Natural Product: NPC602382

Natural Product IDNPC602382
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 CMGRMMSVGCHWOK-FQRUVTKNSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL349707
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 CMGRMMSVGCHWOK-FQRUVTKNSA-N
Standard InCHI InChI=1S/C27H20O13/c28-12-6-14(29)13-8-20(40-27(38)11-4-15(30)22(34)16(31)5-11)26(39-19(13)7-12)10-1-9-2-18(33)24(36)25(37)21(9)23(35)17(32)3-10/h1-7,20,26,28-31,33-34,36-37H,8H2,(H,32,35)/t20-,26-/m1/s1
SMILES O=C(O[C@@H]1Cc2c(O)cc(O)cc2O[C@@H]1c1cc(O)c(=O)c2c(O)c(O)c(O)cc2c1)c1cc(O)c(O)c(O)c1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   552.09 Volume:   512.765
?
Van der Waals volume.
Dense:   1.077 LogP:   1.42
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.403
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.191
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   31.0
TPSA:   234.67
?
Topological Polar Surface Area.
 H-Bond Acceptor:   13.0
H-Bond Donor:   9.0 Rings:   5.0
Heavy Atoms:   13.0

MedChem Properties

QED Drug-Likeness Score:   0.131 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.071 Fsp3:   0.111
MCE-18:   108.8
?
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:   1
Chelating Alert:   1 PAINS Alert:   1
Colloidal aggregators:   0.992 Fluc inhibitor:   0.293
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.755
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.655
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.682 Promiscuous compounds:   0.828

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -7.141 MDCK Permeability:   -4.842
Pgp-inhibitor:   0.0 Pgp-substrate:   0.013
PAMPA:   0.985
?
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):   0.007
20% Bioavailability (F20%):   0.999 30% Bioavailability (F30%):   1.0
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   1.0
Plasma Protein Binding (PPB):   89.87% Volume Distribution (VD):   -0.289
Fu: 10.973%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.993
OATP1B3 inhibitor:   0.985 BCRP inhibitor:   0.644
BSEP inhibitor:   0.002

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.001
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.987
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.94
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.999
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.064
?
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):  5.118 Half-life (T1/2):  2.773

ADMET: Toxicity

hERG Blockers:  0.048 hERG Blockers (10um):  0.934
Human Hepatotoxicity (H-HT):  0.312 Drug-induced Liver Injury (DILI):  0.964
AMES Toxicity:  0.887 Rat Oral Acute Toxicity:  0.552
Maximum Recommended Daily Dose:  0.957 Skin Sensitization:  1.0
Carcinogencity:  0.266 Eye Corrosion:  0.0
Eye Irritation:  0.987 Respiratory Toxicity:  0.879
Drug-induced Neurotoxicity:  0.001 Ototoxicity:  0.951
Hematotoxicity:  0.004 Drug-induced Nephrotoxicity:  0.007
Genotoxicity:  1.0 RPMI-8226 Immunitoxicity:  0.006
A549 Cytotoxicity:  1.0 Hek293 Cytotoxicity:  0.849
BCF:   0.754
?
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:   3.541
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.436
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.111
?
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
NPO8258 Camellia sinensis Species Theaceae Eukaryota n.a. n.a. n.a. PMID[ 16712885]
NPO8258 Camellia sinensis Species Theaceae Eukaryota n.a. n.a. n.a. DOI[10.1016/j.foodchem.2013.08.121]
NPO8258 Camellia sinensis Species Theaceae Eukaryota Flowers n.a. n.a. PMID[16180814]
NPO8258 Camellia sinensis Species Theaceae Eukaryota seeds Shizuoka prefecture, Japan n.a. PMID[16499314]
NPO8258 Camellia sinensis Species Theaceae Eukaryota n.a. n.a. n.a. PMID[18068204]
NPO8258 Camellia sinensis Species Theaceae Eukaryota n.a. n.a. n.a. PMID[21434603]
NPO8258 Camellia sinensis Species Theaceae Eukaryota n.a. flower n.a. PMID[21922925]
NPO8258 Camellia sinensis Species Theaceae Eukaryota flower buds n.a. n.a. PMID[21925888]
NPO8258 Camellia sinensis Species Theaceae Eukaryota leaves n.a. n.a. PMID[22377672]
NPO8258 Camellia sinensis Species Theaceae Eukaryota n.a. leaf n.a. PMID[23265489]
NPO8258 Camellia sinensis Species Theaceae Eukaryota Leaves Bandung, West Java, Indonesia PMID[23621359]
NPO8258 Camellia sinensis Species Theaceae Eukaryota n.a. n.a. n.a. PMID[37255739]
NPO8258 Camellia sinensis Species Theaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8258 Camellia sinensis Species Theaceae Eukaryota n.a. n.a. Database[FooDB]
NPO8258 Camellia sinensis Species Theaceae Eukaryota n.a. n.a. Database[FooDB]
NPO8258 Camellia sinensis Species Theaceae Eukaryota Stem n.a. n.a. Database[FooDB]
NPO8258 Camellia sinensis Species Theaceae Eukaryota Shoot n.a. n.a. Database[FooDB]
NPO8258 Camellia sinensis Species Theaceae Eukaryota Seed Oil n.a. n.a. Database[FooDB]
NPO8258 Camellia sinensis Species Theaceae Eukaryota Seed n.a. n.a. Database[FooDB]
NPO8258 Camellia sinensis Species Theaceae Eukaryota Plant n.a. n.a. Database[FooDB]
NPO8258 Camellia sinensis Species Theaceae Eukaryota Leaf Essent. Oil n.a. n.a. Database[FooDB]
NPO8258 Camellia sinensis Species Theaceae Eukaryota Leaf n.a. n.a. Database[FooDB]
NPO8258 Camellia sinensis Species Theaceae Eukaryota Cotyledon n.a. n.a. Database[FooDB]
NPO8258 Camellia sinensis Species Theaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO8258 Camellia sinensis Species Theaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO8258 Camellia sinensis Species Theaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO8258 Camellia sinensis Species Theaceae 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
NPT759 Cell line H9 Homo sapiens IC50 = 25.0 ug.mL-1 DOI[10.1016/0960-894X(96)00095-9]
NPT28438 Unchecked Unchecked n.a. IC50 = 11000.0 nM PMID[37776575]
NPT24 Organism Human immunodeficiency virus 1 Human immunodeficiency virus 1 EC50 = 5.5 ug.mL-1 DOI[10.1016/0960-894X(96)00095-9]

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 NPC602382 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
0.7703 Intermediate Similarity NPC602962
0.7037 Intermediate Similarity NPC600812
0.697 Remote Similarity NPC291948
0.697 Remote Similarity NPC104983
0.697 Remote Similarity NPC250436
0.697 Remote Similarity NPC300845
0.697 Remote Similarity NPC88803
0.6479 Remote Similarity NPC38779
0.6479 Remote Similarity NPC114179
0.6479 Remote Similarity NPC68324
0.6479 Remote Similarity NPC289322
0.6479 Remote Similarity NPC156818
0.6479 Remote Similarity NPC160512
0.6316 Remote Similarity NPC603291
0.6267 Remote Similarity NPC603842
0.6133 Remote Similarity NPC87317
0.5584 Remote Similarity NPC601196
0.5432 Remote Similarity NPC100251
0.5395 Remote Similarity NPC474656
0.5375 Remote Similarity NPC53889
0.5238 Remote Similarity NPC65333
0.5116 Remote Similarity NPC98583

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC602382 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
0.697 Remote Similarity NPD4868 Phase 3
0.573 Remote Similarity NPD7993 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