Natural Product: NPC23467

Natural Product IDNPC23467
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 AOJJSUZBOXZQNB-XITUYBAUSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 92249481
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0002106] Anthracyclines

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 AOJJSUZBOXZQNB-XITUYBAUSA-N
Standard InCHI InChI=1S/C27H29NO11/c1-10-22(31)13(28)6-17(38-10)39-15-8-27(36,16(30)9-29)7-12-19(15)26(35)21-20(24(12)33)23(32)11-4-3-5-14(37-2)18(11)25(21)34/h3-5,10,13,15,17,22,29,31,33,35-36H,6-9,28H2,1-2H3/t10-,13-,15+,17+,22-,27+/m1/s1
SMILES C[C@@H]1[C@H]([C@@H](C[C@@H](O1)O[C@H]1C[C@@](Cc2c1c(c1c(C(=O)c3cccc(c3C1=O)OC)c2O)O)(C(=O)CO)O)N)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   543.17 Volume:   516.727
?
Van der Waals volume.
Dense:   1.051 LogP:   1.089
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.614
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.263
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   30.0
TPSA:   206.07
?
Topological Polar Surface Area.
 H-Bond Acceptor:   12.0
H-Bond Donor:   7.0 Rings:   5.0
Heavy Atoms:   12.0

MedChem Properties

QED Drug-Likeness Score:   0.235 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.486 Fsp3:   0.444
MCE-18:   121.154
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Accepted
Pfizer Rule:   Rejected GSK Rule:   Accepted
Golden Triangle Rule:   Accepted BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   1
Colloidal aggregators:   0.564 Fluc inhibitor:   0.021
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.288
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.935
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.009 Promiscuous compounds:   0.968

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.524 MDCK Permeability:   -5.298
Pgp-inhibitor:   0.001 Pgp-substrate:   1.0
PAMPA:   1.0
?
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):   0.979
20% Bioavailability (F20%):   0.982 30% Bioavailability (F30%):   0.999
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.91
Plasma Protein Binding (PPB):   75.882% Volume Distribution (VD):   1.457
Fu: 25.021%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.931
OATP1B3 inhibitor:   0.993 BCRP inhibitor:   0.007
BSEP inhibitor:   0.009

ADMET: Metabolism

CYP1A2-inhibitor:   0.003 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.057 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.002
CYP3A4-inhibitor:   0.002 CYP3A4-substrate:   0.694
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.005
HLM stability:   0.182
?
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):  15.159 Half-life (T1/2):  3.772

ADMET: Toxicity

hERG Blockers:  0.16 hERG Blockers (10um):  0.193
Human Hepatotoxicity (H-HT):  0.988 Drug-induced Liver Injury (DILI):  0.989
AMES Toxicity:  0.983 Rat Oral Acute Toxicity:  0.904
Maximum Recommended Daily Dose:  0.996 Skin Sensitization:  0.998
Carcinogencity:  0.961 Eye Corrosion:  0.0
Eye Irritation:  0.001 Respiratory Toxicity:  0.941
Drug-induced Neurotoxicity:  0.402 Ototoxicity:  0.991
Hematotoxicity:  0.9 Drug-induced Nephrotoxicity:  0.875
Genotoxicity:  0.997 RPMI-8226 Immunitoxicity:  0.817
A549 Cytotoxicity:  0.999 Hek293 Cytotoxicity:  0.895
BCF:   0.546
?
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:   3.319
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.97
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.188
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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
NPO23063 Dryopteris parallelogramma Species Dryopteridaceae 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

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 NPC23467 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 NPC261012
1.0 High Similarity NPC314738
0.9865 High Similarity NPC468994
0.9067 High Similarity NPC109403
0.8947 High Similarity NPC487573
0.8205 Intermediate Similarity NPC603200
0.8125 Intermediate Similarity NPC601855
0.7403 Intermediate Similarity NPC611971
0.6932 Remote Similarity NPC600087
0.6235 Remote Similarity NPC602774
0.5053 Remote Similarity NPC603758

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC23467 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
1.0 High Similarity NPD6781 Phase 4
1.0 High Similarity NPD6782 Phase 4
0.9865 High Similarity NPD6779 Approved
0.9865 High Similarity NPD6780 Approved
0.9067 High Similarity NPD6778 Phase 4
0.8947 High Similarity NPD6777 Approved
0.7816 Intermediate Similarity NPD6776 Approved
0.7403 Intermediate Similarity NPD6535 Phase 4
0.7333 Intermediate Similarity NPD7871 Phase 2
0.7308 Intermediate Similarity NPD6534 Approved
0.7253 Intermediate Similarity NPD7696 Phase 3
0.7253 Intermediate Similarity NPD7697 Phase 3
0.7253 Intermediate Similarity NPD7698 Approved
0.7253 Intermediate Similarity NPD7870 Phase 2
0.7234 Intermediate Similarity NPD7801 Approved
0.7093 Intermediate Similarity NPD7699 Phase 2
0.7093 Intermediate Similarity NPD7700 Phase 2
0.7071 Intermediate Similarity NPD8058 Clinical (unspecified phase)
0.7071 Intermediate Similarity NPD8059 Phase 3
0.6633 Remote Similarity NPD7701 Phase 2
0.6484 Remote Similarity NPD6823 Phase 2
0.6311 Remote Similarity NPD8155 Clinical (unspecified phase)
0.58 Remote Similarity NPD7435 Phase 2
0.566 Remote Similarity NPD7874 Phase 4
0.566 Remote Similarity NPD7875 Clinical (unspecified phase)
0.5135 Remote Similarity NPD7879 Clinical (unspecified phase)

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