Natural Product: NPC175159

Natural Product IDNPC175159
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Murralongin
IUPAC Name 2-(7-methoxy-2-oxochromen-8-yl)-3-methylbut-2-enal
Synonyms Murralongin
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1098016
PubChem CID 179620
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000145] Coumarins 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 PBAZKMWQUBDDLZ-UHFFFAOYSA-N
Standard InCHI InChI=1S/C15H14O4/c1-9(2)11(8-16)14-12(18-3)6-4-10-5-7-13(17)19-15(10)14/h4-8H,1-3H3
SMILES O=CC(=C(C)C)c1c(OC)ccc2c1oc(=O)cc2

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   258.09 Volume:   267.589
?
Van der Waals volume.
Dense:   0.965 LogP:   2.05
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.982
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.276
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   14.0
TPSA:   56.51
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   0.0 Rings:   2.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.482 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.811 Fsp3:   0.2
MCE-18:   13.0
?
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:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.342 Fluc inhibitor:   0.018
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.949
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.744
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.568 Promiscuous compounds:   0.113

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.61 MDCK Permeability:   -4.499
Pgp-inhibitor:   0.031 Pgp-substrate:   0.0
PAMPA:   0.175
?
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):   0.003
20% Bioavailability (F20%):   0.474 30% Bioavailability (F30%):   0.255
50% Bioavailability (F50%):   0.267

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.005 MRP1:   0.994
Plasma Protein Binding (PPB):   91.689% Volume Distribution (VD):   -0.06
Fu: 7.197%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.996
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.0
BSEP inhibitor:   0.996

ADMET: Metabolism

CYP1A2-inhibitor:   0.003 CYP1A2-substrate:   0.755
CYP2C19-inhibitor:   0.124 CYP2C19-substrate:   0.014
CYP2C9-inhibitor:   0.528 CYP2C9-substrate:   0.001
CYP2D6-inhibitor:   0.005 CYP2D6-substrate:   0.052
CYP3A4-inhibitor:   0.237 CYP3A4-substrate:   0.821
CYP2B6-substrate:   0.31 CYP2C8-inhibitor:   0.415
HLM stability:   0.948
?
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):  7.729 Half-life (T1/2):  0.544

ADMET: Toxicity

hERG Blockers:  0.079 hERG Blockers (10um):  0.279
Human Hepatotoxicity (H-HT):  0.562 Drug-induced Liver Injury (DILI):  0.92
AMES Toxicity:  0.713 Rat Oral Acute Toxicity:  0.474
Maximum Recommended Daily Dose:  0.703 Skin Sensitization:  0.393
Carcinogencity:  0.863 Eye Corrosion:  0.492
Eye Irritation:  0.966 Respiratory Toxicity:  0.697
Drug-induced Neurotoxicity:  0.33 Ototoxicity:  0.135
Hematotoxicity:  0.433 Drug-induced Nephrotoxicity:  0.338
Genotoxicity:  0.97 RPMI-8226 Immunitoxicity:  0.115
A549 Cytotoxicity:  0.057 Hek293 Cytotoxicity:  0.271
BCF:   1.263
?
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:   4.246
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.239
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.0
?
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
NPO5744 Galipea panamensis Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[20423106]
NPO2715 Murraya paniculata Species Rutaceae Eukaryota n.a. twig n.a. PMID[24354205]
NPO2715 Murraya paniculata Species Rutaceae Eukaryota n.a. leaf n.a. PMID[24354205]
NPO33003 murraya alata Species Rutaceae Eukaryota leaves n.a. n.a. PMID[25621853]
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]
NPO1383.1 Murraya paniculata var. omphalocarpa Varieties Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5744 Galipea panamensis Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24771 Boenninghausenia albiflora Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2715.1 Murraya paniculata var. exotica Varieties Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO33003 murraya alata Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2715 Murraya paniculata Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24771 Boenninghausenia albiflora Species Rutaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO2715.1 Murraya paniculata var. exotica Varieties Rutaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO2715 Murraya paniculata Species Rutaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO1383.1 Murraya paniculata var. omphalocarpa Varieties Rutaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO2715 Murraya paniculata Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO2715.1 Murraya paniculata var. exotica Varieties Rutaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO24771 Boenninghausenia albiflora 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]
NPO24771 Boenninghausenia albiflora 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]
NPO5744 Galipea panamensis Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2715 Murraya paniculata Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1383.1 Murraya paniculata var. omphalocarpa Varieties Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24771 Boenninghausenia albiflora 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
NPT3101 Individual protein Carbonic anhydrase XIII Homo sapiens Ki = 8890.0 nM PMID[22892213]
NPT233 Individual protein Carbonic anhydrase II Homo sapiens Ki > 100000.0 nM PMID[22892213]
NPT955 Individual protein Carbonic anhydrase VII Homo sapiens Ki = 8850.0 nM PMID[22892213]
NPT948 Individual protein Carbonic anhydrase IX Homo sapiens Ki = 8120.0 nM PMID[22892213]
NPT949 Individual protein Carbonic anhydrase XII Homo sapiens Ki = 7440.0 nM PMID[22892213]
NPT947 Individual protein Carbonic anhydrase I Homo sapiens Ki = 9110.0 nM PMID[22892213]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT113 Cell line RAW264.7 Mus musculus IC50 = 12400.0 nM PMID[25621853]
NPT466 Cell line U-937 Homo sapiens CC50 = 121.4 ug.mL-1 PMID[20423106]
NPT3632 Organism Leishmania panamensis Leishmania panamensis EC50 > 100.0 ug.mL-1 PMID[20423106]

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 NPC175159 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
0.7551 Intermediate Similarity NPC610664
0.6667 Remote Similarity NPC605506
0.6226 Remote Similarity NPC50896
0.6226 Remote Similarity NPC326600
0.6038 Remote Similarity NPC96286
0.5926 Remote Similarity NPC229916
0.5926 Remote Similarity NPC122259
0.5873 Remote Similarity NPC484110
0.5789 Remote Similarity NPC168710
0.5741 Remote Similarity NPC80170
0.5741 Remote Similarity NPC55147
0.5741 Remote Similarity NPC472516
0.5741 Remote Similarity NPC271600
0.5714 Remote Similarity NPC199204
0.5536 Remote Similarity NPC62366
0.5536 Remote Similarity NPC185066
0.5357 Remote Similarity NPC225106
0.5357 Remote Similarity NPC184861
0.5357 Remote Similarity NPC281014
0.5357 Remote Similarity NPC212124
0.5357 Remote Similarity NPC294456
0.5323 Remote Similarity NPC484112
0.5246 Remote Similarity NPC26954
0.5246 Remote Similarity NPC38099
0.5156 Remote Similarity NPC129572
0.5088 Remote Similarity NPC13007
0.5088 Remote Similarity NPC104796

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC175159 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