Natural Product: NPC601196

Natural Product IDNPC601196
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 BXDRTHBTGNNTEW-NHCUHLMSSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL159433
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 BXDRTHBTGNNTEW-NHCUHLMSSA-N
Standard InCHI InChI=1S/C23H20O10/c1-31-22-17(28)5-11(6-18(22)29)23(30)33-20-9-13-15(26)7-12(24)8-19(13)32-21(20)10-2-3-14(25)16(27)4-10/h2-8,20-21,24-29H,9H2,1H3/t20-,21-/m1/s1
SMILES COc1c(O)cc(C(=O)O[C@@H]2Cc3c(O)cc(O)cc3O[C@@H]2c2ccc(O)c(O)c2)cc1O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   456.11 Volume:   433.676
?
Van der Waals volume.
Dense:   1.052 LogP:   2.03
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.152
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.725
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   24.0
TPSA:   166.14
?
Topological Polar Surface Area.
 H-Bond Acceptor:   10.0
H-Bond Donor:   6.0 Rings:   4.0
Heavy Atoms:   10.0

MedChem Properties

QED Drug-Likeness Score:   0.254 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.63 Fsp3:   0.174
MCE-18:   83.778
?
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:   1
Chelating Alert:   1 PAINS Alert:   1
Colloidal aggregators:   0.85 Fluc inhibitor:   0.429
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.35
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.763
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.551 Promiscuous compounds:   0.691

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.219 MDCK Permeability:   -5.021
Pgp-inhibitor:   0.025 Pgp-substrate:   0.065
PAMPA:   0.061
?
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):   0.0
20% Bioavailability (F20%):   0.965 30% Bioavailability (F30%):   0.985
50% Bioavailability (F50%):   0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.032 MRP1:   0.997
Plasma Protein Binding (PPB):   94.044% Volume Distribution (VD):   -0.384
Fu: 6.708%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.987
OATP1B3 inhibitor:   0.976 BCRP inhibitor:   0.35
BSEP inhibitor:   0.088

ADMET: Metabolism

CYP1A2-inhibitor:   0.001 CYP1A2-substrate:   0.027
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.278
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.028
CYP3A4-inhibitor:   0.198 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.03
?
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):  6.966 Half-life (T1/2):  1.995

ADMET: Toxicity

hERG Blockers:  0.074 hERG Blockers (10um):  0.795
Human Hepatotoxicity (H-HT):  0.304 Drug-induced Liver Injury (DILI):  0.792
AMES Toxicity:  0.699 Rat Oral Acute Toxicity:  0.639
Maximum Recommended Daily Dose:  0.776 Skin Sensitization:  0.997
Carcinogencity:  0.431 Eye Corrosion:  0.012
Eye Irritation:  0.987 Respiratory Toxicity:  0.847
Drug-induced Neurotoxicity:  0.093 Ototoxicity:  0.384
Hematotoxicity:  0.026 Drug-induced Nephrotoxicity:  0.057
Genotoxicity:  0.981 RPMI-8226 Immunitoxicity:  0.064
A549 Cytotoxicity:  0.981 Hek293 Cytotoxicity:  0.85
BCF:   0.89
?
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:   3.501
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.803
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.17
?
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]
NPO8258.1 Camellia sinensis var. assamica Varieties Theaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
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]
NPO8258.1 Camellia sinensis var. assamica Varieties Theaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO8258 Camellia sinensis Species Theaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO8258.1 Camellia sinensis var. assamica Varieties Theaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
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
NPT4015 Individual protein Matrix metalloproteinase 14 Homo sapiens IC50 = 3700.0 nM PMID[19524436]
NPT4016 Individual protein Matrix metalloproteinase 7 Homo sapiens IC50 > 100000.0 nM PMID[19524436]
NPT568 Individual protein Matrix metalloproteinase-2 Homo sapiens IC50 = 34000.0 nM PMID[19524436]

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 = 50.0 ug.mL-1 DOI[10.1016/0960-894X(96)00095-9]
NPT24 Organism Human immunodeficiency virus 1 Human immunodeficiency virus 1 EC50 n.a. n.a. 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 NPC601196 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
0.8136 Intermediate Similarity NPC38779
0.8136 Intermediate Similarity NPC114179
0.8136 Intermediate Similarity NPC68324
0.8136 Intermediate Similarity NPC289322
0.8136 Intermediate Similarity NPC160512
0.7833 Intermediate Similarity NPC474656
0.7656 Intermediate Similarity NPC53889
0.7258 Intermediate Similarity NPC156818
0.7 Intermediate Similarity NPC291948
0.7 Intermediate Similarity NPC104983
0.7 Intermediate Similarity NPC250436
0.7 Intermediate Similarity NPC300845
0.7 Intermediate Similarity NPC88803
0.6716 Remote Similarity NPC603842
0.6438 Remote Similarity NPC98583
0.6324 Remote Similarity NPC87317
0.5833 Remote Similarity NPC603291
0.5584 Remote Similarity NPC602382
0.5541 Remote Similarity NPC100251
0.5417 Remote Similarity NPC40222
0.5417 Remote Similarity NPC268515
0.5316 Remote Similarity NPC602962
0.525 Remote Similarity NPC135021
0.5156 Remote Similarity NPC261619
0.5156 Remote Similarity NPC61477
0.5156 Remote Similarity NPC78770
0.5156 Remote Similarity NPC219876
0.5156 Remote Similarity NPC126029
0.5156 Remote Similarity NPC15658
0.5128 Remote Similarity NPC65333
0.5128 Remote Similarity NPC278548

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC601196 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
0.7 Intermediate Similarity NPD4868 Phase 3
0.5156 Remote Similarity NPD1612 Clinical (unspecified phase)
0.5156 Remote Similarity NPD1613 Phase 4

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