Natural Product: NPC325028

Natural Product IDNPC325028
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Dihydrobinetin
IUPAC Name 3,7-dihydroxy-2-(3,4,5-trihydroxyphenyl)-2,3-dihydrochromen-4-one
Synonyms NSC-59266
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL444171
PubChem CID 20399
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0000337] Flavans
          • [CHEMONTID:0001632] Flavanones
            • [CHEMONTID:0001362] Flavanonols

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 VSJCDPYIMBSOKN-UHFFFAOYSA-N
Standard InCHI InChI=1S/C15H12O7/c16-7-1-2-8-11(5-7)22-15(14(21)12(8)19)6-3-9(17)13(20)10(18)4-6/h1-5,14-18,20-21H
SMILES C1=CC2=C(C=C1O)OC(C(C2=O)O)C3=CC(=C(C(=C3)O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   304.06 Volume:   285.403
?
Van der Waals volume.
Dense:   1.065 LogP:   0.578
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   0.888
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.738
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   18.0
TPSA:   127.45
?
Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   5.0 Rings:   3.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.501 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.401 Fsp3:   0.133
MCE-18:   61.471
?
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:   0.613 Fluc inhibitor:   0.75
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.347
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.263
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.647 Promiscuous compounds:   0.63

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.943 MDCK Permeability:   -4.902
Pgp-inhibitor:   0.0 Pgp-substrate:   0.05
PAMPA:   0.963
?
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):   0.476
20% Bioavailability (F20%):   0.923 30% Bioavailability (F30%):   0.994
50% Bioavailability (F50%):   0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.001 MRP1:   0.74
Plasma Protein Binding (PPB):   90.761% Volume Distribution (VD):   -0.223
Fu: 11.594%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.862
OATP1B3 inhibitor:   0.994 BCRP inhibitor:   0.636
BSEP inhibitor:   0.009

ADMET: Metabolism

CYP1A2-inhibitor:   0.033 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.329
CYP2C9-inhibitor:   0.001 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   1.0
CYP3A4-inhibitor:   0.001 CYP3A4-substrate:   0.037
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.893
HLM stability:   0.465
?
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):  7.001 Half-life (T1/2):  2.282

ADMET: Toxicity

hERG Blockers:  0.087 hERG Blockers (10um):  0.83
Human Hepatotoxicity (H-HT):  0.434 Drug-induced Liver Injury (DILI):  0.475
AMES Toxicity:  0.62 Rat Oral Acute Toxicity:  0.448
Maximum Recommended Daily Dose:  0.677 Skin Sensitization:  0.984
Carcinogencity:  0.46 Eye Corrosion:  0.011
Eye Irritation:  0.972 Respiratory Toxicity:  0.396
Drug-induced Neurotoxicity:  0.018 Ototoxicity:  0.892
Hematotoxicity:  0.026 Drug-induced Nephrotoxicity:  0.025
Genotoxicity:  0.975 RPMI-8226 Immunitoxicity:  0.008
A549 Cytotoxicity:  0.851 Hek293 Cytotoxicity:  0.524
BCF:   0.797
?
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:   3.35
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.459
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.878
?
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
NPO3634 Robinia pseudoacacia Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[11551759]
NPO3634 Robinia pseudoacacia Species Fabaceae Eukaryota n.a. whole plant n.a. PMID[21214467]
NPO3634 Robinia pseudoacacia Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3634 Robinia pseudoacacia Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO3634 Robinia pseudoacacia Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO3634 Robinia pseudoacacia Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO3634 Robinia pseudoacacia 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

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT91 Cell line KB Homo sapiens ED50 = 23.0 ug ml-1 PMID[469554]
NPT367 Cell line MDA-N Homo sapiens GI50 n.a. 18365.38 nM PubChem BioAssay data set
NPT368 Cell line SN12C Homo sapiens GI50 n.a. 20417.38 nM PubChem BioAssay data set
NPT370 Cell line NCI-H23 Homo sapiens GI50 n.a. 34514.37 nM PubChem BioAssay data set
NPT369 Cell line ACHN Homo sapiens GI50 n.a. 25822.6 nM PubChem BioAssay data set
NPT371 Cell line UO-31 Homo sapiens GI50 n.a. 67764.15 nM PubChem BioAssay data set
NPT372 Cell line HOP-92 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT90 Cell line DU-145 Homo sapiens GI50 n.a. 47315.13 nM PubChem BioAssay data set
NPT116 Cell line HL-60 Homo sapiens GI50 n.a. 19860.95 nM PubChem BioAssay data set
NPT374 Cell line SF-539 Homo sapiens GI50 n.a. 21527.82 nM PubChem BioAssay data set
NPT373 Cell line SK-MEL-5 Homo sapiens GI50 n.a. 33036.95 nM PubChem BioAssay data set
NPT375 Cell line Malme-3M Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT376 Cell line A498 Homo sapiens GI50 n.a. 28119.01 nM PubChem BioAssay data set
NPT377 Cell line OVCAR-3 Homo sapiens GI50 n.a. 47863.01 nM PubChem BioAssay data set
NPT112 Cell line MOLT-4 Homo sapiens GI50 n.a. 19054.61 nM PubChem BioAssay data set
NPT379 Cell line HOP-62 Homo sapiens GI50 n.a. 35481.34 nM PubChem BioAssay data set
NPT378 Cell line NCI/ADR-RES Homo sapiens GI50 n.a. 25061.09 nM PubChem BioAssay data set
NPT380 Cell line U-251 Homo sapiens GI50 n.a. 22490.55 nM PubChem BioAssay data set
NPT381 Cell line OVCAR-8 Homo sapiens GI50 n.a. 21978.6 nM PubChem BioAssay data set
NPT382 Cell line OVCAR-5 Homo sapiens GI50 n.a. 58210.32 nM PubChem BioAssay data set
NPT82 Cell line MDA-MB-231 Homo sapiens GI50 n.a. 21134.89 nM PubChem BioAssay data set
NPT383 Cell line SNB-19 Homo sapiens GI50 n.a. 41399.97 nM PubChem BioAssay data set
NPT385 Cell line SR Homo sapiens GI50 n.a. 20464.45 nM PubChem BioAssay data set
NPT384 Cell line TK-10 Homo sapiens GI50 n.a. 23550.49 nM PubChem BioAssay data set
NPT323 Cell line SW-620 Homo sapiens GI50 n.a. 25003.45 nM PubChem BioAssay data set
NPT455 Cell line NCI-H522 Homo sapiens GI50 n.a. 24831.33 nM PubChem BioAssay data set
NPT386 Cell line KM12 Homo sapiens GI50 n.a. 26668.59 nM PubChem BioAssay data set
NPT387 Cell line M14 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT388 Cell line NCI-H322M Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT389 Cell line RPMI-8226 Homo sapiens GI50 n.a. 17782.79 nM PubChem BioAssay data set
NPT456 Cell line OVCAR-4 Homo sapiens GI50 n.a. 37931.5 nM PubChem BioAssay data set
NPT390 Cell line LOX IMVI Homo sapiens GI50 n.a. 19142.56 nM PubChem BioAssay data set
NPT457 Cell line BT-549 Homo sapiens GI50 n.a. 20511.62 nM PubChem BioAssay data set
NPT147 Cell line SK-MEL-2 Homo sapiens GI50 n.a. 33113.11 nM PubChem BioAssay data set
NPT391 Cell line HCC 2998 Homo sapiens GI50 n.a. 31550.05 nM PubChem BioAssay data set
NPT81 Cell line A549 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT148 Cell line HCT-15 Homo sapiens GI50 n.a. 33728.73 nM PubChem BioAssay data set
NPT393 Cell line HCT-116 Homo sapiens GI50 n.a. 21978.6 nM PubChem BioAssay data set
NPT395 Cell line SF-268 Homo sapiens GI50 n.a. 34119.29 nM PubChem BioAssay data set
NPT394 Cell line EKVX Homo sapiens GI50 n.a. 19010.78 nM PubChem BioAssay data set
NPT306 Cell line PC-3 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT83 Cell line MCF7 Homo sapiens GI50 n.a. 25703.96 nM PubChem BioAssay data set
NPT146 Cell line SK-OV-3 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT396 Cell line T47D Homo sapiens GI50 n.a. 37844.26 nM PubChem BioAssay data set
NPT397 Cell line NCI-H460 Homo sapiens GI50 n.a. 19815.27 nM PubChem BioAssay data set
NPT308 Cell line CAKI-1 Homo sapiens GI50 n.a. 53826.98 nM PubChem BioAssay data set
NPT398 Cell line UACC-62 Homo sapiens GI50 n.a. 30130.06 nM PubChem BioAssay data set
NPT400 Cell line MDA-MB-435 Homo sapiens GI50 n.a. 19769.7 nM PubChem BioAssay data set
NPT399 Cell line SF-295 Homo sapiens GI50 n.a. 21827.3 nM PubChem BioAssay data set
NPT458 Cell line IGROV-1 Homo sapiens GI50 n.a. 18030.18 nM PubChem BioAssay data set
NPT402 Cell line Hs-578T Homo sapiens GI50 n.a. 70145.53 nM PubChem BioAssay data set
NPT401 Cell line 786-0 Homo sapiens GI50 n.a. 23823.19 nM PubChem BioAssay data set
NPT403 Cell line UACC-257 Homo sapiens GI50 n.a. 34753.62 nM PubChem BioAssay data set
NPT404 Cell line CCRF-CEM Homo sapiens GI50 n.a. 24099.05 nM PubChem BioAssay data set
NPT405 Cell line NCI-H226 Homo sapiens GI50 n.a. 39084.09 nM PubChem BioAssay data set
NPT139 Cell line HT-29 Homo sapiens GI50 n.a. 23442.29 nM PubChem BioAssay data set
NPT170 Cell line SK-MEL-28 Homo sapiens GI50 n.a. 46773.51 nM PubChem BioAssay data set
NPT406 Cell line RXF 393 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT407 Cell line COLO 205 Homo sapiens GI50 n.a. 32359.37 nM PubChem BioAssay data set
NPT175 Organism Enterococcus faecalis Enterococcus faecalis MIC = 256.0 ug.mL-1 PMID[19236029]
NPT175 Organism Enterococcus faecalis Enterococcus faecalis MIC > 512.0 ug.mL-1 PMID[19236029]
NPT2 Others Unspecified n.a. Activity = 7.94 10'6/M PMID[19236029]

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 NPC325028 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 NPC256346
1.0 High Similarity NPC606550
0.8298 Intermediate Similarity NPC246328
0.8298 Intermediate Similarity NPC27532
0.7826 Intermediate Similarity NPC1940
0.76 Intermediate Similarity NPC609065
0.75 Intermediate Similarity NPC148011
0.6863 Remote Similarity NPC19721
0.6667 Remote Similarity NPC52530
0.6 Remote Similarity NPC36835
0.6 Remote Similarity NPC246162
0.6 Remote Similarity NPC9743
0.6 Remote Similarity NPC260491
0.6 Remote Similarity NPC61506
0.6 Remote Similarity NPC240476
0.5926 Remote Similarity NPC201837
0.5741 Remote Similarity NPC62290
0.5741 Remote Similarity NPC142731
0.5741 Remote Similarity NPC326506
0.5614 Remote Similarity NPC611035
0.5556 Remote Similarity NPC21835
0.5455 Remote Similarity NPC1612
0.5455 Remote Similarity NPC183959
0.5455 Remote Similarity NPC600246
0.5263 Remote Similarity NPC176869
0.5263 Remote Similarity NPC3779
0.5185 Remote Similarity NPC601844
0.5179 Remote Similarity NPC279417
0.5179 Remote Similarity NPC4152
0.5179 Remote Similarity NPC49130
0.5172 Remote Similarity NPC250922
0.5091 Remote Similarity NPC268266
0.5091 Remote Similarity NPC42760
0.5091 Remote Similarity NPC220825
0.5091 Remote Similarity NPC268342

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC325028 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