Natural Product: NPC298223

Natural Product IDNPC298223
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 VOCGSQHKPZSIKB-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 122835
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0000337] Flavans
          • [CHEMONTID:0003646] 6-prenylated flavans
            • [CHEMONTID:0003507] 6-prenylated flavanones

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 VOCGSQHKPZSIKB-UHFFFAOYSA-N
Standard InCHI InChI=1S/C21H22O4/c1-13(2)4-5-15-10-17-18(23)11-20(14-6-8-16(22)9-7-14)25-21(17)12-19(15)24-3/h4,6-10,12,20,22H,5,11H2,1-3H3
SMILES CC(=CCc1cc2C(=O)CC(c3ccc(cc3)O)Oc2cc1OC)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   338.15 Volume:   360.172
?
Van der Waals volume.
Dense:   0.939 LogP:   4.404
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.649
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.012
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   19.0
TPSA:   55.76
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   1.0 Rings:   3.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.827 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.996 Fsp3:   0.286
MCE-18:   56.667
?
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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.872 Fluc inhibitor:   0.377
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.656
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.494
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.323 Promiscuous compounds:   0.02

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.689 MDCK Permeability:   -4.673
Pgp-inhibitor:   0.981 Pgp-substrate:   0.032
PAMPA:   0.341
?
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):   0.007
20% Bioavailability (F20%):   0.096 30% Bioavailability (F30%):   0.95
50% Bioavailability (F50%):   0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.782
Plasma Protein Binding (PPB):   94.657% Volume Distribution (VD):   0.256
Fu: 4.231%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.891
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   1.0
BSEP inhibitor:   0.986

ADMET: Metabolism

CYP1A2-inhibitor:   0.007 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.994 CYP2C19-substrate:   1.0
CYP2C9-inhibitor:   0.125 CYP2C9-substrate:   0.071
CYP2D6-inhibitor:   0.505 CYP2D6-substrate:   0.996
CYP3A4-inhibitor:   0.009 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.999
HLM stability:   1.0
?
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):  7.784 Half-life (T1/2):  1.34

ADMET: Toxicity

hERG Blockers:  0.252 hERG Blockers (10um):  0.618
Human Hepatotoxicity (H-HT):  0.77 Drug-induced Liver Injury (DILI):  0.558
AMES Toxicity:  0.675 Rat Oral Acute Toxicity:  0.722
Maximum Recommended Daily Dose:  0.703 Skin Sensitization:  0.651
Carcinogencity:  0.76 Eye Corrosion:  0.0
Eye Irritation:  0.738 Respiratory Toxicity:  0.635
Drug-induced Neurotoxicity:  0.833 Ototoxicity:  0.577
Hematotoxicity:  0.402 Drug-induced Nephrotoxicity:  0.773
Genotoxicity:  0.879 RPMI-8226 Immunitoxicity:  0.078
A549 Cytotoxicity:  0.352 Hek293 Cytotoxicity:  0.717
BCF:   1.737
?
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:   4.632
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.944
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.444
?
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
NPO30150 Psoralea corylifolia Species Fabaceae Eukaryota seeds n.a. n.a. PMID[18359631]
NPO28809 Cullen corylifolium Species Fabaceae Eukaryota n.a. fruit n.a. PMID[20663508]
NPO28809 Cullen corylifolium Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[24507928]
NPO30150 Psoralea corylifolia Species Fabaceae Eukaryota Fruits n.a. n.a. PMID[25710081]
NPO30150 Psoralea corylifolia Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[3069958]
NPO30150 Psoralea corylifolia Species Fabaceae Eukaryota n.a. seed n.a. PMID[8759164]
NPO28809 Cullen corylifolium Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[9544566]
NPO28809 Cullen corylifolium Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO30150 Psoralea corylifolia Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO30150 Psoralea corylifolia Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO28809 Cullen corylifolium Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO30150 Psoralea corylifolia Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO28809 Cullen corylifolium Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO28809 Cullen corylifolium Species Fabaceae 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
NPT204 Individual protein Acetylcholinesterase Homo sapiens Inhibition = 80.0 % PMID[33984802]
NPT740 Individual protein Beta-secretase 1 Homo sapiens Inhibition = 20.0 % PMID[33984802]

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 NPC298223 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 NPC169591
1.0 High Similarity NPC604412
0.7368 Intermediate Similarity NPC39329
0.7368 Intermediate Similarity NPC51032
0.6949 Remote Similarity NPC69674
0.6833 Remote Similarity NPC68104
0.678 Remote Similarity NPC472580
0.6393 Remote Similarity NPC221432
0.6393 Remote Similarity NPC257097
0.6393 Remote Similarity NPC75049
0.6333 Remote Similarity NPC143896
0.6333 Remote Similarity NPC164980
0.6316 Remote Similarity NPC210084
0.629 Remote Similarity NPC220998
0.619 Remote Similarity NPC76338
0.619 Remote Similarity NPC250242
0.6154 Remote Similarity NPC291508
0.6 Remote Similarity NPC209040
0.5818 Remote Similarity NPC329225
0.5818 Remote Similarity NPC147686
0.5714 Remote Similarity NPC107572
0.5714 Remote Similarity NPC32739
0.5625 Remote Similarity NPC149026
0.5625 Remote Similarity NPC265040
0.5614 Remote Similarity NPC225153
0.5614 Remote Similarity NPC479876
0.5593 Remote Similarity NPC329203
0.5593 Remote Similarity NPC222342
0.5556 Remote Similarity NPC110303
0.5556 Remote Similarity NPC601247
0.5538 Remote Similarity NPC17170
0.5538 Remote Similarity NPC109223
0.5538 Remote Similarity NPC310130
0.5538 Remote Similarity NPC10937
0.55 Remote Similarity NPC475267
0.5469 Remote Similarity NPC150408
0.5455 Remote Similarity NPC486094
0.5362 Remote Similarity NPC36275
0.5303 Remote Similarity NPC197252
0.5294 Remote Similarity NPC161506
0.5278 Remote Similarity NPC479215
0.5246 Remote Similarity NPC469764
0.5246 Remote Similarity NPC606248
0.5231 Remote Similarity NPC236766
0.5224 Remote Similarity NPC125855
0.5217 Remote Similarity NPC473078
0.5211 Remote Similarity NPC228504
0.5167 Remote Similarity NPC1612
0.5167 Remote Similarity NPC183959
0.5143 Remote Similarity NPC35038
0.5085 Remote Similarity NPC476480
0.5085 Remote Similarity NPC84585
0.5082 Remote Similarity NPC300668
0.5077 Remote Similarity NPC258630
0.507 Remote Similarity NPC246948
0.507 Remote Similarity NPC142405
0.507 Remote Similarity NPC39752
0.5068 Remote Similarity NPC472636

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC298223 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
0.5818 Remote Similarity NPD1549 Phase 2

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