Natural Product: NPC79321

Natural Product IDNPC79321
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 UGQMRVRMYYASKQ-PYPIENLJSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 45109804
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000289] Nucleosides, nucleotides, and analogues
      • [CHEMONTID:0000479] Purine nucleosides

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 UGQMRVRMYYASKQ-PYPIENLJSA-N
Standard InCHI InChI=1S/C10H12N4O5/c15-1-4-6(16)7(17)10(19-4)14-3-13-5-8(14)11-2-12-9(5)18/h2-4,6-7,10,15-17H,1H2,(H,11,12,18)/t4?,6?,7?,10-/m1/s1
SMILES C(C1C(C([C@H](n2cnc3c2ncnc3O)O1)O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   268.08 Volume:   233.239
?
Van der Waals volume.
Dense:   1.149 LogP:   -2.021
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   -1.111
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -0.809
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   15.0
TPSA:   133.75
?
Topological Polar Surface Area.
 H-Bond Acceptor:   9.0
H-Bond Donor:   4.0 Rings:   3.0
Heavy Atoms:   9.0

MedChem Properties

QED Drug-Likeness Score:   0.498 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.772 Fsp3:   0.5
MCE-18:   60.067
?
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:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.227 Fluc inhibitor:   0.002
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.023
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.076
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.081 Promiscuous compounds:   0.036

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.091 MDCK Permeability:   -5.191
Pgp-inhibitor:   0.0 Pgp-substrate:   0.2
PAMPA:   0.997
?
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):   0.75
20% Bioavailability (F20%):   0.861 30% Bioavailability (F30%):   0.993
50% Bioavailability (F50%):   0.994

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.002 MRP1:   0.575
Plasma Protein Binding (PPB):   23.329% Volume Distribution (VD):   0.065
Fu: 77.11%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.641
OATP1B3 inhibitor:   0.966 BCRP inhibitor:   0.02
BSEP inhibitor:   0.004

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.127 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.01 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.001
HLM stability:   0.049
?
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):  8.519 Half-life (T1/2):  1.853

ADMET: Toxicity

hERG Blockers:  0.023 hERG Blockers (10um):  0.185
Human Hepatotoxicity (H-HT):  0.678 Drug-induced Liver Injury (DILI):  0.833
AMES Toxicity:  0.63 Rat Oral Acute Toxicity:  0.334
Maximum Recommended Daily Dose:  0.113 Skin Sensitization:  0.311
Carcinogencity:  0.363 Eye Corrosion:  0.0
Eye Irritation:  0.546 Respiratory Toxicity:  0.533
Drug-induced Neurotoxicity:  0.507 Ototoxicity:  0.896
Hematotoxicity:  0.31 Drug-induced Nephrotoxicity:  0.49
Genotoxicity:  0.943 RPMI-8226 Immunitoxicity:  0.102
A549 Cytotoxicity:  0.057 Hek293 Cytotoxicity:  0.315
BCF:   0.079
?
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:   1.831
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   3.377
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   2.344
?
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
NPO25583 Beta vulgaris Species Chenopodiaceae Eukaryota n.a. n.a. n.a. DOI[10.1016/j.procbio.2005.03.071]
NPO25583 Beta vulgaris Species Chenopodiaceae Eukaryota n.a. n.a. n.a. DOI[10.1023/A:1011684619614]
NPO30270 Cordyceps sinensis Species Cordycipitaceae Eukaryota n.a. mycelium n.a. PMID[10423860]
NPO17823 Lycium chinense Species Solanaceae Eukaryota fruits n.a. n.a. PMID[12467621]
NPO2804 Calophyllum inophyllum Species Calophyllaceae Eukaryota n.a. n.a. n.a. PMID[15678383]
NPO30270 Cordyceps sinensis Species Cordycipitaceae Eukaryota n.a. n.a. n.a. PMID[15863936]
NPO2804 Calophyllum inophyllum Species Calophyllaceae Eukaryota n.a. n.a. n.a. PMID[16045947]
NPO17823 Lycium chinense Species Solanaceae Eukaryota n.a. root n.a. PMID[16212233]
NPO2804 Calophyllum inophyllum Species Calophyllaceae Eukaryota n.a. stem n.a. PMID[20188156]
NPO30270 Cordyceps sinensis Species Cordycipitaceae Eukaryota n.a. n.a. n.a. PMID[21848266]
NPO30270 Cordyceps sinensis Species Cordycipitaceae Eukaryota n.a. mycelium n.a. PMID[21848266]
NPO17823 Lycium chinense Species Solanaceae Eukaryota root bark n.a. n.a. PMID[23282106]
NPO17823 Lycium chinense Species Solanaceae Eukaryota Root Bark n.a. n.a. PMID[26982999]
NPO25583 Beta vulgaris Species Chenopodiaceae Eukaryota n.a. n.a. n.a. PMID[33118348]
NPO25583 Beta vulgaris Species Chenopodiaceae Eukaryota n.a. n.a. n.a. PMID[36432211]
NPO2804 Calophyllum inophyllum Species Calophyllaceae Eukaryota n.a. Malaysian n.a. PMID[7506311]
NPO17823 Lycium chinense Species Solanaceae Eukaryota fruits n.a. n.a. PMID[9090870]
NPO25583 Beta vulgaris Species Chenopodiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17823 Lycium chinense Species Solanaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2804 Calophyllum inophyllum Species Calophyllaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27451 Ophiocordyceps sinensis Species Ophiocordycipitaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24062 Radix pseudostellariae Species Lymnaeidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO30270 Cordyceps sinensis Species Cordycipitaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28126 Cordyceps militaris Species Cordycipitaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25583 Beta vulgaris Species Chenopodiaceae Eukaryota Root n.a. n.a. Database[FooDB]
NPO25583 Beta vulgaris Species Chenopodiaceae Eukaryota Leaf n.a. n.a. Database[FooDB]
NPO25583 Beta vulgaris Species Chenopodiaceae Eukaryota n.a. n.a. Database[FooDB]
NPO30270 Cordyceps sinensis Species Cordycipitaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO28126 Cordyceps militaris Species Cordycipitaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO2804 Calophyllum inophyllum Species Calophyllaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO25583 Beta vulgaris Species Chenopodiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO17823 Lycium chinense Species Solanaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO17823 Lycium chinense Species Solanaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO26036 Cordyceps militaris cv Species Cordycipitaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO24062 Radix pseudostellariae Species Lymnaeidae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO25583 Beta vulgaris Species Chenopodiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO2804 Calophyllum inophyllum Species Calophyllaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO27451 Ophiocordyceps sinensis Species Ophiocordycipitaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO28126 Cordyceps militaris Species Cordycipitaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO25583 Beta vulgaris Species Chenopodiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO30270 Cordyceps sinensis Species Cordycipitaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO17823 Lycium chinense Species Solanaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO17823 Lycium chinense Species Solanaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO27451 Ophiocordyceps sinensis Species Ophiocordycipitaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO2804 Calophyllum inophyllum Species Calophyllaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28126 Cordyceps militaris Species Cordycipitaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25583 Beta vulgaris Species Chenopodiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17823 Lycium chinense Species Solanaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27451 Ophiocordyceps sinensis Species Ophiocordycipitaceae 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 NPC79321 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 NPC54320
0.7069 Intermediate Similarity NPC261595
0.6852 Remote Similarity NPC52238
0.6852 Remote Similarity NPC311197
0.6508 Remote Similarity NPC324033
0.625 Remote Similarity NPC156461
0.625 Remote Similarity NPC107374
0.625 Remote Similarity NPC600382
0.625 Remote Similarity NPC612067
0.6212 Remote Similarity NPC321458
0.6182 Remote Similarity NPC207633
0.6071 Remote Similarity NPC485738
0.5862 Remote Similarity NPC608634
0.5857 Remote Similarity NPC484200
0.5775 Remote Similarity NPC484197
0.5614 Remote Similarity NPC320818
0.5538 Remote Similarity NPC239737
0.55 Remote Similarity NPC164665
0.5333 Remote Similarity NPC609036
0.5161 Remote Similarity NPC269827
0.5161 Remote Similarity NPC189068
0.5085 Remote Similarity NPC317821
0.507 Remote Similarity NPC250178

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC79321 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 NPD219 Phase 4
1.0 High Similarity NPD220 Clinical (unspecified phase)
0.8491 Intermediate Similarity NPD216 Approved
0.7069 Intermediate Similarity NPD247 Clinical (unspecified phase)
0.6364 Remote Similarity NPD213 Clinical (unspecified phase)
0.6364 Remote Similarity NPD214 Phase 4
0.625 Remote Similarity NPD249 Phase 4
0.625 Remote Similarity NPD250 Phase 4
0.6164 Remote Similarity NPD217 Approved
0.6164 Remote Similarity NPD218 Approved
0.5161 Remote Similarity NPD195 Approved
0.5147 Remote Similarity NPD1369 Phase 2
0.5147 Remote Similarity NPD1750 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