Natural Product: NPC602291

Natural Product IDNPC602291
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 CMRBCUQYNLDSKE-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL357089
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 CMRBCUQYNLDSKE-UHFFFAOYSA-N
Standard InCHI InChI=1S/C21H22O8/c1-23-12-9-13(24-2)17-14(10-12)29-19(21(28-6)18(17)22)11-7-15(25-3)20(27-5)16(8-11)26-4/h7-10H,1-6H3
SMILES COc1cc(OC)c2c(=O)c(OC)c(-c3cc(OC)c(OC)c(OC)c3)oc2c1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   402.13 Volume:   395.333
?
Van der Waals volume.
Dense:   1.017 LogP:   2.274
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.646
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.725
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   7.0 Rigid Bonds:   18.0
TPSA:   85.59
?
Topological Polar Surface Area.
 H-Bond Acceptor:   8.0
H-Bond Donor:   0.0 Rings:   3.0
Heavy Atoms:   8.0

MedChem Properties

QED Drug-Likeness Score:   0.594 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.357 Fsp3:   0.286
MCE-18:   20.0
?
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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.029 Fluc inhibitor:   0.273
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.839
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.664
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.381 Promiscuous compounds:   0.36

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.479 MDCK Permeability:   -4.52
Pgp-inhibitor:   0.997 Pgp-substrate:   0.035
PAMPA:   0.007
?
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):   0.03
20% Bioavailability (F20%):   0.004 30% Bioavailability (F30%):   0.011
50% Bioavailability (F50%):   0.938

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.043 MRP1:   0.783
Plasma Protein Binding (PPB):   91.243% Volume Distribution (VD):   -0.081
Fu: 7.926%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.145
OATP1B3 inhibitor:   0.982 BCRP inhibitor:   0.955
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.814
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.663
CYP2C9-inhibitor:   0.992 CYP2C9-substrate:   0.006
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   1.0
CYP3A4-inhibitor:   0.423 CYP3A4-substrate:   0.001
CYP2B6-substrate:   0.189 CYP2C8-inhibitor:   0.314
HLM stability:   0.629
?
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):  5.675 Half-life (T1/2):  1.062

ADMET: Toxicity

hERG Blockers:  0.127 hERG Blockers (10um):  0.52
Human Hepatotoxicity (H-HT):  0.491 Drug-induced Liver Injury (DILI):  0.712
AMES Toxicity:  0.393 Rat Oral Acute Toxicity:  0.395
Maximum Recommended Daily Dose:  0.5 Skin Sensitization:  0.376
Carcinogencity:  0.834 Eye Corrosion:  0.443
Eye Irritation:  0.911 Respiratory Toxicity:  0.61
Drug-induced Neurotoxicity:  0.586 Ototoxicity:  0.235
Hematotoxicity:  0.509 Drug-induced Nephrotoxicity:  0.281
Genotoxicity:  0.229 RPMI-8226 Immunitoxicity:  0.137
A549 Cytotoxicity:  0.126 Hek293 Cytotoxicity:  0.337
BCF:   1.809
?
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:   3.675
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.612
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.992
?
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
NPO2715 Murraya paniculata Species Rutaceae Eukaryota n.a. leaf n.a. PMID[24354205]
NPO2715 Murraya paniculata Species Rutaceae Eukaryota n.a. twig n.a. PMID[24354205]
NPO2715 Murraya paniculata Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[34964904]
NPO2715 Murraya paniculata Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[36529712]
NPO2715 Murraya paniculata Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO46928 Ficus altissima Species Moraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2715 Murraya paniculata Species Rutaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO2715 Murraya paniculata Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO2715 Murraya paniculata Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO2715 Murraya paniculata Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO2715 Murraya paniculata Species Rutaceae 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
NPT1315 Individual protein Adenosine A1 receptor Rattus norvegicus Displacement < 10.0 % PMID[8576921]
NPT1316 Individual protein Adenosine A2a receptor Rattus norvegicus Ki n.a. n.a. nM PMID[8576921]
NPT218 Individual protein Adenosine A3 receptor Homo sapiens pKi(uM) = -0.82 n.a. PMID[9438021]
NPT1315 Individual protein Adenosine A1 receptor Rattus norvegicus pKi(uM) n.a. n.a. n.a. PMID[9438021]
NPT1316 Individual protein Adenosine A2a receptor Rattus norvegicus pKi(uM) n.a. n.a. n.a. PMID[9438021]
NPT218 Individual protein Adenosine A3 receptor Homo sapiens Ki = 16200.0 nM PMID[8576921]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference

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 NPC602291 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
0.7755 Intermediate Similarity NPC310259
0.7292 Intermediate Similarity NPC61546
0.7292 Intermediate Similarity NPC72452
0.7083 Intermediate Similarity NPC181250
0.7037 Intermediate Similarity NPC608137
0.7 Intermediate Similarity NPC29536
0.6731 Remote Similarity NPC90582
0.6545 Remote Similarity NPC179126
0.6364 Remote Similarity NPC605582
0.6316 Remote Similarity NPC474170
0.6316 Remote Similarity NPC474388
0.6296 Remote Similarity NPC76376
0.6207 Remote Similarity NPC472535
0.5926 Remote Similarity NPC607530
0.5893 Remote Similarity NPC605569
0.5714 Remote Similarity NPC70853
0.5636 Remote Similarity NPC472438
0.5636 Remote Similarity NPC259058
0.5593 Remote Similarity NPC177839
0.5593 Remote Similarity NPC284353
0.5556 Remote Similarity NPC69752
0.5439 Remote Similarity NPC610359
0.5424 Remote Similarity NPC261548
0.5357 Remote Similarity NPC7973
0.5273 Remote Similarity NPC101294
0.5273 Remote Similarity NPC278556
0.5263 Remote Similarity NPC474037
0.5263 Remote Similarity NPC299923
0.5172 Remote Similarity NPC276905
0.5167 Remote Similarity NPC104459
0.5091 Remote Similarity NPC302408
0.5085 Remote Similarity NPC9966
0.5082 Remote Similarity NPC34725
0.5082 Remote Similarity NPC131557

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC602291 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