Natural Product: NPC245836

Natural Product IDNPC245836
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 STECJAGHUSJQJN-VJQRDGCPSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL3084722
PubChem CID NA
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000264] Organic acids and derivatives
      • [CHEMONTID:0000472] Hydroxy acids and derivatives
        • [CHEMONTID:0001713] Beta hydroxy acids and derivatives

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 STECJAGHUSJQJN-VJQRDGCPSA-N
Standard InCHI InChI=1S/C17H21NO4/c1-18-13-7-11(8-14(18)16-15(13)22-16)21-17(20)12(9-19)10-5-3-2-4-6-10/h2-6,11-16,19H,7-9H2,1H3/t11-,12-,13+,14-,15+,16-/m1/s1
SMILES OC[C@H](c1ccccc1)C(=O)O[C@@H]1C[C@@H]2N([C@H](C1)[C@@H]1[C@H]2O1)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   303.15 Volume:   303.974
?
Van der Waals volume.
Dense:   0.997 LogP:   1.046
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   0.279
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -0.911
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   18.0
TPSA:   62.3
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   1.0 Rings:   4.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.662 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.733 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:   0 PAINS Alert:   0
Colloidal aggregators:   0.506 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.027
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.08
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.016 Promiscuous compounds:   0.712

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.954 MDCK Permeability:   -4.86
Pgp-inhibitor:   0.001 Pgp-substrate:   0.488
PAMPA:   0.926
?
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):   0.0
20% Bioavailability (F20%):   0.001 30% Bioavailability (F30%):   0.216
50% Bioavailability (F50%):   0.75

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.013 MRP1:   0.293
Plasma Protein Binding (PPB):   30.305% Volume Distribution (VD):   0.295
Fu: 64.803%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.961
OATP1B3 inhibitor:   0.987 BCRP inhibitor:   0.054
BSEP inhibitor:   0.001

ADMET: Metabolism

CYP1A2-inhibitor:   0.003 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.015 CYP2C19-substrate:   0.002
CYP2C9-inhibitor:   0.101 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.973 CYP3A4-substrate:   0.026
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.002
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):  14.032 Half-life (T1/2):  2.077

ADMET: Toxicity

hERG Blockers:  0.083 hERG Blockers (10um):  0.118
Human Hepatotoxicity (H-HT):  0.813 Drug-induced Liver Injury (DILI):  0.559
AMES Toxicity:  0.519 Rat Oral Acute Toxicity:  0.184
Maximum Recommended Daily Dose:  0.633 Skin Sensitization:  0.993
Carcinogencity:  0.056 Eye Corrosion:  0.014
Eye Irritation:  0.806 Respiratory Toxicity:  0.422
Drug-induced Neurotoxicity:  0.774 Ototoxicity:  0.49
Hematotoxicity:  0.178 Drug-induced Nephrotoxicity:  0.579
Genotoxicity:  0.772 RPMI-8226 Immunitoxicity:  0.045
A549 Cytotoxicity:  0.178 Hek293 Cytotoxicity:  0.118
BCF:   0.583
?
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:   3.127
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.441
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.844
?
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
NPO16999 Paeonia emodi Species Paeoniaceae Eukaryota n.a. root n.a. PMID[12612406]
NPO16333 Chenopodium album Species Chenopodiaceae Eukaryota n.a. n.a. n.a. PMID[15387648]
NPO13602 Lavandula multifida Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[31500359]
NPO13602 Lavandula multifida Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[36676052]
NPO10096 Streptomyces flaveolus Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO14011 Sargassum yezoense Species Sargassaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16999 Paeonia emodi Species Paeoniaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13602 Lavandula multifida Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16333 Chenopodium album Species Chenopodiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16333 Chenopodium album Species Chenopodiaceae Eukaryota Leaf n.a. n.a. Database[FooDB]
NPO16333 Chenopodium album Species Chenopodiaceae Eukaryota Plant n.a. n.a. Database[FooDB]
NPO16333 Chenopodium album Species Chenopodiaceae Eukaryota Seed n.a. n.a. Database[FooDB]
NPO16333 Chenopodium album Species Chenopodiaceae Eukaryota n.a. n.a. Database[FooDB]
NPO16333 Chenopodium album Species Chenopodiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO16999 Paeonia emodi Species Paeoniaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO16333 Chenopodium album Species Chenopodiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO16999 Paeonia emodi Species Paeoniaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO17634 Lycopodium carinatum Species Lycopodiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13602 Lavandula multifida Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14011 Sargassum yezoense Species Sargassaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13345 Dendrobium farmerii Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16999 Paeonia emodi Species Paeoniaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10096 Streptomyces flaveolus Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO16333 Chenopodium album Species Chenopodiaceae 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
NPT422 Protein family Muscarinic acetylcholine receptor Rattus norvegicus Inhibition = 51.0 % PMID[30554957]
NPT422 Protein family Muscarinic acetylcholine receptor Rattus norvegicus Inhibition = 59.0 % PMID[30554957]
NPT7 Individual protein Thioredoxin reductase 1, cytoplasmic Rattus norvegicus Potency n.a. 4744.4 nM PubChem BioAssay data set
NPT7 Individual protein Thioredoxin reductase 1, cytoplasmic Rattus norvegicus Potency n.a. 398.1 nM PubChem BioAssay data set
NPT5 Individual protein Histone-lysine N-methyltransferase, H3 lysine-9 specific 3 Homo sapiens Potency n.a. 11220.2 nM PubChem BioAssay data set
NPT21851 Single protein Dihydroorotate dehydrogenase (fumarate) Leishmania major IC50 = 795300.0 nM PMID[30145372]
NPT21851 Single protein Dihydroorotate dehydrogenase (fumarate) Leishmania major IC50 = 794328.23 nM PMID[30145372]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT28833 No target No relevant target n.a. Retention_index = -0.47 n.a. PMID[36796127]
NPT28833 No target No relevant target n.a. pKa = 7.72 n.a. PMID[36796127]
NPT28833 No target No relevant target n.a. pKa = 7.63 n.a. PMID[36796127]
NPT28833 No target No relevant target n.a. pKa = 5.8 n.a. PMID[36796127]
NPT28833 No target No relevant target n.a. pKa = 7.71 n.a. PMID[36796127]
NPT28833 No target No relevant target n.a. pKa = 7.64 n.a. PMID[36796127]
NPT28438 Unchecked Unchecked n.a. pKa = 16.45 n.a. PMID[36796127]
NPT634 Organism Leishmania amazonensis Leishmania amazonensis IC50 > 100000.0 nM PMID[30145372]
NPT634 Organism Leishmania amazonensis Leishmania amazonensis IC50 > 25000.0 nM PMID[30145372]
NPT1018 Organism Trypanosoma brucei Trypanosoma brucei IC50 > 100000.0 nM PMID[30145372]

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. LogD = -0.89 n.a. PMID[36796127]
n.a. n.a. LogP < 0.0 n.a. PMID[36796127]
n.a. n.a. LogD < 0.0 n.a. PMID[36796127]
n.a. n.a. LogD = -0.1 n.a. PMID[36796127]
n.a. n.a. LogP = 0.7 n.a. PMID[36796127]





 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 NPC245836 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
1.0 High Similarity NPC233910
1.0 High Similarity NPC39830
0.75 Intermediate Similarity NPC213126
0.75 Intermediate Similarity NPC317474
0.75 Intermediate Similarity NPC209773
0.75 Intermediate Similarity NPC609072
0.6792 Remote Similarity NPC69496
0.6792 Remote Similarity NPC161229
0.5273 Remote Similarity NPC84281
0.5273 Remote Similarity NPC169485

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC245836 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
1.0 High Similarity NPD2570 Phase 4
1.0 High Similarity NPD2571 Approved
1.0 High Similarity NPD2572 Clinical (unspecified phase)
1.0 High Similarity NPD2573 Approved
1.0 High Similarity NPD2574 Discontinued
0.9773 High Similarity NPD2566 Approved
0.75 Intermediate Similarity NPD2610 Approved
0.75 Intermediate Similarity NPD2611 Phase 4
0.75 Intermediate Similarity NPD2612 Phase 4
0.6792 Remote Similarity NPD2608 Approved
0.6792 Remote Similarity NPD2609 Approved
0.6792 Remote Similarity NPD2613 Approved
0.6731 Remote Similarity NPD2575 Phase 3
0.5263 Remote Similarity NPD3089 Approved
0.5263 Remote Similarity NPD3090 Approved
0.5179 Remote Similarity NPD3132 Phase 4
0.5172 Remote Similarity NPD3087 Approved
0.5172 Remote Similarity NPD3088 Approved
0.5085 Remote Similarity NPD3615 Approved
0.5085 Remote Similarity NPD3616 Approved

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