Natural Product: NPC104060

Natural Product IDNPC104060
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 YKGCBLWILMDSAV-UHFFFAOYSA-M
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 25200491
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0000337] Flavans
          • [CHEMONTID:0003642] 8-prenylated flavans
            • [CHEMONTID:0003508] 8-prenylated flavanones

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 YKGCBLWILMDSAV-UHFFFAOYSA-M
Standard InCHI InChI=1S/C21H22O5/c1-12(2)4-9-15-16(23)10-19(25-3)20-17(24)11-18(26-21(15)20)13-5-7-14(22)8-6-13/h4-8,10,18,22-23H,9,11H2,1-3H3/p-1
SMILES CC(=CCc1c(cc(c2C(=O)CC(c3ccc(cc3)[O-])Oc12)OC)O)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   354.15 Volume:   368.962
?
Van der Waals volume.
Dense:   0.96 LogP:   3.487
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.244
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.49
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   19.0
TPSA:   75.99
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   2.0 Rings:   3.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.8 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.16 Fsp3:   0.286
MCE-18:   59.815
?
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:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.714 Fluc inhibitor:   0.275
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.735
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.513
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.289 Promiscuous compounds:   0.022

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.826 MDCK Permeability:   -4.738
Pgp-inhibitor:   0.968 Pgp-substrate:   0.044
PAMPA:   0.06
?
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):   0.025
20% Bioavailability (F20%):   0.494 30% Bioavailability (F30%):   0.993
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.904
Plasma Protein Binding (PPB):   94.823% Volume Distribution (VD):   0.253
Fu: 4.546%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.983
OATP1B3 inhibitor:   0.998 BCRP inhibitor:   0.999
BSEP inhibitor:   0.968

ADMET: Metabolism

CYP1A2-inhibitor:   0.085 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   1.0
CYP2C9-inhibitor:   0.159 CYP2C9-substrate:   0.181
CYP2D6-inhibitor:   0.932 CYP2D6-substrate:   0.987
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   1.0
?
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):  5.659 Half-life (T1/2):  1.171

ADMET: Toxicity

hERG Blockers:  0.149 hERG Blockers (10um):  0.598
Human Hepatotoxicity (H-HT):  0.765 Drug-induced Liver Injury (DILI):  0.417
AMES Toxicity:  0.685 Rat Oral Acute Toxicity:  0.747
Maximum Recommended Daily Dose:  0.592 Skin Sensitization:  0.888
Carcinogencity:  0.632 Eye Corrosion:  0.0
Eye Irritation:  0.78 Respiratory Toxicity:  0.794
Drug-induced Neurotoxicity:  0.672 Ototoxicity:  0.497
Hematotoxicity:  0.292 Drug-induced Nephrotoxicity:  0.72
Genotoxicity:  0.918 RPMI-8226 Immunitoxicity:  0.084
A549 Cytotoxicity:  0.345 Hek293 Cytotoxicity:  0.794
BCF:   1.65
?
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:   4.523
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.808
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.298
?
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
NPO13661 Tripterygium wilfordii Species Celastraceae Eukaryota n.a. n.a. n.a. DOI[10.1016/0031-9422(90)85349-K]
NPO13661 Tripterygium wilfordii Species Celastraceae Eukaryota n.a. root n.a. DOI[10.1186/1471-2202-6-1]
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. cone n.a. PMID[10336650]
NPO13661 Tripterygium wilfordii Species Celastraceae Eukaryota n.a. n.a. n.a. PMID[10579865]
NPO19231 Sophora flavescens Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[10654410]
NPO13661 Tripterygium wilfordii Species Celastraceae Eukaryota n.a. leaf n.a. PMID[10716597]
NPO13661 Tripterygium wilfordii Species Celastraceae Eukaryota n.a. n.a. n.a. PMID[10757718]
NPO19231 Sophora flavescens Species Fabaceae Eukaryota n.a. root n.a. PMID[10843587]
NPO13661 Tripterygium wilfordii Species Celastraceae Eukaryota n.a. n.a. n.a. PMID[11374948]
NPO13661 Tripterygium wilfordii Species Celastraceae Eukaryota n.a. n.a. n.a. PMID[11561442]
NPO13661 Tripterygium wilfordii Species Celastraceae Eukaryota n.a. n.a. n.a. PMID[12579877]
NPO13661 Tripterygium wilfordii Species Celastraceae Eukaryota n.a. n.a. n.a. PMID[1375626]
NPO13661 Tripterygium wilfordii Species Celastraceae Eukaryota n.a. root n.a. PMID[1375626]
NPO19231 Sophora flavescens Species Fabaceae Eukaryota Roots n.a. n.a. PMID[15568770]
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. n.a. n.a. PMID[15679315]
NPO13661 Tripterygium wilfordii Species Celastraceae Eukaryota n.a. root n.a. PMID[1602302]
NPO13661 Tripterygium wilfordii Species Celastraceae Eukaryota n.a. n.a. n.a. PMID[1602302]
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. n.a. n.a. PMID[16252923]
NPO19231 Sophora flavescens Species Fabaceae Eukaryota n.a. root n.a. PMID[16392664]
NPO13661 Tripterygium wilfordii Species Celastraceae Eukaryota n.a. root n.a. PMID[16864458]
NPO19231 Sophora flavescens Species Fabaceae Eukaryota roots Hualien Hsien, Taiwan 2003-JUL PMID[16933887]
NPO19231 Sophora flavescens Species Fabaceae Eukaryota n.a. root n.a. PMID[16933887]
NPO13661 Tripterygium wilfordii Species Celastraceae Eukaryota roots n.a. n.a. PMID[16989518]
NPO13661 Tripterygium wilfordii Species Celastraceae Eukaryota n.a. root n.a. PMID[17250858]
NPO13661 Tripterygium wilfordii Species Celastraceae Eukaryota n.a. n.a. n.a. PMID[17265278]
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. cone n.a. PMID[17624889]
NPO19231 Sophora flavescens Species Fabaceae Eukaryota n.a. root n.a. PMID[17951038]
NPO19231 Sophora flavescens Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[18175961]
NPO13661 Tripterygium wilfordii Species Celastraceae Eukaryota n.a. root n.a. PMID[1823717]
NPO13661 Tripterygium wilfordii Species Celastraceae Eukaryota n.a. leaf n.a. PMID[1823717]
NPO13661 Tripterygium wilfordii Species Celastraceae Eukaryota n.a. n.a. n.a. PMID[18554602]
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. n.a. n.a. PMID[18611049]
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. n.a. n.a. PMID[18768384]
NPO13661 Tripterygium wilfordii Species Celastraceae Eukaryota n.a. bark n.a. PMID[18996177]
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. n.a. n.a. PMID[19476340]
NPO13661 Tripterygium wilfordii Species Celastraceae Eukaryota n.a. root n.a. PMID[21486005]
NPO13661 Tripterygium wilfordii Species Celastraceae Eukaryota root n.a. n.a. PMID[21486005]
NPO13661 Tripterygium wilfordii Species Celastraceae Eukaryota n.a. n.a. n.a. PMID[21514608]
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. n.a. n.a. PMID[21912858]
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. cone n.a. PMID[22111577]
NPO13661 Tripterygium wilfordii Species Celastraceae Eukaryota dried roots purchased from Sichuan Neautus Traditional Chinese Medicine Co. Ltd. (Chengdu, P.R. China) n.a. PMID[22148431]
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. flower n.a. PMID[22166201]
NPO13661 Tripterygium wilfordii Species Celastraceae Eukaryota leaves n.a. n.a. PMID[23268606]
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. n.a. n.a. PMID[23790907]
NPO13661 Tripterygium wilfordii Species Celastraceae Eukaryota n.a. n.a. n.a. PMID[23852638]
NPO19231 Sophora flavescens Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[24295087]
NPO13661 Tripterygium wilfordii Species Celastraceae Eukaryota n.a. n.a. n.a. PMID[24549173]
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. n.a. n.a. PMID[24948953]
NPO13661 Tripterygium wilfordii Species Celastraceae Eukaryota n.a. n.a. n.a. PMID[24963543]
NPO13661 Tripterygium wilfordii Species Celastraceae Eukaryota n.a. n.a. n.a. PMID[25237706]
NPO13661 Tripterygium wilfordii Species Celastraceae Eukaryota n.a. bark n.a. PMID[2534610]
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. n.a. n.a. PMID[25564559]
NPO19231 Sophora flavescens Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[27575476]
NPO13661 Tripterygium wilfordii Species Celastraceae Eukaryota n.a. root n.a. PMID[2816380]
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. n.a. n.a. PMID[29154541]
NPO13661 Tripterygium wilfordii Species Celastraceae Eukaryota Leaves n.a. n.a. PMID[29355322]
NPO19231 Sophora flavescens Species Fabaceae Eukaryota Roots n.a. n.a. PMID[30298740]
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. n.a. n.a. PMID[30384263]
NPO13661 Tripterygium wilfordii Species Celastraceae Eukaryota Leaves n.a. n.a. PMID[31556299]
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. n.a. n.a. PMID[37631012]
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. n.a. n.a. PMID[38354824]
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. n.a. n.a. PMID[39199155]
NPO13661 Tripterygium wilfordii Species Celastraceae Eukaryota n.a. n.a. n.a. PMID[7102323]
NPO13661 Tripterygium wilfordii Species Celastraceae Eukaryota n.a. n.a. n.a. PMID[7304185]
NPO13661 Tripterygium wilfordii Species Celastraceae Eukaryota n.a. n.a. n.a. PMID[8699928]
NPO13661 Tripterygium wilfordii Species Celastraceae Eukaryota n.a. n.a. n.a. PMID[8722541]
NPO19231 Sophora flavescens Species Fabaceae Eukaryota Roots n.a. n.a. PMID[9868163]
NPO13661 Tripterygium wilfordii Species Celastraceae Eukaryota n.a. root n.a. Database[Article]
NPO19231 Sophora flavescens Species Fabaceae Eukaryota n.a. root n.a. Database[Article]
NPO13661 Tripterygium wilfordii Species Celastraceae Eukaryota n.a. n.a. n.a. Database[Article]
NPO13661 Tripterygium wilfordii Species Celastraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19231 Sophora flavescens Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO13661 Tripterygium wilfordii Species Celastraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO19231 Sophora flavescens Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO19231 Sophora flavescens Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO13661 Tripterygium wilfordii Species Celastraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO19231 Sophora flavescens Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO19231 Sophora flavescens Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO13879 Humulus lupulus Species Cannabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19231 Sophora flavescens Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13661 Tripterygium wilfordii Species Celastraceae 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 NPC104060 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
0.8276 Intermediate Similarity NPC76338
0.8276 Intermediate Similarity NPC250242
0.625 Remote Similarity NPC149026
0.625 Remote Similarity NPC148757
0.6143 Remote Similarity NPC485619
0.5909 Remote Similarity NPC220998
0.5882 Remote Similarity NPC161506
0.5833 Remote Similarity NPC177354
0.5735 Remote Similarity NPC291878
0.5692 Remote Similarity NPC164980
0.5692 Remote Similarity NPC76372
0.5692 Remote Similarity NPC37496
0.5672 Remote Similarity NPC310130
0.5625 Remote Similarity NPC259685
0.5606 Remote Similarity NPC107572
0.5606 Remote Similarity NPC32739
0.5556 Remote Similarity NPC473014
0.5522 Remote Similarity NPC250214
0.5479 Remote Similarity NPC485618
0.5441 Remote Similarity NPC480990
0.5405 Remote Similarity NPC77794
0.5405 Remote Similarity NPC225660
0.5373 Remote Similarity NPC236766
0.5373 Remote Similarity NPC150408
0.5373 Remote Similarity NPC39329
0.5373 Remote Similarity NPC476342
0.5373 Remote Similarity NPC51032
0.5362 Remote Similarity NPC316816
0.5333 Remote Similarity NPC235217
0.5333 Remote Similarity NPC485611
0.5294 Remote Similarity NPC69674
0.5217 Remote Similarity NPC66515
0.5211 Remote Similarity NPC155063
0.5147 Remote Similarity NPC1089
0.5072 Remote Similarity NPC265040
0.5072 Remote Similarity NPC75049
0.5072 Remote Similarity NPC156190

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC104060 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