Natural Product: NPC27124

Natural Product IDNPC27124
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 UVDNRKMZMPBBTJ-ZFWWWQNUSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0000337] Flavans
          • [CHEMONTID:0003012] Flavan-3-ols
            • [CHEMONTID:0001584] Catechins

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 UVDNRKMZMPBBTJ-ZFWWWQNUSA-N
Standard InCHI InChI=1S/C15H14O7/c16-6-1-9(17)7-3-13(21)15(22-14(7)2-6)8-4-11(19)12(20)5-10(8)18/h1-2,4-5,13,15-21H,3H2/t13-,15-/m0/s1
SMILES c1c(cc2c(C[C@@H]([C@H](c3cc(c(cc3O)O)O)O2)O)c1O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   306.07 Volume:   288.04
?
Van der Waals volume.
Dense:   1.063 LogP:   0.323
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   0.804
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.229
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   17.0
TPSA:   130.61
?
Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   6.0 Rings:   3.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.345 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.546 Fsp3:   0.2
MCE-18:   63.333
?
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:   0.74 Fluc inhibitor:   0.545
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.593
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.023
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.525 Promiscuous compounds:   0.455

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.328 MDCK Permeability:   -4.945
Pgp-inhibitor:   0.0 Pgp-substrate:   0.21
PAMPA:   0.863
?
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):   0.002
20% Bioavailability (F20%):   0.725 30% Bioavailability (F30%):   0.973
50% Bioavailability (F50%):   0.998

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.911
Plasma Protein Binding (PPB):   93.431% Volume Distribution (VD):   -0.016
Fu: 12.394%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.738
OATP1B3 inhibitor:   0.764 BCRP inhibitor:   0.046
BSEP inhibitor:   0.078

ADMET: Metabolism

CYP1A2-inhibitor:   0.961 CYP1A2-substrate:   0.008
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.013
CYP2C9-inhibitor:   0.718 CYP2C9-substrate:   0.001
CYP2D6-inhibitor:   0.947 CYP2D6-substrate:   0.333
CYP3A4-inhibitor:   0.006 CYP3A4-substrate:   0.069
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.963
HLM stability:   0.162
?
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):  8.223 Half-life (T1/2):  2.853

ADMET: Toxicity

hERG Blockers:  0.054 hERG Blockers (10um):  0.673
Human Hepatotoxicity (H-HT):  0.722 Drug-induced Liver Injury (DILI):  0.079
AMES Toxicity:  0.636 Rat Oral Acute Toxicity:  0.477
Maximum Recommended Daily Dose:  0.872 Skin Sensitization:  0.925
Carcinogencity:  0.175 Eye Corrosion:  0.009
Eye Irritation:  0.995 Respiratory Toxicity:  0.689
Drug-induced Neurotoxicity:  0.023 Ototoxicity:  0.748
Hematotoxicity:  0.024 Drug-induced Nephrotoxicity:  0.1
Genotoxicity:  0.948 RPMI-8226 Immunitoxicity:  0.039
A549 Cytotoxicity:  0.76 Hek293 Cytotoxicity:  0.711
BCF:   0.921
?
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:   3.2
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.4
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.779
?
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
NPO19472 Thymus vulgaris Species Lamiaceae Eukaryota Leaves n.a. n.a. PMID[12088434]
NPO22423 Microtropis fokienensis Species Celastraceae Eukaryota stem n.a. n.a. PMID[16643054]
NPO22423 Microtropis fokienensis Species Celastraceae Eukaryota leaves n.a. n.a. PMID[17125218]
NPO22423 Microtropis fokienensis Species Celastraceae Eukaryota roots n.a. n.a. PMID[17315960]
NPO22423 Microtropis fokienensis Species Celastraceae Eukaryota n.a. root n.a. PMID[17315960]
NPO22423 Microtropis fokienensis Species Celastraceae Eukaryota n.a. n.a. n.a. PMID[18590313]
NPO22791 Astraeus pteridis Species Astraeaceae Eukaryota n.a. n.a. n.a. PMID[19067555]
NPO19472 Thymus vulgaris Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[21707257]
NPO19472 Thymus vulgaris Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[29726697]
NPO19472 Thymus vulgaris Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[34443694]
NPO19472 Thymus vulgaris Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[34770961]
NPO19472 Thymus vulgaris Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[35631245]
NPO19472 Thymus vulgaris Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[36840093]
NPO19472 Thymus vulgaris Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[37020229]
NPO19472 Thymus vulgaris Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[37226152]
NPO19472 Thymus vulgaris Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[38257205]
NPO19472 Thymus vulgaris Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[38370080]
NPO19472 Thymus vulgaris Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[38381096]
NPO19472 Thymus vulgaris Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[38695450]
NPO19472 Thymus vulgaris Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[39407547]
NPO23494 Centaurea linifolia Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5054 Limonium gmelinii Species Plumbaginaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO22423 Microtropis fokienensis Species Celastraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19472 Thymus vulgaris Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19472 Thymus vulgaris Species Lamiaceae Eukaryota Essential Oil n.a. n.a. Database[FooDB]
NPO19472 Thymus vulgaris Species Lamiaceae Eukaryota Leaf n.a. n.a. Database[FooDB]
NPO19472 Thymus vulgaris Species Lamiaceae Eukaryota Plant n.a. n.a. Database[FooDB]
NPO19472 Thymus vulgaris Species Lamiaceae Eukaryota Shoot n.a. n.a. Database[FooDB]
NPO19472 Thymus vulgaris Species Lamiaceae Eukaryota n.a. n.a. Database[FooDB]
NPO4594 Vitellaria paradoxa Species Sapotaceae Eukaryota n.a. n.a. Database[FooDB]
NPO19472 Thymus vulgaris Species Lamiaceae Eukaryota n.a. n.a. Database[FooDB]
NPO4594 Vitellaria paradoxa Species Sapotaceae Eukaryota n.a. n.a. Database[FooDB]
NPO5054 Limonium gmelinii Species Plumbaginaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO19472 Thymus vulgaris Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO19472 Thymus vulgaris Species Lamiaceae Eukaryota n.a. n.a. Database[Phenol-Explorer]
NPO19472 Thymus vulgaris Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO5054 Limonium gmelinii Species Plumbaginaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO5054 Limonium gmelinii Species Plumbaginaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO19472 Thymus vulgaris Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO19472 Thymus vulgaris Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO23494 Centaurea linifolia Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21956 Alyxia reinwardtii Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23879 Serratula inermis Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4594 Vitellaria paradoxa Species Sapotaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19472 Thymus vulgaris Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20604 Cneoridium dumosum Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22423 Microtropis fokienensis Species Celastraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25848 Oscillochloris trichoides Species Oscillochloridaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO5054 Limonium gmelinii Species Plumbaginaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22791 Astraeus pteridis Species Astraeaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24327 Machilus macrantha Species Lauraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23954 Tridachia crispata n.a. n.a. n.a. 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

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 NPC27124 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
0.7143 Intermediate Similarity NPC261619
0.7143 Intermediate Similarity NPC61477
0.7143 Intermediate Similarity NPC78770
0.7143 Intermediate Similarity NPC219876
0.7143 Intermediate Similarity NPC126029
0.7143 Intermediate Similarity NPC15658
0.7083 Intermediate Similarity NPC268266
0.7083 Intermediate Similarity NPC42760
0.7083 Intermediate Similarity NPC220825
0.7083 Intermediate Similarity NPC268342
0.6735 Remote Similarity NPC207179
0.6735 Remote Similarity NPC167571
0.6735 Remote Similarity NPC278552
0.6471 Remote Similarity NPC47398
0.6471 Remote Similarity NPC234333
0.6471 Remote Similarity NPC260898
0.6111 Remote Similarity NPC61946
0.5893 Remote Similarity NPC16435
0.5893 Remote Similarity NPC171932
0.5397 Remote Similarity NPC9636
0.5397 Remote Similarity NPC607430
0.5385 Remote Similarity NPC28440
0.5156 Remote Similarity NPC58190
0.5156 Remote Similarity NPC108811
0.5156 Remote Similarity NPC170103
0.5156 Remote Similarity NPC236202
0.5156 Remote Similarity NPC262911
0.5156 Remote Similarity NPC202742
0.5152 Remote Similarity NPC308402
0.5079 Remote Similarity NPC96576
0.5077 Remote Similarity NPC246202
0.5077 Remote Similarity NPC224161
0.5077 Remote Similarity NPC46335
0.5077 Remote Similarity NPC294558
0.5077 Remote Similarity NPC18185
0.5077 Remote Similarity NPC263940
0.5077 Remote Similarity NPC279406
0.5077 Remote Similarity NPC486519

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC27124 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
0.7143 Intermediate Similarity NPD1612 Clinical (unspecified phase)
0.7143 Intermediate Similarity NPD1613 Phase 4

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