):  1.019

ADMET: Toxicity

hERG Blockers:  0.475 hERG Blockers (10um):  0.804
Human Hepatotoxicity (H-HT):  0.588 Drug-induced Liver Injury (DILI):  0.214
AMES Toxicity:  0.582 Rat Oral Acute Toxicity:  0.162
Maximum Recommended Daily Dose:  0.478 Skin Sensitization:  0.705
Carcinogencity:  0.387 Eye Corrosion:  0.292
Eye Irritation:  0.906 Respiratory Toxicity:  0.682
Drug-induced Neurotoxicity:  0.521 Ototoxicity:  0.499
Hematotoxicity:  0.374 Drug-induced Nephrotoxicity:  0.566
Genotoxicity:  0.056 RPMI-8226 Immunitoxicity:  0.12
A549 Cytotoxicity:  0.402 Hek293 Cytotoxicity:  0.554
BCF:   1.628
?
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:   4.116
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.203
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.619
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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
NPO23721 Epidendrum rigidum Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23721 Epidendrum rigidum Species Orchidaceae 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
NPT549 Individual protein Calmodulin Bos taurus Activity n.a. n.a. n.a. PMID[14987052]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT548 Tissue Ileum Cavia porcellus IC50 = 1390.0 nM PMID[14987052]
NPT548 Tissue Ileum Cavia porcellus Emax = 76.4 % PMID[14987052]
NPT548 Tissue Ileum Cavia porcellus Ratio IC50 = 3.05 n.a. PMID[14987052]

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 NPC603989 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
0.7778 Intermediate Similarity NPC193544
0.7368 Intermediate Similarity NPC57490
0.7073 Intermediate Similarity NPC117214
0.7027 Intermediate Similarity NPC474933
0.6829 Remote Similarity NPC203133
0.675 Remote Similarity NPC197757
0.6667 Remote Similarity NPC136319
0.6667 Remote Similarity NPC156840
0.65 Remote Similarity NPC475169
0.6316 Remote Similarity NPC257124
0.6154 Remote Similarity NPC8547
0.6154 Remote Similarity NPC221049
0.6154 Remote Similarity NPC140359
0.6098 Remote Similarity NPC71579
0.6087 Remote Similarity NPC472091
0.6 Remote Similarity NPC165133
0.6 Remote Similarity NPC242885
0.6 Remote Similarity NPC95614
0.6 Remote Similarity NPC471693
0.6 Remote Similarity NPC232316
0.5952 Remote Similarity NPC69261
0.5854 Remote Similarity NPC255675
0.575 Remote Similarity NPC294327
0.5714 Remote Similarity NPC85488
0.5714 Remote Similarity NPC603326
0.5641 Remote Similarity NPC2682
0.5625 Remote Similarity NPC472090
0.5581 Remote Similarity NPC17943
0.5581 Remote Similarity NPC299406
0.5526 Remote Similarity NPC299759
0.55 Remote Similarity NPC475961
0.5405 Remote Similarity NPC7097
0.5385 Remote Similarity NPC293619
0.5366 Remote Similarity NPC233410
0.5349 Remote Similarity NPC75440
0.5333 Remote Similarity NPC194416
0.5333 Remote Similarity NPC31344
0.5333 Remote Similarity NPC177291
0.5333 Remote Similarity NPC317769
0.5333 Remote Similarity NPC312675
0.5333 Remote Similarity NPC262156
0.5333 Remote Similarity NPC127937
0.5333 Remote Similarity NPC184651
0.5333 Remote Similarity NPC113865
0.5306 Remote Similarity NPC282000
0.5217 Remote Similarity NPC66518
0.5217 Remote Similarity NPC56214
0.5217 Remote Similarity NPC487676
0.5217 Remote Similarity NPC476968
0.5208 Remote Similarity NPC74817
0.5116 Remote Similarity NPC251855
0.5116 Remote Similarity NPC472093
0.5106 Remote Similarity NPC51840
0.5106 Remote Similarity NPC227217
0.5106 Remote Similarity NPC117780
0.5106 Remote Similarity NPC82679
0.5102 Remote Similarity NPC311680
0.5102 Remote Similarity NPC114298
0.5091 Remote Similarity NPC472087

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC603989 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
0.6316 Remote Similarity NPD228 Phase 0

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