Natural Product: NPC276822

Natural Product IDNPC276822
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 NCDIBOQDVNONGL-HISJFFBUSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL3102874
PubChem CID 10410865
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0002389] Diazinanes
        • [CHEMONTID:0000189] Piperazines
          • [CHEMONTID:0001731] Dioxopiperazines
            • [CHEMONTID:0003684] 2,5-dioxopiperazines
              • [CHEMONTID:0001732] Thiodioxopiperazines
                • [CHEMONTID:0001790] Epipolythiodioxopiperazines

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 NCDIBOQDVNONGL-HISJFFBUSA-N
Standard InCHI InChI=1S/C18H18N2O7S2/c21-8-1-2-9(22)12-6(8)4-17-16(27)20-13-7(10(23)3-11(24)14(13)25)5-18(20,29-28-17)15(26)19(12)17/h1-2,6-7,9,11-14,22,24-25H,3-5H2/t6-,7+,9+,11+,12+,13+,14+,17-,18-/m1/s1
SMILES C1=C[C@@H]([C@@H]2[C@H](C[C@@]34C(=O)N5[C@H]6[C@@H](C[C@]5(C(=O)N23)SS4)C(=O)C[C@@H]([C@@H]6O)O)C1=O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   438.06 Volume:   375.906
?
Van der Waals volume.
Dense:   1.165 LogP:   -0.757
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   0.124
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -1.381
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   0.0 Rigid Bonds:   31.0
TPSA:   135.45
?
Topological Polar Surface Area.
 H-Bond Acceptor:   9.0
H-Bond Donor:   3.0 Rings:   7.0
Heavy Atoms:   11.0

MedChem Properties

QED Drug-Likeness Score:   0.383 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   6.93 Fsp3:   0.667
MCE-18:   140.6
?
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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.869 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.12
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.014
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.751 Promiscuous compounds:   0.222

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.842 MDCK Permeability:   -5.185
Pgp-inhibitor:   0.001 Pgp-substrate:   0.154
PAMPA:   0.995
?
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):   0.331
20% Bioavailability (F20%):   0.588 30% Bioavailability (F30%):   0.849
50% Bioavailability (F50%):   0.96

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.047 MRP1:   0.618
Plasma Protein Binding (PPB):   43.09% Volume Distribution (VD):   -0.201
Fu: 57.051%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.298
OATP1B3 inhibitor:   0.516 BCRP inhibitor:   0.001
BSEP inhibitor:   0.301

ADMET: Metabolism

CYP1A2-inhibitor:   0.001 CYP1A2-substrate:   0.017
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.006
CYP2C9-inhibitor:   0.063 CYP2C9-substrate:   0.005
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.001
CYP3A4-inhibitor:   0.004 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.986
HLM stability:   0.653
?
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):  3.476 Half-life (T1/2):  2.247

ADMET: Toxicity

hERG Blockers:  0.06 hERG Blockers (10um):  0.099
Human Hepatotoxicity (H-HT):  0.431 Drug-induced Liver Injury (DILI):  0.997
AMES Toxicity:  0.409 Rat Oral Acute Toxicity:  0.78
Maximum Recommended Daily Dose:  0.204 Skin Sensitization:  1.0
Carcinogencity:  0.081 Eye Corrosion:  0.0
Eye Irritation:  0.26 Respiratory Toxicity:  0.871
Drug-induced Neurotoxicity:  0.032 Ototoxicity:  0.047
Hematotoxicity:  0.958 Drug-induced Nephrotoxicity:  0.976
Genotoxicity:  1.0 RPMI-8226 Immunitoxicity:  0.725
A549 Cytotoxicity:  0.033 Hek293 Cytotoxicity:  0.361
BCF:   0.797
?
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:   5.151
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.736
?
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
NPO21301 Stereum hirsutum Species Stereaceae Eukaryota n.a. n.a. n.a. PMID[12003003]
NPO21558 Ormosia sumatrana Species Fabaceae Eukaryota leaves n.a. n.a. PMID[15568789]
NPO19990 Axinyssa isabela Species Halichondriidae Eukaryota n.a. Isla Isabel (Gulf of California, Mexico) n.a. PMID[19007287]
NPO9838 Eucalyptus maideni Species Myrtaceae Eukaryota fresh leaves n.a. n.a. PMID[19778089]
NPO9838 Eucalyptus maideni Species Myrtaceae Eukaryota fresh fruits n.a. n.a. PMID[20092288]
NPO33508 Phoma sp. OUCMDZ-1847 Species Didymellaceae Eukaryota n.a. n.a. n.a. PMID[24370114]
NPO1493 Hericium erinaceus Species Hericiaceae Eukaryota n.a. n.a. n.a. PMID[25565282]
NPO1493 Hericium erinaceus Species Hericiaceae Eukaryota Mycelia n.a. n.a. PMID[26807743]
NPO1493 Hericium erinaceus Species Hericiaceae Eukaryota Fruiting Bodies n.a. n.a. PMID[33246107]
NPO19796 Azolla filiculoides Species Azollaceae Eukaryota n.a. n.a. n.a. PMID[37765393]
NPO4994 Pachysandra procumbens Species Buxaceae Eukaryota n.a. n.a. n.a. PMID[9784163]
NPO21238 Berberis tabiensis Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20276 Burasaia madagascariensis Species Menispermaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19796 Azolla filiculoides Species Azollaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19990 Axinyssa isabela Species Halichondriidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24508 Aspergillus brunneus Species Aspergillaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17541 Andryala pinnatifida Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9838 Eucalyptus maideni Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1493 Hericium erinaceus Species Hericiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20485 Cussonia arborea Species Araliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18460 Trema dielsiana Species Cannabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19031 Thymus marschallianus Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20747 Stictocardia campanulata Species Convolvulaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21301 Stereum hirsutum Species Stereaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21431 Rapanea laetevirens Species Primulaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18857 Pteronia eenii Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13404 Plantago subulata Species Plantaginaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4994 Pachysandra procumbens Species Buxaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21558 Ormosia sumatrana Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21490 Hypoxylon fragiforme Species Xylariaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19907 Helicobasidium mompa Species Helicobasidiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18114 Cyclamen repandum Species Primulaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1493 Hericium erinaceus Species Hericiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO18460 Trema dielsiana Species Cannabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO21301 Stereum hirsutum Species Stereaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO1493 Hericium erinaceus Species Hericiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO18460 Trema dielsiana Species Cannabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO1493 Hericium erinaceus Species Hericiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO21490 Hypoxylon fragiforme Species Xylariaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24508 Aspergillus brunneus Species Aspergillaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19990 Axinyssa isabela Species Halichondriidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21558 Ormosia sumatrana Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17541 Andryala pinnatifida Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9838 Eucalyptus maideni Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13404 Plantago subulata Species Plantaginaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21238 Berberis tabiensis Species Berberidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19796 Azolla filiculoides Species Azollaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19907 Helicobasidium mompa Species Helicobasidiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18114 Cyclamen repandum Species Primulaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19031 Thymus marschallianus Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1493 Hericium erinaceus Species Hericiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4994 Pachysandra procumbens Species Buxaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21431 Rapanea laetevirens Species Primulaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21301 Stereum hirsutum Species Stereaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18857 Pteronia eenii Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20485 Cussonia arborea Species Araliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20276 Burasaia madagascariensis Species Menispermaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18460 Trema dielsiana Species Cannabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20747 Stictocardia campanulata Species Convolvulaceae 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
NPT3140 Cell line MGC-803 Homo sapiens IC50 = 3400.0 nM PMID[24370114]
NPT111 Cell line K562 Homo sapiens IC50 > 10000.0 nM PMID[24370114]
NPT81 Cell line A549 Homo sapiens IC50 > 10000.0 nM PMID[24370114]
NPT393 Cell line HCT-116 Homo sapiens IC50 = 7100.0 nM PMID[24370114]
NPT116 Cell line HL-60 Homo sapiens IC50 = 3500.0 nM PMID[24370114]

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 NPC276822 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
0.7727 Intermediate Similarity NPC262880
0.7727 Intermediate Similarity NPC247902
0.7551 Intermediate Similarity NPC485902
0.75 Intermediate Similarity NPC266910
0.7143 Intermediate Similarity NPC485905
0.7059 Intermediate Similarity NPC485901
0.6545 Remote Similarity NPC485900
0.6182 Remote Similarity NPC485903
0.5469 Remote Similarity NPC483103
0.5306 Remote Similarity NPC485904

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC276822 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
NPD

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