Natural Product: NPC605056

Natural Product IDNPC605056
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 MBZKDBQDALOSRP-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL400777
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0002506] Isoflavonoids
        • [CHEMONTID:0004154] Hydroxyisoflavonoids

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 MBZKDBQDALOSRP-UHFFFAOYSA-N
Standard InCHI InChI=1S/C22H20O6/c1-22(2)10-9-14-15(28-22)11-16-18(20(14)26-4)19(23)17(21(24)27-16)12-5-7-13(25-3)8-6-12/h5-11,23H,1-4H3
SMILES COc1ccc(-c2c(O)c3c(OC)c4c(cc3oc2=O)OC(C)(C)C=C4)cc1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   380.13 Volume:   383.856
?
Van der Waals volume.
Dense:   0.99 LogP:   3.742
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.303
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.995
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   23.0
TPSA:   78.13
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   1.0 Rings:   4.0
Heavy Atoms:   6.0

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:   2.824 Fsp3:   0.227
MCE-18:   51.852
?
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:   0.762 Fluc inhibitor:   0.526
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.687
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.861
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.305 Promiscuous compounds:   0.185

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.923 MDCK Permeability:   -4.729
Pgp-inhibitor:   0.105 Pgp-substrate:   0.001
PAMPA:   0.21
?
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):   0.001
20% Bioavailability (F20%):   0.649 30% Bioavailability (F30%):   0.383
50% Bioavailability (F50%):   0.686

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.18 MRP1:   0.984
Plasma Protein Binding (PPB):   97.979% Volume Distribution (VD):   0.083
Fu: 1.703%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.992
OATP1B3 inhibitor:   0.937 BCRP inhibitor:   0.0
BSEP inhibitor:   0.974

ADMET: Metabolism

CYP1A2-inhibitor:   0.023 CYP1A2-substrate:   0.029
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.565
CYP2C9-inhibitor:   0.998 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.393 CYP2D6-substrate:   0.001
CYP3A4-inhibitor:   0.001 CYP3A4-substrate:   0.321
CYP2B6-substrate:   0.001 CYP2C8-inhibitor:   0.998
HLM stability:   0.337
?
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):  3.997 Half-life (T1/2):  0.574

ADMET: Toxicity

hERG Blockers:  0.187 hERG Blockers (10um):  0.455
Human Hepatotoxicity (H-HT):  0.506 Drug-induced Liver Injury (DILI):  0.89
AMES Toxicity:  0.657 Rat Oral Acute Toxicity:  0.507
Maximum Recommended Daily Dose:  0.566 Skin Sensitization:  0.403
Carcinogencity:  0.885 Eye Corrosion:  0.045
Eye Irritation:  0.901 Respiratory Toxicity:  0.832
Drug-induced Neurotoxicity:  0.289 Ototoxicity:  0.238
Hematotoxicity:  0.322 Drug-induced Nephrotoxicity:  0.304
Genotoxicity:  0.301 RPMI-8226 Immunitoxicity:  0.116
A549 Cytotoxicity:  0.09 Hek293 Cytotoxicity:  0.416
BCF:   1.577
?
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:   4.371
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.156
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.342
?
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
NPO27553 Derris scandens Species Fabaceae Eukaryota n.a. stem n.a. DOI[10.1016/S0031-9422(99)00103-X]
NPO27553 Derris scandens Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[19969457]
NPO27553 Derris scandens Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[21314138]
NPO54343 Erythrina indica Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO415 Deguelia hatschbachii Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4761 Derris robusta Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27553 Derris scandens Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27553 Derris scandens Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO4761 Derris robusta Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO27553 Derris scandens Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO4761 Derris robusta Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO415 Deguelia hatschbachii Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27553 Derris scandens Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4761 Derris robusta Species Fabaceae 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
NPT149 Individual protein Endoplasmic reticulum-associated amyloid beta-peptide-binding protein Homo sapiens Potency = 19952.6 nM PubChem BioAssay data set
NPT109 Individual protein Cytochrome P450 3A4 Homo sapiens Potency = 6309.6 nM PubChem BioAssay data set
NPT72 Individual protein Solute carrier organic anion transporter family member 1B3 Homo sapiens Inhibition = 74.37 % PMID[23571415]
NPT73 Individual protein Solute carrier organic anion transporter family member 1B1 Homo sapiens Inhibition = 96.44 % PMID[23571415]
NPT61 Individual protein Beta-glucocerebrosidase Homo sapiens Potency n.a. 1995.3 nM PubChem BioAssay data set
NPT94 Individual protein Aldehyde dehydrogenase 1A1 Homo sapiens Potency = 22387.2 nM PubChem BioAssay data set
NPT48 Individual protein Lysine-specific demethylase 4D-like Homo sapiens Potency = 25118.9 nM PubChem BioAssay data set
NPT46 Individual protein Thyroid hormone receptor beta-1 Homo sapiens Potency = 0.0631 nM PubChem BioAssay data set
NPT51 Individual protein Microtubule-associated protein tau Homo sapiens Potency = 10000.0 nM PubChem BioAssay data set
NPT539 Individual protein Cellular tumor antigen p53 Homo sapiens Potency = 7943.3 nM PubChem BioAssay data set
NPT45 Individual protein Ubiquitin carboxyl-terminal hydrolase 2 Homo sapiens Potency = 10000.0 nM PubChem BioAssay data set
NPT539 Individual protein Cellular tumor antigen p53 Homo sapiens Potency = 6309.6 nM PubChem BioAssay data set

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT28438 Unchecked Unchecked n.a. Activity n.a. n.a. n.a. PMID[18020309]
NPT28438 Unchecked Unchecked n.a. Potency n.a. 7079.5 nM PubChem BioAssay data set
NPT29533 Protein-protein interaction Menin/Histone-lysine N-methyltransferase MLL Homo sapiens Potency = 22387.2 nM PubChem BioAssay data set

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 NPC605056 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
0.85 High Similarity NPC601235
0.6875 Remote Similarity NPC602496
0.5733 Remote Similarity NPC71903
0.5395 Remote Similarity NPC608569
0.5373 Remote Similarity NPC154176
0.5301 Remote Similarity NPC484047
0.519 Remote Similarity NPC229847

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC605056 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