Natural Product: NPC479876

Natural Product IDNPC479876
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 CWZLMWSCLBFCBY-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 188424
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0002585] O-methylated flavonoids
          • [CHEMONTID:0002590] 5-O-methylated flavonoids

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 CWZLMWSCLBFCBY-UHFFFAOYSA-N
Standard InCHI InChI=1S/C16H14O5/c1-20-14-6-11(18)7-15-16(14)12(19)8-13(21-15)9-2-4-10(17)5-3-9/h2-7,13,17-18H,8H2,1H3
SMILES COc1cc(cc2c1C(=O)CC(c1ccc(cc1)O)O2)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   286.08 Volume:   285.119
?
Van der Waals volume.
Dense:   1.003 LogP:   2.418
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.595
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.712
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   18.0
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:   0.887 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.798 Fsp3:   0.188
MCE-18:   54.579
?
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:   0 PAINS Alert:   0
Colloidal aggregators:   0.493 Fluc inhibitor:   0.48
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.278
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.337
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.37 Promiscuous compounds:   0.017

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.819 MDCK Permeability:   -4.768
Pgp-inhibitor:   0.701 Pgp-substrate:   0.032
PAMPA:   0.073
?
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):   0.0
20% Bioavailability (F20%):   0.005 30% Bioavailability (F30%):   0.379
50% Bioavailability (F50%):   0.985

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.81
Plasma Protein Binding (PPB):   93.859% Volume Distribution (VD):   0.019
Fu: 7.036%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.874
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   0.981
BSEP inhibitor:   0.992

ADMET: Metabolism

CYP1A2-inhibitor:   0.657 CYP1A2-substrate:   0.995
CYP2C19-inhibitor:   0.287 CYP2C19-substrate:   0.999
CYP2C9-inhibitor:   0.488 CYP2C9-substrate:   0.008
CYP2D6-inhibitor:   0.455 CYP2D6-substrate:   0.999
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.004
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.097
HLM stability:   0.821
?
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):  7.512 Half-life (T1/2):  1.23

ADMET: Toxicity

hERG Blockers:  0.247 hERG Blockers (10um):  0.619
Human Hepatotoxicity (H-HT):  0.712 Drug-induced Liver Injury (DILI):  0.376
AMES Toxicity:  0.656 Rat Oral Acute Toxicity:  0.518
Maximum Recommended Daily Dose:  0.689 Skin Sensitization:  0.572
Carcinogencity:  0.775 Eye Corrosion:  0.041
Eye Irritation:  0.987 Respiratory Toxicity:  0.522
Drug-induced Neurotoxicity:  0.586 Ototoxicity:  0.279
Hematotoxicity:  0.199 Drug-induced Nephrotoxicity:  0.313
Genotoxicity:  0.787 RPMI-8226 Immunitoxicity:  0.063
A549 Cytotoxicity:  0.218 Hek293 Cytotoxicity:  0.774
BCF:   1.164
?
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:   3.61
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.421
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.966
?
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
NPO6836 Alpinia blepharocalyx Species Zingiberaceae Eukaryota seeds Mengha, Yunnan Province, China 1991-Aug PMID[11277741]
NPO6836 Alpinia blepharocalyx Species Zingiberaceae Eukaryota seeds n.a. n.a. PMID[11325233]
NPO6836 Alpinia blepharocalyx Species Zingiberaceae Eukaryota Seeds n.a. n.a. PMID[11430002]
NPO6836 Alpinia blepharocalyx Species Zingiberaceae Eukaryota n.a. n.a. n.a. PMID[9461664]
NPO6836 Alpinia blepharocalyx Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO6836 Alpinia blepharocalyx Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO6836 Alpinia blepharocalyx Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO6836 Alpinia blepharocalyx Species Zingiberaceae 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
NPT21962 Single protein Methionyl-tRNA synthetase, putative Leishmania donovani (strain BPK282A1) Inhibition = 2.198 % DOI[10.6019/CHEMBL3988442]
NPT21963 Single protein Coenzyme A biosynthesis bifunctional protein CoaBC Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) IC50 > 30199.52 nM DOI[10.6019/CHEMBL3988442]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition = 57.7 % PMID[9461664]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition = 14.5 % PMID[9461664]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition = 26.2 % PMID[9461664]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition = 37.2 % PMID[9461664]
NPT2 Others Unspecified n.a. Inhibition = -13.99 % DOI[10.6019/CHEMBL3507680]

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 NPC479876 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 NPC225153
0.8372 Intermediate Similarity NPC265871
0.8372 Intermediate Similarity NPC205093
0.8182 Intermediate Similarity NPC188243
0.8182 Intermediate Similarity NPC110228
0.6957 Remote Similarity NPC329225
0.6957 Remote Similarity NPC147686
0.66 Remote Similarity NPC329203
0.66 Remote Similarity NPC222342
0.6531 Remote Similarity NPC32441
0.6531 Remote Similarity NPC79943
0.6471 Remote Similarity NPC606248
0.6327 Remote Similarity NPC476480
0.6327 Remote Similarity NPC84585
0.6154 Remote Similarity NPC210084
0.6154 Remote Similarity NPC475267
0.6078 Remote Similarity NPC177354
0.6034 Remote Similarity NPC76338
0.6034 Remote Similarity NPC250242
0.5968 Remote Similarity NPC169248
0.5968 Remote Similarity NPC72649
0.5962 Remote Similarity NPC300668
0.5962 Remote Similarity NPC324386
0.5862 Remote Similarity NPC470133
0.5849 Remote Similarity NPC485881
0.5769 Remote Similarity NPC1612
0.5769 Remote Similarity NPC183959
0.5745 Remote Similarity NPC228184
0.5741 Remote Similarity NPC599987
0.566 Remote Similarity NPC274784
0.566 Remote Similarity NPC20709
0.5614 Remote Similarity NPC169591
0.5614 Remote Similarity NPC298223
0.5614 Remote Similarity NPC604412
0.5593 Remote Similarity NPC470131
0.5593 Remote Similarity NPC470132
0.5577 Remote Similarity NPC243083
0.5577 Remote Similarity NPC264083
0.5577 Remote Similarity NPC13768
0.5577 Remote Similarity NPC287246
0.5577 Remote Similarity NPC603284
0.5556 Remote Similarity NPC469764
0.551 Remote Similarity NPC99854
0.5472 Remote Similarity NPC150648
0.5472 Remote Similarity NPC167624
0.5472 Remote Similarity NPC166482
0.5455 Remote Similarity NPC474208
0.5439 Remote Similarity NPC236637
0.5424 Remote Similarity NPC69674
0.5385 Remote Similarity NPC485619
0.537 Remote Similarity NPC99597
0.537 Remote Similarity NPC255106
0.537 Remote Similarity NPC235165
0.537 Remote Similarity NPC156057
0.5362 Remote Similarity NPC479540
0.5333 Remote Similarity NPC220998
0.5333 Remote Similarity NPC470135
0.5283 Remote Similarity NPC6407
0.5283 Remote Similarity NPC545184
0.5273 Remote Similarity NPC321011
0.5273 Remote Similarity NPC294852
0.5273 Remote Similarity NPC476153
0.5273 Remote Similarity NPC188679
0.5273 Remote Similarity NPC486095
0.5254 Remote Similarity NPC39329
0.5254 Remote Similarity NPC51032
0.5246 Remote Similarity NPC316816
0.5246 Remote Similarity NPC486094
0.5224 Remote Similarity NPC206378
0.52 Remote Similarity NPC93398
0.52 Remote Similarity NPC258979
0.52 Remote Similarity NPC8283
0.5185 Remote Similarity NPC37392
0.5098 Remote Similarity NPC192304
0.5091 Remote Similarity NPC194432
0.5091 Remote Similarity NPC338131
0.5088 Remote Similarity NPC302950
0.5082 Remote Similarity NPC68104

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC479876 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
0.6957 Remote Similarity NPD1549 Phase 2
0.6531 Remote Similarity NPD1552 Clinical (unspecified phase)
0.5577 Remote Similarity NPD1550 Phase 2
0.5088 Remote Similarity NPD1934 Phase 0

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