Natural Product: NPC204515

Natural Product IDNPC204515
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (2S)-Dihydrobaicalein
IUPAC Name (2S)-5,6,7-trihydroxy-2-phenyl-2,3-dihydrochromen-4-one
Synonyms (2S)-Dihydrobaicalein
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL402227
PubChem CID 14135323
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0000337] Flavans
          • [CHEMONTID:0001632] 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 GPDJGLOROGNHJD-NSHDSACASA-N
Standard InCHI InChI=1S/C15H12O5/c16-9-6-11(8-4-2-1-3-5-8)20-12-7-10(17)14(18)15(19)13(9)12/h1-5,7,11,17-19H,6H2/t11-/m0/s1
SMILES O=C1C[C@H](Oc2c1c(O)c(c(c2)O)O)c1ccccc1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   272.07 Volume:   267.823
?
Van der Waals volume.
Dense:   1.016 LogP:   2.447
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.602
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.698
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   18.0
TPSA:   86.99
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   3.0 Rings:   3.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.694 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.831 Fsp3:   0.133
MCE-18:   55.0
?
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:   1
Chelating Alert:   1 PAINS Alert:   1
Colloidal aggregators:   0.662 Fluc inhibitor:   0.641
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.186
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.205
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.551 Promiscuous compounds:   0.151

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.962 MDCK Permeability:   -4.759
Pgp-inhibitor:   0.939 Pgp-substrate:   0.003
PAMPA:   0.873
?
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%):   0.007 30% Bioavailability (F30%):   0.981
50% Bioavailability (F50%):   0.998

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.002 MRP1:   0.963
Plasma Protein Binding (PPB):   98.27% Volume Distribution (VD):   -0.191
Fu: 1.436%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.995
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.993
BSEP inhibitor:   0.849

ADMET: Metabolism

CYP1A2-inhibitor:   0.595 CYP1A2-substrate:   0.216
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.928
CYP2C9-inhibitor:   0.032 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.022 CYP2D6-substrate:   0.998
CYP3A4-inhibitor:   0.001 CYP3A4-substrate:   0.034
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.969
HLM stability:   0.998
?
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):  7.759 Half-life (T1/2):  1.449

ADMET: Toxicity

hERG Blockers:  0.104 hERG Blockers (10um):  0.692
Human Hepatotoxicity (H-HT):  0.716 Drug-induced Liver Injury (DILI):  0.446
AMES Toxicity:  0.751 Rat Oral Acute Toxicity:  0.461
Maximum Recommended Daily Dose:  0.566 Skin Sensitization:  0.992
Carcinogencity:  0.411 Eye Corrosion:  0.105
Eye Irritation:  0.996 Respiratory Toxicity:  0.084
Drug-induced Neurotoxicity:  0.434 Ototoxicity:  0.677
Hematotoxicity:  0.099 Drug-induced Nephrotoxicity:  0.326
Genotoxicity:  0.944 RPMI-8226 Immunitoxicity:  0.025
A549 Cytotoxicity:  0.757 Hek293 Cytotoxicity:  0.233
BCF:   1.201
?
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:   3.849
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.191
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.624
?
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
NPO33288 Brazilian Red Propolis Strain n.a. n.a. n.a. Brazilian n.a. PMID[17950610]
NPO33288 Brazilian Red Propolis Strain n.a. n.a. n.a. Brazilian n.a. PMID[18440233]
NPO33288 Brazilian Red Propolis Strain n.a. n.a. n.a. n.a. n.a. PMID[26938776]
NPO33288 Brazilian Red Propolis Strain n.a. n.a. n.a. n.a. n.a. PMID[32525315]
NPO8300 Apis mellifera ligustica Species Apidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO33288 Brazilian Red Propolis Strain n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO8300 Apis mellifera ligustica Species Apidae Eukaryota n.a. n.a. n.a. Database[TCMID]

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
NPT3414 Individual protein Serine/threonine-protein kinase PLK2 Homo sapiens IC50 = 242200.0 nM PMID[35878418]
NPT3358 Individual protein Serine/threonine-protein kinase PLK3 Homo sapiens IC50 = 1604000.0 nM PMID[35878418]
NPT831 Individual protein Serine/threonine-protein kinase PLK1 Homo sapiens IC50 = 6300.0 nM PMID[35878418]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT461 Cell line PANC-1 Homo sapiens CD100 > 100.0 uM PMID[17950610]
NPT81 Cell line A549 Homo sapiens IC50 > 100000.0 nM PMID[18440233]
NPT165 Cell line HeLa Homo sapiens IC50 > 100000.0 nM PMID[18440233]
NPT453 Cell line HT-1080 Homo sapiens IC50 > 100000.0 nM PMID[18440233]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 53400.0 nM PMID[18440233]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 > 100000.0 nM PMID[18440233]

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 NPC204515 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
0.6735 Remote Similarity NPC243083
0.6735 Remote Similarity NPC13768
0.6735 Remote Similarity NPC287246
0.66 Remote Similarity NPC312391
0.6471 Remote Similarity NPC255106
0.6471 Remote Similarity NPC482119
0.6471 Remote Similarity NPC235165
0.6471 Remote Similarity NPC482120
0.6275 Remote Similarity NPC150648
0.6 Remote Similarity NPC265871
0.6 Remote Similarity NPC205093
0.5965 Remote Similarity NPC39045
0.5962 Remote Similarity NPC37392
0.5882 Remote Similarity NPC476480
0.5882 Remote Similarity NPC84585
0.5849 Remote Similarity NPC194432
0.569 Remote Similarity NPC1089
0.5577 Remote Similarity NPC213322
0.5556 Remote Similarity NPC99597
0.5472 Remote Similarity NPC248372
0.5472 Remote Similarity NPC32441
0.5472 Remote Similarity NPC482121
0.5472 Remote Similarity NPC482487
0.5472 Remote Similarity NPC79943
0.5472 Remote Similarity NPC270964
0.5424 Remote Similarity NPC109183
0.5417 Remote Similarity NPC314329
0.5417 Remote Similarity NPC603208
0.537 Remote Similarity NPC177354
0.5333 Remote Similarity NPC175504
0.5306 Remote Similarity NPC228184
0.5273 Remote Similarity NPC274784
0.5273 Remote Similarity NPC300668
0.5273 Remote Similarity NPC20709
0.5273 Remote Similarity NPC215885
0.5273 Remote Similarity NPC110776
0.5273 Remote Similarity NPC324386
0.5273 Remote Similarity NPC110038
0.5246 Remote Similarity NPC470135
0.5185 Remote Similarity NPC6407
0.5185 Remote Similarity NPC545184
0.5179 Remote Similarity NPC321011
0.5179 Remote Similarity NPC294852
0.5179 Remote Similarity NPC188679
0.5179 Remote Similarity NPC606248
0.5172 Remote Similarity NPC35150
0.5172 Remote Similarity NPC106328
0.5088 Remote Similarity NPC2416
0.5088 Remote Similarity NPC271590

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC204515 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
0.6735 Remote Similarity NPD1550 Phase 2
0.5472 Remote Similarity NPD1552 Clinical (unspecified phase)
0.5417 Remote Similarity NPD1547 Clinical (unspecified phase)

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