Natural Product: NPC606248

Natural Product IDNPC606248
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 FCXRFTLSXMRXTM-LBPRGKRZSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL4866784
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]

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 FCXRFTLSXMRXTM-LBPRGKRZSA-N
Standard InCHI InChI=1S/C16H14O6/c1-21-16-11(19)7-13-14(15(16)20)10(18)6-12(22-13)8-2-4-9(17)5-3-8/h2-5,7,12,17,19-20H,6H2,1H3/t12-/m0/s1
SMILES COc1c(O)cc2c(c1O)C(=O)C[C@@H](c1ccc(O)cc1)O2

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   302.08 Volume:   293.909
?
Van der Waals volume.
Dense:   1.028 LogP:   2.463
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.56
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.251
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   18.0
TPSA:   96.22
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   3.0 Rings:   3.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.789 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.969 Fsp3:   0.188
MCE-18:   57.789
?
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:   0
Colloidal aggregators:   0.614 Fluc inhibitor:   0.788
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.235
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.257
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.36 Promiscuous compounds:   0.105

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.067 MDCK Permeability:   -4.802
Pgp-inhibitor:   0.972 Pgp-substrate:   0.151
PAMPA:   0.352
?
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):   0.001
20% Bioavailability (F20%):   0.001 30% Bioavailability (F30%):   0.74
50% Bioavailability (F50%):   0.997

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.879
Plasma Protein Binding (PPB):   95.959% Volume Distribution (VD):   -0.401
Fu: 4.256%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.995
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.997
BSEP inhibitor:   0.911

ADMET: Metabolism

CYP1A2-inhibitor:   0.962 CYP1A2-substrate:   0.112
CYP2C19-inhibitor:   0.084 CYP2C19-substrate:   0.856
CYP2C9-inhibitor:   0.402 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.535 CYP2D6-substrate:   0.999
CYP3A4-inhibitor:   0.001 CYP3A4-substrate:   0.169
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.933
HLM stability:   0.979
?
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):  4.71 Half-life (T1/2):  1.373

ADMET: Toxicity

hERG Blockers:  0.091 hERG Blockers (10um):  0.487
Human Hepatotoxicity (H-HT):  0.681 Drug-induced Liver Injury (DILI):  0.235
AMES Toxicity:  0.622 Rat Oral Acute Toxicity:  0.447
Maximum Recommended Daily Dose:  0.527 Skin Sensitization:  0.834
Carcinogencity:  0.57 Eye Corrosion:  0.039
Eye Irritation:  0.994 Respiratory Toxicity:  0.188
Drug-induced Neurotoxicity:  0.735 Ototoxicity:  0.334
Hematotoxicity:  0.15 Drug-induced Nephrotoxicity:  0.506
Genotoxicity:  0.877 RPMI-8226 Immunitoxicity:  0.12
A549 Cytotoxicity:  0.384 Hek293 Cytotoxicity:  0.601
BCF:   0.933
?
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:   3.517
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.636
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.015
?
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
NPO28877 Scutellaria baicalensis Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[19829679]
NPO28877 Scutellaria baicalensis Species Lamiaceae Eukaryota n.a. root n.a. PMID[21087019]
NPO28877 Scutellaria baicalensis Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[22314230]
NPO28877 Scutellaria baicalensis Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[23521110]
NPO28877 Scutellaria baicalensis Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[37569279]
NPO28877 Scutellaria baicalensis Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[9834167]
NPO28877 Scutellaria baicalensis Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28877 Scutellaria baicalensis Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO28877 Scutellaria baicalensis Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO28877 Scutellaria baicalensis Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO28877 Scutellaria baicalensis Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO28877 Scutellaria baicalensis Species Lamiaceae 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
NPT30060 Protein-protein interaction PCSK9/LDLR Homo sapiens Inhibition n.a. n.a. % PMID[33567826]

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 NPC606248 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
0.8125 Intermediate Similarity NPC255106
0.8125 Intermediate Similarity NPC235165
0.7843 Intermediate Similarity NPC474836
0.6923 Remote Similarity NPC475267
0.6731 Remote Similarity NPC329203
0.6731 Remote Similarity NPC324386
0.6731 Remote Similarity NPC222342
0.6667 Remote Similarity NPC32441
0.6667 Remote Similarity NPC79943
0.6471 Remote Similarity NPC225153
0.6471 Remote Similarity NPC479876
0.6415 Remote Similarity NPC300668
0.6078 Remote Similarity NPC329225
0.6078 Remote Similarity NPC147686
0.6 Remote Similarity NPC210084
0.5862 Remote Similarity NPC236637
0.5818 Remote Similarity NPC274784
0.5818 Remote Similarity NPC20709
0.5714 Remote Similarity NPC485881
0.5714 Remote Similarity NPC469764
0.5574 Remote Similarity NPC69674
0.5517 Remote Similarity NPC302950
0.5484 Remote Similarity NPC470131
0.5484 Remote Similarity NPC470133
0.5484 Remote Similarity NPC220998
0.5484 Remote Similarity NPC470135
0.5484 Remote Similarity NPC470132
0.5455 Remote Similarity NPC243083
0.5455 Remote Similarity NPC13768
0.5455 Remote Similarity NPC6407
0.5455 Remote Similarity NPC287246
0.5455 Remote Similarity NPC545184
0.5455 Remote Similarity NPC603284
0.5439 Remote Similarity NPC321011
0.5439 Remote Similarity NPC294852
0.5439 Remote Similarity NPC188679
0.5439 Remote Similarity NPC486095
0.5397 Remote Similarity NPC134171
0.5397 Remote Similarity NPC486094
0.537 Remote Similarity NPC265871
0.537 Remote Similarity NPC205093
0.5357 Remote Similarity NPC150648
0.5357 Remote Similarity NPC312391
0.5357 Remote Similarity NPC167624
0.5357 Remote Similarity NPC166482
0.5345 Remote Similarity NPC48208
0.5323 Remote Similarity NPC477841
0.5273 Remote Similarity NPC476480
0.5273 Remote Similarity NPC188243
0.5273 Remote Similarity NPC110228
0.5273 Remote Similarity NPC84585
0.5263 Remote Similarity NPC99597
0.5263 Remote Similarity NPC480993
0.5263 Remote Similarity NPC338131
0.5246 Remote Similarity NPC169591
0.5246 Remote Similarity NPC298223
0.5246 Remote Similarity NPC604412
0.5238 Remote Similarity NPC477840
0.5179 Remote Similarity NPC295261
0.5179 Remote Similarity NPC296490
0.5179 Remote Similarity NPC204515
0.5088 Remote Similarity NPC1612
0.5088 Remote Similarity NPC183959
0.5088 Remote Similarity NPC37392
0.5088 Remote Similarity NPC162869
0.5085 Remote Similarity NPC18727
0.5085 Remote Similarity NPC310135
0.5085 Remote Similarity NPC601395
0.5075 Remote Similarity NPC611447
0.507 Remote Similarity NPC601453
0.507 Remote Similarity NPC605491

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC606248 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
0.6667 Remote Similarity NPD1552 Clinical (unspecified phase)
0.6078 Remote Similarity NPD1549 Phase 2
0.5517 Remote Similarity NPD1934 Phase 0
0.5455 Remote Similarity NPD1550 Phase 2

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