Natural Product: NPC21990

Natural Product IDNPC21990
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 RSTDNUBRTQLVBF-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 642896
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000253] Stilbenes

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 RSTDNUBRTQLVBF-UHFFFAOYSA-N
Standard InCHI InChI=1S/C16H18O4/c1-19-14-9-11(8-13(17)10-14)6-7-12-4-3-5-15(18)16(12)20-2/h3-5,8-10,17-18H,6-7H2,1-2H3
SMILES COc1cc(CCc2cccc(c2OC)O)cc(c1)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   274.12 Volume:   287.521
?
Van der Waals volume.
Dense:   0.953 LogP:   3.257
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.16
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.631
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   12.0
TPSA:   58.92
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   2.0 Rings:   2.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.88 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.158 Fsp3:   0.25
MCE-18:   12.0
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Accepted GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   1 PAINS Alert:   0
Colloidal aggregators:   0.327 Fluc inhibitor:   0.154
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.05
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.346
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.674 Promiscuous compounds:   0.252

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.877 MDCK Permeability:   -4.78
Pgp-inhibitor:   0.805 Pgp-substrate:   0.028
PAMPA:   0.025
?
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):   0.037
20% Bioavailability (F20%):   0.909 30% Bioavailability (F30%):   0.802
50% Bioavailability (F50%):   0.983

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.093 MRP1:   0.206
Plasma Protein Binding (PPB):   93.944% Volume Distribution (VD):   -0.593
Fu: 6.546%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.989
OATP1B3 inhibitor:   0.988 BCRP inhibitor:   0.446
BSEP inhibitor:   0.938

ADMET: Metabolism

CYP1A2-inhibitor:   0.997 CYP1A2-substrate:   0.998
CYP2C19-inhibitor:   0.938 CYP2C19-substrate:   0.961
CYP2C9-inhibitor:   1.0 CYP2C9-substrate:   0.996
CYP2D6-inhibitor:   0.916 CYP2D6-substrate:   0.997
CYP3A4-inhibitor:   0.135 CYP3A4-substrate:   0.999
CYP2B6-substrate:   0.181 CYP2C8-inhibitor:   1.0
HLM stability:   0.855
?
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):  8.432 Half-life (T1/2):  1.001

ADMET: Toxicity

hERG Blockers:  0.377 hERG Blockers (10um):  0.777
Human Hepatotoxicity (H-HT):  0.543 Drug-induced Liver Injury (DILI):  0.112
AMES Toxicity:  0.546 Rat Oral Acute Toxicity:  0.174
Maximum Recommended Daily Dose:  0.579 Skin Sensitization:  0.796
Carcinogencity:  0.403 Eye Corrosion:  0.3
Eye Irritation:  0.952 Respiratory Toxicity:  0.745
Drug-induced Neurotoxicity:  0.352 Ototoxicity:  0.347
Hematotoxicity:  0.21 Drug-induced Nephrotoxicity:  0.344
Genotoxicity:  0.275 RPMI-8226 Immunitoxicity:  0.092
A549 Cytotoxicity:  0.385 Hek293 Cytotoxicity:  0.638
BCF:   1.606
?
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:   4.087
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.215
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.739
?
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
NPO30254 Stemona collinsae Species Stemonaceae Eukaryota Leaves, rhizomes, and roots southeast Thailand near Chonburi 2000-Feb, 2001-Jan PMID[12088422]
NPO19620 Stemona tuberosa Species Stemonaceae Eukaryota n.a. n.a. n.a. PMID[15679323]
NPO30254 Stemona collinsae Species Stemonaceae Eukaryota slowly dried tubers Bangkok, Thailand n.a. PMID[15679323]
NPO30254 Stemona collinsae Species Stemonaceae Eukaryota n.a. Southeast Thailand near Chonburi, Khao Khieo, close to the Chanthathen waterfall and Sri Racha n.a. PMID[15679323]
NPO30254 Stemona collinsae Species Stemonaceae Eukaryota n.a. n.a. n.a. PMID[15679323]
NPO19620 Stemona tuberosa Species Stemonaceae Eukaryota roots n.a. n.a. PMID[16643052]
NPO19620 Stemona tuberosa Species Stemonaceae Eukaryota Roots; Stems; Tubers n.a. n.a. PMID[16872143]
NPO19620 Stemona tuberosa Species Stemonaceae Eukaryota roots n.a. n.a. PMID[18452334]
NPO19780 Stemona sessilifolia Species Stemonaceae Eukaryota n.a. root n.a. PMID[21902195]
NPO19620 Stemona tuberosa Species Stemonaceae Eukaryota n.a. rhizome n.a. PMID[21902195]
NPO19620 Stemona tuberosa Species Stemonaceae Eukaryota n.a. tuberous root n.a. PMID[21902195]
NPO19620 Stemona tuberosa Species Stemonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19780 Stemona sessilifolia Species Stemonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12104 Stemona cf. pierrei Species Stemonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO30254 Stemona collinsae Species Stemonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12104 Stemona cf. pierrei Species Stemonaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO19620 Stemona tuberosa Species Stemonaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO19780 Stemona sessilifolia Species Stemonaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO19780 Stemona sessilifolia Species Stemonaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO19620 Stemona tuberosa Species Stemonaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO12104 Stemona cf. pierrei Species Stemonaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO19780 Stemona sessilifolia Species Stemonaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO19620 Stemona tuberosa Species Stemonaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO30254 Stemona collinsae Species Stemonaceae Eukaryota leaf and root n.a. n.a. Database[Title]
NPO19620 Stemona tuberosa Species Stemonaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19780 Stemona sessilifolia Species Stemonaceae 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





 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 NPC21990 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
0.7273 Intermediate Similarity NPC121115
0.6818 Remote Similarity NPC22610
0.6809 Remote Similarity NPC33270
0.6667 Remote Similarity NPC126836
0.6591 Remote Similarity NPC276737
0.6591 Remote Similarity NPC141090
0.6531 Remote Similarity NPC236760
0.6383 Remote Similarity NPC117214
0.6304 Remote Similarity NPC53906
0.625 Remote Similarity NPC150624
0.617 Remote Similarity NPC116907
0.6042 Remote Similarity NPC28765
0.5833 Remote Similarity NPC282496
0.5385 Remote Similarity NPC95168
0.5283 Remote Similarity NPC63574

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC21990 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