Natural Product: NPC177228

Natural Product IDNPC177228
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 YYEFTOIQHQHUQZ-BDTNDASRSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 10645351
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0000337] Flavans
          • [CHEMONTID:0003012] Flavan-3-ols
            • [CHEMONTID:0001584] Catechins

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 YYEFTOIQHQHUQZ-BDTNDASRSA-N
Standard InCHI InChI=1S/C22H20O6S/c23-14-9-17(26)19-18(10-14)28-21(13-6-7-15(24)16(25)8-13)20(27)22(19)29-11-12-4-2-1-3-5-12/h1-10,20-27H,11H2/t20-,21+,22-/m0/s1
SMILES c1ccc(cc1)CS[C@H]1c2c(cc(cc2O[C@H](c2ccc(c(c2)O)O)[C@@H]1O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   412.1 Volume:   402.365
?
Van der Waals volume.
Dense:   1.024 LogP:   1.965
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.191
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.377
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   23.0
TPSA:   110.38
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   5.0 Rings:   4.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.412 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.685 Fsp3:   0.182
MCE-18:   74.308
?
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:   1 PAINS Alert:   1
Colloidal aggregators:   0.848 Fluc inhibitor:   0.445
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.145
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.432
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.481 Promiscuous compounds:   0.149

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.762 MDCK Permeability:   -5.003
Pgp-inhibitor:   0.309 Pgp-substrate:   0.007
PAMPA:   0.021
?
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):   0.005
20% Bioavailability (F20%):   0.106 30% Bioavailability (F30%):   0.997
50% Bioavailability (F50%):   0.929

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.061 MRP1:   0.623
Plasma Protein Binding (PPB):   98.56% Volume Distribution (VD):   -0.099
Fu: 1.313%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.993
OATP1B3 inhibitor:   0.985 BCRP inhibitor:   0.056
BSEP inhibitor:   0.581

ADMET: Metabolism

CYP1A2-inhibitor:   0.027 CYP1A2-substrate:   0.003
CYP2C19-inhibitor:   0.001 CYP2C19-substrate:   0.039
CYP2C9-inhibitor:   0.003 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.061
CYP3A4-inhibitor:   0.132 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.999
HLM stability:   0.013
?
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):  13.307 Half-life (T1/2):  1.79

ADMET: Toxicity

hERG Blockers:  0.119 hERG Blockers (10um):  0.731
Human Hepatotoxicity (H-HT):  0.279 Drug-induced Liver Injury (DILI):  0.849
AMES Toxicity:  0.564 Rat Oral Acute Toxicity:  0.186
Maximum Recommended Daily Dose:  0.579 Skin Sensitization:  1.0
Carcinogencity:  0.053 Eye Corrosion:  0.056
Eye Irritation:  0.987 Respiratory Toxicity:  0.946
Drug-induced Neurotoxicity:  0.045 Ototoxicity:  0.273
Hematotoxicity:  0.04 Drug-induced Nephrotoxicity:  0.136
Genotoxicity:  0.697 RPMI-8226 Immunitoxicity:  0.042
A549 Cytotoxicity:  0.828 Hek293 Cytotoxicity:  0.672
BCF:   1.278
?
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:   4.248
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.26
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.975
?
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
NPO12068 Firmiana simplex Species Malvaceae Eukaryota n.a. n.a. n.a. PMID[16124753]
NPO2669 Bowdichia virgilioides Species Fabaceae Eukaryota n.a. xylem n.a. PMID[16286304]
NPO2669 Bowdichia virgilioides Species Fabaceae Eukaryota Seeds n.a. n.a. PMID[29182338]
NPO8443 Uvaria microcarpa Species Annonaceae Eukaryota n.a. n.a. n.a. PMID[37531297]
NPO6937 Xylaria hypoxylon Species Xylariaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4844 Acacia simplicifolia Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2669 Bowdichia virgilioides Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1406 Centaurea zuccariniana Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8962 Cousinia canescens Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12068 Firmiana simplex Species Malvaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8140 Nauclea parva Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5752 Pholas dactylus Species Pholadidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5365 Tetradenia glauca Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9947 Teucrium scorodonia Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2905 Tinospora hainanensis Species Menispermaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21689 Titanotrichum oldhamii Species Gesneriaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8443 Uvaria microcarpa Species Annonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4037 Veronica anagallis Species Plantaginaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1255 Waitzia acuminata Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3463 Wrightia tinctoria Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2905 Tinospora hainanensis Species Menispermaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO12068 Firmiana simplex Species Malvaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO12068 Firmiana simplex Species Malvaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO9947 Teucrium scorodonia Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO8635 Sapindus delavayi Species Sapindaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO2905 Tinospora hainanensis Species Menispermaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO12068 Firmiana simplex Species Malvaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO5365 Tetradenia glauca Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9947 Teucrium scorodonia Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21689 Titanotrichum oldhamii Species Gesneriaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2905 Tinospora hainanensis Species Menispermaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11526 Vismia latifolia Species Hypericaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3463 Wrightia tinctoria Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12068 Firmiana simplex Species Malvaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4844 Acacia simplicifolia Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2669 Bowdichia virgilioides Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8443 Uvaria microcarpa Species Annonaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8140 Nauclea parva Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6010 Haeckeria punctulata Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6937 Xylaria hypoxylon Species Xylariaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8635 Sapindus delavayi Species Sapindaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1406 Centaurea zuccariniana Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8962 Cousinia canescens Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1255 Waitzia acuminata Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5752 Pholas dactylus Species Pholadidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23956 Trichoderma deliquescens Species Hypocreaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4037 Veronica anagallis Species Plantaginaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28393 Urospora penicilliformis Species Ulotrichaceae 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 NPC177228 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
0.6721 Remote Similarity NPC150670
0.5833 Remote Similarity NPC261619
0.5833 Remote Similarity NPC61477
0.5833 Remote Similarity NPC78770
0.5833 Remote Similarity NPC219876
0.5833 Remote Similarity NPC126029
0.5833 Remote Similarity NPC15658
0.5312 Remote Similarity NPC36835
0.5312 Remote Similarity NPC246162
0.5312 Remote Similarity NPC9743
0.5312 Remote Similarity NPC260491
0.5312 Remote Similarity NPC61506
0.5312 Remote Similarity NPC240476
0.5152 Remote Similarity NPC178054

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC177228 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
0.5833 Remote Similarity NPD1612 Clinical (unspecified phase)
0.5833 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