Natural Product: NPC605420

Natural Product IDNPC605420
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 GAQSUFOBIREXHT-VQIMIIECSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1807664
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 GAQSUFOBIREXHT-VQIMIIECSA-N
Standard InCHI InChI=1S/C19H18O8/c1-23-9-4-11(20)17-15(5-9)27-16-8-26-12-7-14(25-3)13(24-2)6-10(12)19(16,22)18(17)21/h4-7,16,20,22H,8H2,1-3H3/t16-,19-/m1/s1
SMILES COc1cc(O)c2c(c1)O[C@@H]1COc3cc(OC)c(OC)cc3[C@]1(O)C2=O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   374.1 Volume:   354.821
?
Van der Waals volume.
Dense:   1.054 LogP:   1.664
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.068
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.505
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   22.0
TPSA:   103.68
?
Topological Polar Surface Area.
 H-Bond Acceptor:   8.0
H-Bond Donor:   2.0 Rings:   4.0
Heavy Atoms:   8.0

MedChem Properties

QED Drug-Likeness Score:   0.836 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.507 Fsp3:   0.316
MCE-18:   81.0
?
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:   0.117 Fluc inhibitor:   0.309
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.449
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.212
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.223 Promiscuous compounds:   0.282

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.139 MDCK Permeability:   -4.739
Pgp-inhibitor:   0.036 Pgp-substrate:   0.048
PAMPA:   0.057
?
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):   0.171
20% Bioavailability (F20%):   0.611 30% Bioavailability (F30%):   0.364
50% Bioavailability (F50%):   0.986

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.011 MRP1:   0.814
Plasma Protein Binding (PPB):   79.561% Volume Distribution (VD):   0.007
Fu: 15.962%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.998
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   0.557
BSEP inhibitor:   0.781

ADMET: Metabolism

CYP1A2-inhibitor:   0.956 CYP1A2-substrate:   0.976
CYP2C19-inhibitor:   0.101 CYP2C19-substrate:   0.019
CYP2C9-inhibitor:   0.821 CYP2C9-substrate:   0.001
CYP2D6-inhibitor:   0.398 CYP2D6-substrate:   0.577
CYP3A4-inhibitor:   0.015 CYP3A4-substrate:   0.009
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.127
HLM stability:   0.677
?
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):  8.121 Half-life (T1/2):  2.449

ADMET: Toxicity

hERG Blockers:  0.085 hERG Blockers (10um):  0.422
Human Hepatotoxicity (H-HT):  0.738 Drug-induced Liver Injury (DILI):  0.779
AMES Toxicity:  0.722 Rat Oral Acute Toxicity:  0.482
Maximum Recommended Daily Dose:  0.517 Skin Sensitization:  0.894
Carcinogencity:  0.737 Eye Corrosion:  0.003
Eye Irritation:  0.839 Respiratory Toxicity:  0.852
Drug-induced Neurotoxicity:  0.372 Ototoxicity:  0.501
Hematotoxicity:  0.508 Drug-induced Nephrotoxicity:  0.813
Genotoxicity:  0.487 RPMI-8226 Immunitoxicity:  0.219
A549 Cytotoxicity:  0.444 Hek293 Cytotoxicity:  0.515
BCF:   1.278
?
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:   3.572
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.986
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.051
?
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
NPO24609 Millettia brandisiana Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[18039011]
NPO24609 Millettia brandisiana Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[19124248]
NPO24609 Millettia brandisiana Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO56966 Clitoria fairchildiana Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15841 Clitoria macrophylla Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15841 Clitoria macrophylla Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24609 Millettia brandisiana 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
NPT1044 Individual protein DNA topoisomerase II alpha Homo sapiens Inhibition = 72.1 % PMID[21741833]
NPT28792 Nucleic-acid Nucleic Acid n.a. Tm = 57.3 degrees C PMID[21741833]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT845 Cell line BT-474 Homo sapiens IC50 > 100000.0 nM PMID[21741833]
NPT639 Cell line NCI-H187 Homo sapiens IC50 = 3120.0 nM PMID[21741833]
NPT91 Cell line KB Homo sapiens IC50 = 13280.0 nM PMID[21741833]
NPT83 Cell line MCF7 Homo sapiens IC50 = 23650.0 nM PMID[21741833]
NPT323 Cell line SW-620 Homo sapiens IC50 > 100000.0 nM PMID[21741833]
NPT65 Cell line HepG2 Homo sapiens IC50 > 100000.0 nM PMID[21741833]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 > 100000.0 nM PMID[21741833]

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 NPC605420 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
0.6897 Remote Similarity NPC607486
0.6721 Remote Similarity NPC234052
0.6613 Remote Similarity NPC173137
0.6143 Remote Similarity NPC177480
0.6129 Remote Similarity NPC611309
0.6056 Remote Similarity NPC326877
0.5846 Remote Similarity NPC603764
0.5781 Remote Similarity NPC224280
0.5556 Remote Similarity NPC8636
0.5538 Remote Similarity NPC203080
0.5429 Remote Similarity NPC242395
0.5352 Remote Similarity NPC152477
0.5278 Remote Similarity NPC121333
0.5211 Remote Similarity NPC609259
0.5205 Remote Similarity NPC74559
0.5072 Remote Similarity NPC606577

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC605420 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