Natural Product: NPC38099

Natural Product IDNPC38099
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Murpanicin
IUPAC Name 8-(1-ethoxy-2-hydroxy-3-methylbut-3-enyl)-7-methoxychromen-2-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL3426682
PubChem CID 188750
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 GDLSTIJVZWVVPB-UHFFFAOYSA-N
Standard InCHI InChI=1S/C17H20O5/c1-5-21-17(15(19)10(2)3)14-12(20-4)8-6-11-7-9-13(18)22-16(11)14/h6-9,15,17,19H,2,5H2,1,3-4H3
SMILES CCOC(c1c(OC)ccc2c1oc(=O)cc2)C(C(=C)C)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   304.13 Volume:   313.608
?
Van der Waals volume.
Dense:   0.97 LogP:   2.252
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.253
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.541
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   13.0
TPSA:   68.9
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   1.0 Rings:   2.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.656 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.62 Fsp3:   0.353
MCE-18:   28.0
?
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:   0.172 Fluc inhibitor:   0.001
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.988
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.444
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.119 Promiscuous compounds:   0.006

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.749 MDCK Permeability:   -4.58
Pgp-inhibitor:   0.0 Pgp-substrate:   0.0
PAMPA:   0.439
?
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):   0.005
20% Bioavailability (F20%):   0.683 30% Bioavailability (F30%):   0.829
50% Bioavailability (F50%):   0.813

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.001 MRP1:   0.995
Plasma Protein Binding (PPB):   86.111% Volume Distribution (VD):   0.132
Fu: 11.423%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.998
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.0
BSEP inhibitor:   0.958

ADMET: Metabolism

CYP1A2-inhibitor:   0.007 CYP1A2-substrate:   0.935
CYP2C19-inhibitor:   0.594 CYP2C19-substrate:   0.191
CYP2C9-inhibitor:   0.768 CYP2C9-substrate:   0.001
CYP2D6-inhibitor:   0.008 CYP2D6-substrate:   0.481
CYP3A4-inhibitor:   0.66 CYP3A4-substrate:   0.656
CYP2B6-substrate:   0.863 CYP2C8-inhibitor:   0.658
HLM stability:   0.926
?
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):  9.35 Half-life (T1/2):  0.82

ADMET: Toxicity

hERG Blockers:  0.072 hERG Blockers (10um):  0.324
Human Hepatotoxicity (H-HT):  0.351 Drug-induced Liver Injury (DILI):  0.557
AMES Toxicity:  0.479 Rat Oral Acute Toxicity:  0.352
Maximum Recommended Daily Dose:  0.733 Skin Sensitization:  0.063
Carcinogencity:  0.722 Eye Corrosion:  0.161
Eye Irritation:  0.959 Respiratory Toxicity:  0.582
Drug-induced Neurotoxicity:  0.469 Ototoxicity:  0.357
Hematotoxicity:  0.186 Drug-induced Nephrotoxicity:  0.212
Genotoxicity:  0.703 RPMI-8226 Immunitoxicity:  0.067
A549 Cytotoxicity:  0.022 Hek293 Cytotoxicity:  0.189
BCF:   1.274
?
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:   3.816
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.356
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.793
?
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. 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]
NPO2715.2 Murraya paniculata (l.) jack var. exotica (l.) huang Varieties 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]
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]
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]
NPO2715.2 Murraya paniculata (l.) jack var. exotica (l.) huang Varieties Rutaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
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

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 = 43300.0 nM PMID[25621853]

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 NPC38099 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 NPC26954
0.7667 Intermediate Similarity NPC484113
0.6441 Remote Similarity NPC199204
0.6393 Remote Similarity NPC153818
0.6393 Remote Similarity NPC232246
0.6379 Remote Similarity NPC50896
0.6379 Remote Similarity NPC326600
0.5672 Remote Similarity NPC287286
0.5652 Remote Similarity NPC312881
0.5574 Remote Similarity NPC610664
0.5484 Remote Similarity NPC62366
0.5373 Remote Similarity NPC479309
0.5352 Remote Similarity NPC484110
0.5323 Remote Similarity NPC229916
0.5323 Remote Similarity NPC122259
0.5294 Remote Similarity NPC469675
0.5294 Remote Similarity NPC479311
0.5246 Remote Similarity NPC175159
0.5238 Remote Similarity NPC188380
0.5238 Remote Similarity NPC224543
0.5238 Remote Similarity NPC185066
0.5231 Remote Similarity NPC168710
0.5231 Remote Similarity NPC605506
0.5161 Remote Similarity NPC80170
0.5161 Remote Similarity NPC96286
0.5152 Remote Similarity NPC479313
0.5143 Remote Similarity NPC129572
0.5143 Remote Similarity NPC479310
0.5079 Remote Similarity NPC225106
0.5079 Remote Similarity NPC184861
0.5079 Remote Similarity NPC281014
0.5079 Remote Similarity NPC212124
0.5079 Remote Similarity NPC294456
0.5077 Remote Similarity NPC31849
0.5077 Remote Similarity NPC85085
0.5075 Remote Similarity NPC167111
0.5075 Remote Similarity NPC318400
0.507 Remote Similarity NPC479308
0.5067 Remote Similarity NPC471764

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC38099 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