Natural Product: NPC125705

Natural Product IDNPC125705
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 UPNVKIZABMRHNR-ZUYWJZQFSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 6436774
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0000259] Prenol lipids
        • [CHEMONTID:0001283] Terpene lactones
          • [CHEMONTID:0001543] Sesquiterpene lactones
            • [CHEMONTID:0001771] Germacranolides and derivatives

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 UPNVKIZABMRHNR-ZUYWJZQFSA-N
Standard InCHI InChI=1S/C17H22O4/c1-10-6-5-7-11(2)9-15-16(12(3)17(19)21-15)14(8-10)20-13(4)18/h6,9,14-16H,3,5,7-8H2,1-2,4H3/b10-6-,11-9-
SMILES C/C/1=C/CC/C(=CC2C(C(=C)C(=O)O2)C(C1)OC(=O)C)/C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   290.15 Volume:   307.454
?
Van der Waals volume.
Dense:   0.944 LogP:   2.31
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.441
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.669
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   17.0
TPSA:   52.6
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   0.0 Rings:   2.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.423 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.421 Fsp3:   0.529
MCE-18:   34.462
?
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:   0.213 Fluc inhibitor:   0.002
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.024
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.385
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.636 Promiscuous compounds:   0.01

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.583 MDCK Permeability:   -4.607
Pgp-inhibitor:   0.878 Pgp-substrate:   0.393
PAMPA:   0.403
?
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):   0.869
20% Bioavailability (F20%):   0.588 30% Bioavailability (F30%):   0.987
50% Bioavailability (F50%):   0.991

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.041 MRP1:   0.939
Plasma Protein Binding (PPB):   91.768% Volume Distribution (VD):   -0.176
Fu: 8.986%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.959
OATP1B3 inhibitor:   0.983 BCRP inhibitor:   0.039
BSEP inhibitor:   0.944

ADMET: Metabolism

CYP1A2-inhibitor:   0.015 CYP1A2-substrate:   0.097
CYP2C19-inhibitor:   0.648 CYP2C19-substrate:   0.013
CYP2C9-inhibitor:   0.052 CYP2C9-substrate:   0.11
CYP2D6-inhibitor:   0.003 CYP2D6-substrate:   0.551
CYP3A4-inhibitor:   0.221 CYP3A4-substrate:   0.033
CYP2B6-substrate:   0.026 CYP2C8-inhibitor:   0.973
HLM stability:   0.931
?
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):  6.59 Half-life (T1/2):  0.986

ADMET: Toxicity

hERG Blockers:  0.005 hERG Blockers (10um):  0.181
Human Hepatotoxicity (H-HT):  0.932 Drug-induced Liver Injury (DILI):  0.975
AMES Toxicity:  0.318 Rat Oral Acute Toxicity:  0.168
Maximum Recommended Daily Dose:  0.947 Skin Sensitization:  1.0
Carcinogencity:  0.731 Eye Corrosion:  0.197
Eye Irritation:  0.714 Respiratory Toxicity:  0.019
Drug-induced Neurotoxicity:  0.453 Ototoxicity:  0.549
Hematotoxicity:  0.335 Drug-induced Nephrotoxicity:  0.656
Genotoxicity:  0.254 RPMI-8226 Immunitoxicity:  0.089
A549 Cytotoxicity:  0.095 Hek293 Cytotoxicity:  0.6
BCF:   1.225
?
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:   3.848
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.661
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.12
?
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
NPO29841 Taxus yunnanensis Species Taxaceae Eukaryota n.a. n.a. n.a. PMID[12217376]
NPO29841 Taxus yunnanensis Species Taxaceae Eukaryota wood n.a. n.a. PMID[12444707]
NPO29841 Taxus yunnanensis Species Taxaceae Eukaryota wood Yunnang Province, China 2000-OCT PMID[21138310]
NPO29841 Taxus yunnanensis Species Taxaceae Eukaryota n.a. xylem n.a. PMID[21138310]
NPO12721 Liriodendron tulipifera Species Magnoliaceae Eukaryota n.a. n.a. n.a. PMID[23501116]
NPO12721 Liriodendron tulipifera Species Magnoliaceae Eukaryota n.a. n.a. n.a. PMID[31444719]
NPO15125.2 Taxus wallichiana var. wallichiana Varieties Taxaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12721 Liriodendron tulipifera Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14295 Ambrosia chamissonis Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4652 Ambrosia dumosa Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12721 Liriodendron tulipifera Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO14295 Ambrosia chamissonis Species Asteraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO4652 Ambrosia dumosa Species Asteraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO29841 Taxus yunnanensis Species Taxaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO12721 Liriodendron tulipifera Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO14295 Ambrosia chamissonis Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO4652 Ambrosia dumosa Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO15125.2 Taxus wallichiana var. wallichiana Varieties Taxaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO12721 Liriodendron tulipifera Species Magnoliaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO29841 Taxus yunnanensis Species Taxaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO14295 Ambrosia chamissonis Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4652 Ambrosia dumosa Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15125.2 Taxus wallichiana var. wallichiana Varieties Taxaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12721 Liriodendron tulipifera Species Magnoliaceae 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 NPC125705 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
1.0 High Similarity NPC171204
1.0 High Similarity NPC606745
0.878 High Similarity NPC611318
0.7347 Intermediate Similarity NPC470755
0.7347 Intermediate Similarity NPC298801
0.7045 Intermediate Similarity NPC97516
0.66 Remote Similarity NPC481909
0.66 Remote Similarity NPC158756
0.66 Remote Similarity NPC601035
0.6226 Remote Similarity NPC469910
0.6222 Remote Similarity NPC58956
0.6222 Remote Similarity NPC163003
0.6222 Remote Similarity NPC295633
0.6222 Remote Similarity NPC269206
0.6182 Remote Similarity NPC481911
0.6122 Remote Similarity NPC476028
0.6122 Remote Similarity NPC270126
0.6038 Remote Similarity NPC605339
0.5849 Remote Similarity NPC281132
0.5636 Remote Similarity NPC131669
0.5625 Remote Similarity NPC167881
0.5625 Remote Similarity NPC98557
0.5577 Remote Similarity NPC151770
0.5577 Remote Similarity NPC250940
0.5577 Remote Similarity NPC165383
0.5577 Remote Similarity NPC169575
0.5556 Remote Similarity NPC266957
0.5556 Remote Similarity NPC482131
0.549 Remote Similarity NPC609300
0.549 Remote Similarity NPC610417
0.5472 Remote Similarity NPC473390
0.5472 Remote Similarity NPC194871
0.5472 Remote Similarity NPC488296
0.5455 Remote Similarity NPC482130
0.5455 Remote Similarity NPC482128
0.5455 Remote Similarity NPC482129
0.5385 Remote Similarity NPC470256
0.5385 Remote Similarity NPC50637
0.5385 Remote Similarity NPC476355
0.537 Remote Similarity NPC178702
0.5357 Remote Similarity NPC481806
0.5357 Remote Similarity NPC269509
0.5357 Remote Similarity NPC17585
0.5283 Remote Similarity NPC116177
0.5283 Remote Similarity NPC7563
0.5273 Remote Similarity NPC482126
0.5273 Remote Similarity NPC320630
0.5273 Remote Similarity NPC250315
0.5263 Remote Similarity NPC40746
0.52 Remote Similarity NPC140287
0.5179 Remote Similarity NPC307411
0.5172 Remote Similarity NPC134725
0.5172 Remote Similarity NPC48657
0.5172 Remote Similarity NPC483718
0.5098 Remote Similarity NPC301477
0.5098 Remote Similarity NPC25684
0.5098 Remote Similarity NPC488306
0.5094 Remote Similarity NPC600792
0.5094 Remote Similarity NPC610427
0.5091 Remote Similarity NPC473619
0.5091 Remote Similarity NPC272814
0.5088 Remote Similarity NPC482127

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC125705 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