Natural Product: NPC67805

Natural Product IDNPC67805
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Minimiflorin
IUPAC Name (8S)-5-hydroxy-8-(2-hydroxyphenyl)-2,2-dimethyl-10-(3-methylbut-2-enyl)-7,8-dihydropyrano[3,2-g]chromen-6-one
Synonyms Minimiflorin
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL464778
PubChem CID 180733
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 IAKVRAMIQPWTDR-FQEVSTJZSA-N
Standard InCHI InChI=1S/C25H26O5/c1-14(2)9-10-17-23-16(11-12-25(3,4)30-23)22(28)21-19(27)13-20(29-24(17)21)15-7-5-6-8-18(15)26/h5-9,11-12,20,26,28H,10,13H2,1-4H3/t20-/m0/s1
SMILES CC(=CCc1c2c(C=CC(C)(C)O2)c(c2C(=O)C[C@@H](c3ccccc3O)Oc12)O)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   406.18 Volume:   426.953
?
Van der Waals volume.
Dense:   0.951 LogP:   5.134
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.967
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.324
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   24.0
TPSA:   75.99
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   2.0 Rings:   4.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.659 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.617 Fsp3:   0.32
MCE-18:   82.727
?
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:   0 PAINS Alert:   0
Colloidal aggregators:   0.979 Fluc inhibitor:   0.469
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.784
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.809
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.24 Promiscuous compounds:   0.102

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.947 MDCK Permeability:   -4.711
Pgp-inhibitor:   0.995 Pgp-substrate:   0.004
PAMPA:   0.479
?
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):   0.017
20% Bioavailability (F20%):   0.81 30% Bioavailability (F30%):   0.981
50% Bioavailability (F50%):   0.998

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.071 MRP1:   0.966
Plasma Protein Binding (PPB):   96.587% Volume Distribution (VD):   0.179
Fu: 3.003%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   0.768 BCRP inhibitor:   0.848
BSEP inhibitor:   0.997

ADMET: Metabolism

CYP1A2-inhibitor:   0.004 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.579 CYP2C19-substrate:   1.0
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.165
CYP3A4-inhibitor:   0.936 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):  4.57 Half-life (T1/2):  1.214

ADMET: Toxicity

hERG Blockers:  0.072 hERG Blockers (10um):  0.493
Human Hepatotoxicity (H-HT):  0.836 Drug-induced Liver Injury (DILI):  0.447
AMES Toxicity:  0.742 Rat Oral Acute Toxicity:  0.911
Maximum Recommended Daily Dose:  0.806 Skin Sensitization:  0.973
Carcinogencity:  0.314 Eye Corrosion:  0.0
Eye Irritation:  0.713 Respiratory Toxicity:  0.972
Drug-induced Neurotoxicity:  0.771 Ototoxicity:  0.648
Hematotoxicity:  0.174 Drug-induced Nephrotoxicity:  0.895
Genotoxicity:  0.951 RPMI-8226 Immunitoxicity:  0.175
A549 Cytotoxicity:  0.805 Hek293 Cytotoxicity:  0.547
BCF:   2.035
?
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:   5.054
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   7.164
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   6.543
?
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
NPO24957 Bucida buceras Species Combretaceae Eukaryota n.a. n.a. n.a. PMID[12542360]
NPO28183 Cymbopogon flexuosus Species Poaceae Eukaryota n.a. n.a. n.a. PMID[34946632]
NPO28183 Cymbopogon flexuosus Species Poaceae Eukaryota n.a. n.a. n.a. PMID[38370218]
NPO24957 Bucida buceras Species Combretaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28183 Cymbopogon flexuosus Species Poaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14464 Oxalis triangularis Species Oxalidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28353 Schizanthus pinnatus Species Solanaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28183 Cymbopogon flexuosus Species Poaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO28183 Cymbopogon flexuosus Species Poaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO28564 Pterorhachis zenkeri Species Meliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28411 Hedysarum setigerum Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24957 Bucida buceras Species Combretaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11029 Bessera tenuiflora Species Asparagaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28235 Heimia montana Species Lythraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28353 Schizanthus pinnatus Species Solanaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14464 Oxalis triangularis Species Oxalidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28113 Oria flava n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO28736 Wedelia paludosa Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28183 Cymbopogon flexuosus Species Poaceae 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 IC50 = 7.3 ug.mL-1 PMID[12542360]
NPT81 Cell line A549 Homo sapiens IC50 = 8.0 ug.mL-1 PMID[12542360]
NPT309 Cell line 1A9 Homo sapiens IC50 = 7.6 ug.mL-1 PMID[12542360]
NPT180 Cell line HCT-8 Homo sapiens IC50 = 7.2 ug.mL-1 PMID[12542360]
NPT83 Cell line MCF7 Homo sapiens IC50 = 7.5 ug.mL-1 PMID[12542360]
NPT306 Cell line PC-3 Homo sapiens IC50 = 9.8 ug.mL-1 PMID[12542360]
NPT147 Cell line SK-MEL-2 Homo sapiens IC50 = 9.0 ug.mL-1 PMID[12542360]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 7.7 ug.mL-1 PMID[12542360]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 11.0 ug.mL-1 PMID[12542360]

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 NPC67805 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
0.8358 Intermediate Similarity NPC195621
0.7971 Intermediate Similarity NPC83357
0.7761 Intermediate Similarity NPC142405
0.7083 Intermediate Similarity NPC304207
0.6892 Remote Similarity NPC236756
0.6667 Remote Similarity NPC20488
0.6486 Remote Similarity NPC214774
0.6104 Remote Similarity NPC609256
0.6087 Remote Similarity NPC306829
0.6081 Remote Similarity NPC246948
0.6 Remote Similarity NPC248793
0.5897 Remote Similarity NPC54577
0.5846 Remote Similarity NPC101752
0.5833 Remote Similarity NPC234629
0.5789 Remote Similarity NPC48579
0.5658 Remote Similarity NPC483807
0.5625 Remote Similarity NPC119209
0.5556 Remote Similarity NPC283234
0.55 Remote Similarity NPC192686
0.55 Remote Similarity NPC284820
0.5467 Remote Similarity NPC470647
0.5443 Remote Similarity NPC207809
0.5443 Remote Similarity NPC483808
0.5443 Remote Similarity NPC259710
0.5244 Remote Similarity NPC483809
0.5217 Remote Similarity NPC324134
0.5217 Remote Similarity NPC40833
0.52 Remote Similarity NPC285555
0.5181 Remote Similarity NPC483810
0.5132 Remote Similarity NPC182852
0.5128 Remote Similarity NPC81697
0.5128 Remote Similarity NPC485615
0.5116 Remote Similarity NPC301256
0.5067 Remote Similarity NPC220998
0.5063 Remote Similarity NPC39752
0.5062 Remote Similarity NPC267375
0.506 Remote Similarity NPC132592

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC67805 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