Natural Product: NPC18347

Natural Product IDNPC18347
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Chasmanthin
IUPAC Name n.a.
Synonyms Chasmanthin
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL458613
PubChem CID 442012
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0001640] Naphthopyrans

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 TXOMRNMZLZXJQP-OQDMGONLSA-N
Standard InCHI InChI=1S/C20H22O7/c1-18-7-11(9-4-6-24-8-9)25-16(21)10(18)3-5-19(2)14(18)12-13-15(26-13)20(19,23)17(22)27-12/h4,6,8,10-15,23H,3,5,7H2,1-2H3/t10-,11+,12+,13-,14-,15-,18+,19+,20-/m0/s1
SMILES O=C1O[C@H](C[C@@]2([C@H]1CC[C@@]1([C@H]2[C@@H]2OC(=O)[C@@]1(O)[C@@H]1[C@H]2O1)C)C)c1cocc1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   374.14 Volume:   354.123
?
Van der Waals volume.
Dense:   1.057 LogP:   1.182
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.381
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.044
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   28.0
TPSA:   98.5
?
Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   1.0 Rings:   7.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.59 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   5.848 Fsp3:   0.7
MCE-18:   133.412
?
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:   0.303 Fluc inhibitor:   0.001
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.013
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.002
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.083 Promiscuous compounds:   0.522

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.224 MDCK Permeability:   -4.664
Pgp-inhibitor:   0.632 Pgp-substrate:   0.276
PAMPA:   0.782
?
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):   0.073
20% Bioavailability (F20%):   0.512 30% Bioavailability (F30%):   0.837
50% Bioavailability (F50%):   0.942

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.009 MRP1:   0.887
Plasma Protein Binding (PPB):   83.714% Volume Distribution (VD):   0.285
Fu: 16.363%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.994
OATP1B3 inhibitor:   0.986 BCRP inhibitor:   0.068
BSEP inhibitor:   0.986

ADMET: Metabolism

CYP1A2-inhibitor:   0.001 CYP1A2-substrate:   0.395
CYP2C19-inhibitor:   0.295 CYP2C19-substrate:   0.027
CYP2C9-inhibitor:   0.001 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.148
CYP3A4-inhibitor:   0.99 CYP3A4-substrate:   0.991
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.972
HLM stability:   0.916
?
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):  3.567 Half-life (T1/2):  3.51

ADMET: Toxicity

hERG Blockers:  0.033 hERG Blockers (10um):  0.272
Human Hepatotoxicity (H-HT):  0.607 Drug-induced Liver Injury (DILI):  0.985
AMES Toxicity:  0.922 Rat Oral Acute Toxicity:  0.649
Maximum Recommended Daily Dose:  0.87 Skin Sensitization:  0.991
Carcinogencity:  0.891 Eye Corrosion:  0.022
Eye Irritation:  0.865 Respiratory Toxicity:  0.497
Drug-induced Neurotoxicity:  0.649 Ototoxicity:  0.232
Hematotoxicity:  0.424 Drug-induced Nephrotoxicity:  0.927
Genotoxicity:  0.997 RPMI-8226 Immunitoxicity:  0.176
A549 Cytotoxicity:  0.335 Hek293 Cytotoxicity:  0.147
BCF:   1.177
?
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:   3.757
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.357
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.898
?
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
NPO10715 Fibraurea tinctoria Species Menispermaceae Eukaryota n.a. n.a. n.a. PMID[17994701]
NPO10715 Fibraurea tinctoria Species Menispermaceae Eukaryota n.a. n.a. n.a. PMID[18829331]
NPO19568 Aconitum chrysotrichum Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19929 Jateorhiza palmata Species Menispermaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10715 Fibraurea tinctoria Species Menispermaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19929 Jateorhiza palmata Species Menispermaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO19568 Aconitum chrysotrichum Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO19929 Jateorhiza palmata Species Menispermaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO19568 Aconitum chrysotrichum Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO19929 Jateorhiza palmata Species Menispermaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO19929 Jateorhiza palmata Species Menispermaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10715 Fibraurea tinctoria Species Menispermaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19568 Aconitum chrysotrichum Species Ranunculaceae 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

In vivo activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT32 Organism Mus musculus Mus musculus Activity = 15.39 % PMID[18829331]
NPT32 Organism Mus musculus Mus musculus Activity = 18.46 % PMID[18829331]
NPT32 Organism Mus musculus Mus musculus Activity = 22.41 % PMID[18829331]
NPT32 Organism Mus musculus Mus musculus Activity = 23.99 % PMID[18829331]
NPT32 Organism Mus musculus Mus musculus Activity = 31.6 % PMID[18829331]
NPT32 Organism Mus musculus Mus musculus Activity = 32.49 % PMID[18829331]
NPT32 Organism Mus musculus Mus musculus Activity = 13.15 % PMID[18829331]
NPT32 Organism Mus musculus Mus musculus Activity = 18.75 % PMID[18829331]
NPT32 Organism Mus musculus Mus musculus Activity = 21.76 % PMID[18829331]
NPT32 Organism Mus musculus Mus musculus Activity = 21.23 % PMID[18829331]
NPT32 Organism Mus musculus Mus musculus Activity = 23.73 % PMID[18829331]
NPT32 Organism Mus musculus Mus musculus Activity = 20.71 % PMID[18829331]





 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 NPC18347 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
0.7536 Intermediate Similarity NPC271657
0.6316 Remote Similarity NPC149896
0.6111 Remote Similarity NPC600426
0.5972 Remote Similarity NPC608381
0.5972 Remote Similarity NPC609872
0.55 Remote Similarity NPC610061
0.5467 Remote Similarity NPC476944
0.5467 Remote Similarity NPC601789
0.5417 Remote Similarity NPC476943
0.5385 Remote Similarity NPC475967
0.5325 Remote Similarity NPC262198
0.5325 Remote Similarity NPC485313
0.525 Remote Similarity NPC299038
0.525 Remote Similarity NPC610593
0.5125 Remote Similarity NPC250228
0.5122 Remote Similarity NPC606944
0.5067 Remote Similarity NPC606229

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC18347 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