Natural Product: NPC250214

Natural Product IDNPC250214
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Agrandol
IUPAC Name (2S)-5,7-dihydroxy-6-methoxy-8-(3-methylbut-2-enyl)-2-phenyl-2,3-dihydrochromen-4-one
Synonyms Agrandol
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL491588
PubChem CID 15895373
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0000337] Flavans
          • [CHEMONTID:0003642] 8-prenylated flavans
            • [CHEMONTID:0003508] 8-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 DPWCTCFTFSFYCZ-INIZCTEOSA-N
Standard InCHI InChI=1S/C21H22O5/c1-12(2)9-10-14-18(23)21(25-3)19(24)17-15(22)11-16(26-20(14)17)13-7-5-4-6-8-13/h4-9,16,23-24H,10-11H2,1-3H3/t16-/m0/s1
SMILES CC(=CCc1c(c(c(c2C(=O)C[C@@H](c3ccccc3)Oc12)O)OC)O)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   354.15 Volume:   368.962
?
Van der Waals volume.
Dense:   0.96 LogP:   4.537
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.666
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.312
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   19.0
TPSA:   75.99
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   2.0 Rings:   3.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.8 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.193 Fsp3:   0.286
MCE-18:   59.815
?
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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   1
Chelating Alert:   1 PAINS Alert:   0
Colloidal aggregators:   0.828 Fluc inhibitor:   0.616
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.54
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.487
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.282 Promiscuous compounds:   0.033

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.01 MDCK Permeability:   -4.734
Pgp-inhibitor:   0.999 Pgp-substrate:   0.012
PAMPA:   0.238
?
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):   0.013
20% Bioavailability (F20%):   0.097 30% Bioavailability (F30%):   0.989
50% Bioavailability (F50%):   0.998

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.021 MRP1:   0.959
Plasma Protein Binding (PPB):   97.894% Volume Distribution (VD):   -0.019
Fu: 1.914%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   0.991
BSEP inhibitor:   0.929

ADMET: Metabolism

CYP1A2-inhibitor:   0.034 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.864 CYP2C19-substrate:   0.999
CYP2C9-inhibitor:   0.083 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.004 CYP2D6-substrate:   0.439
CYP3A4-inhibitor:   0.991 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
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):  3.133 Half-life (T1/2):  1.144

ADMET: Toxicity

hERG Blockers:  0.073 hERG Blockers (10um):  0.492
Human Hepatotoxicity (H-HT):  0.776 Drug-induced Liver Injury (DILI):  0.329
AMES Toxicity:  0.695 Rat Oral Acute Toxicity:  0.747
Maximum Recommended Daily Dose:  0.539 Skin Sensitization:  0.935
Carcinogencity:  0.398 Eye Corrosion:  0.001
Eye Irritation:  0.937 Respiratory Toxicity:  0.252
Drug-induced Neurotoxicity:  0.923 Ototoxicity:  0.436
Hematotoxicity:  0.325 Drug-induced Nephrotoxicity:  0.894
Genotoxicity:  0.907 RPMI-8226 Immunitoxicity:  0.096
A549 Cytotoxicity:  0.329 Hek293 Cytotoxicity:  0.432
BCF:   1.898
?
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:   4.696
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.287
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.758
?
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
NPO32494 cedrelopsis microfoliata Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[12350164]
NPO8054 Chara globularis Species Characeae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4142 Ageratina glabrata Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8967 Phellodendron sachalinense Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5876 Dioclea grandiflora Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8886 Protea mellifera Species Proteaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO8886 Protea mellifera Species Proteaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO5876 Dioclea grandiflora Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO4142 Ageratina glabrata Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13722 Rhizophora conjugata Species Rhizophoraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8967 Phellodendron sachalinense Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26627 Hypericum sarothra Species Hypericaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5876 Dioclea grandiflora Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8886 Protea mellifera Species Proteaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8054 Chara globularis Species Characeae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3558 Ophiura sarsi Species Ophiuridae 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
NPT108 Individual protein Estrogen receptor alpha Homo sapiens Activity = 20.0 % PMID[12350164]
NPT248 Individual protein Estrogen receptor beta Homo sapiens Activity = 20.0 % PMID[12350164]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT2 Others Unspecified n.a. IC50 = 3.2 ug.mL-1 PMID[12350164]
NPT2 Others Unspecified n.a. IC50 = 3.0 ug.mL-1 PMID[12350164]

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 NPC250214 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
0.7241 Intermediate Similarity NPC76372
0.7241 Intermediate Similarity NPC37496
0.6452 Remote Similarity NPC95936
0.6452 Remote Similarity NPC148757
0.619 Remote Similarity NPC265040
0.6094 Remote Similarity NPC480990
0.6032 Remote Similarity NPC107572
0.6032 Remote Similarity NPC32739
0.5909 Remote Similarity NPC291878
0.5909 Remote Similarity NPC608140
0.5846 Remote Similarity NPC66515
0.5846 Remote Similarity NPC310130
0.5846 Remote Similarity NPC610133
0.5821 Remote Similarity NPC161506
0.5806 Remote Similarity NPC259685
0.5781 Remote Similarity NPC1089
0.5781 Remote Similarity NPC306829
0.5735 Remote Similarity NPC473078
0.5692 Remote Similarity NPC149026
0.5692 Remote Similarity NPC187282
0.5692 Remote Similarity NPC69674
0.5667 Remote Similarity NPC255106
0.5667 Remote Similarity NPC235165
0.5606 Remote Similarity NPC220998
0.5588 Remote Similarity NPC36217
0.5522 Remote Similarity NPC76338
0.5522 Remote Similarity NPC250242
0.5455 Remote Similarity NPC75049
0.541 Remote Similarity NPC194432
0.541 Remote Similarity NPC215885
0.541 Remote Similarity NPC110038
0.5385 Remote Similarity NPC164980
0.5373 Remote Similarity NPC197252
0.5352 Remote Similarity NPC246948
0.5333 Remote Similarity NPC482487
0.5303 Remote Similarity NPC324436
0.5303 Remote Similarity NPC78
0.5303 Remote Similarity NPC150408
0.5294 Remote Similarity NPC285555
0.527 Remote Similarity NPC228779
0.527 Remote Similarity NPC483811
0.5238 Remote Similarity NPC2416
0.5224 Remote Similarity NPC175504
0.5217 Remote Similarity NPC485610
0.5217 Remote Similarity NPC182852
0.52 Remote Similarity NPC192686
0.52 Remote Similarity NPC284820
0.5167 Remote Similarity NPC213322
0.5161 Remote Similarity NPC110776
0.5139 Remote Similarity NPC166934
0.5132 Remote Similarity NPC119209
0.5082 Remote Similarity NPC248372
0.5082 Remote Similarity NPC482121
0.5082 Remote Similarity NPC270964
0.5075 Remote Similarity NPC236766

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC250214 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