Natural Product: NPC275472

Natural Product IDNPC275472
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (6E,10S)-6,10-Dimethyl-3-Propan-2-Ylidenecyclodec-6-Ene-1,4-Dione
IUPAC Name (6E,10S)-6,10-dimethyl-3-propan-2-ylidenecyclodec-6-ene-1,4-dione
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL113997
PubChem CID 10421549
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0000259] Prenol lipids
        • [CHEMONTID:0001550] Sesquiterpenoids
          • [CHEMONTID:0002456] Germacrane sesquiterpenoids

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 ZYPUZCWWTYIGFV-BCMYLCSRSA-N
Standard InCHI InChI=1S/C15H22O2/c1-10(2)13-9-14(16)12(4)7-5-6-11(3)8-15(13)17/h6,12H,5,7-9H2,1-4H3/b11-6+/t12-/m0/s1
SMILES C/C/1=CCC[C@H](C)C(=O)CC(=C(C)C)C(=O)C1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   234.16 Volume:   266.474
?
Van der Waals volume.
Dense:   0.879 LogP:   2.439
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.285
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.976
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   0.0 Rigid Bonds:   13.0
TPSA:   34.14
?
Topological Polar Surface Area.
 H-Bond Acceptor:   2.0
H-Bond Donor:   0.0 Rings:   1.0
Heavy Atoms:   2.0

MedChem Properties

QED Drug-Likeness Score:   0.474 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.231 Fsp3:   0.6
MCE-18:   21.75
?
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:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.057 Fluc inhibitor:   0.012
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.05
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.05
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.995 Promiscuous compounds:   0.427

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.499 MDCK Permeability:   -4.775
Pgp-inhibitor:   0.978 Pgp-substrate:   0.007
PAMPA:   0.05
?
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%):   0.006 30% Bioavailability (F30%):   0.024
50% Bioavailability (F50%):   0.768

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.003 MRP1:   0.967
Plasma Protein Binding (PPB):   86.334% Volume Distribution (VD):   0.119
Fu: 11.218%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.997
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.077
BSEP inhibitor:   0.999

ADMET: Metabolism

CYP1A2-inhibitor:   0.137 CYP1A2-substrate:   0.781
CYP2C19-inhibitor:   0.349 CYP2C19-substrate:   0.009
CYP2C9-inhibitor:   0.009 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.001 CYP2D6-substrate:   0.015
CYP3A4-inhibitor:   0.013 CYP3A4-substrate:   0.226
CYP2B6-substrate:   0.01 CYP2C8-inhibitor:   0.946
HLM stability:   0.911
?
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):  9.712 Half-life (T1/2):  0.918

ADMET: Toxicity

hERG Blockers:  0.045 hERG Blockers (10um):  0.189
Human Hepatotoxicity (H-HT):  0.627 Drug-induced Liver Injury (DILI):  0.199
AMES Toxicity:  0.444 Rat Oral Acute Toxicity:  0.26
Maximum Recommended Daily Dose:  0.427 Skin Sensitization:  0.847
Carcinogencity:  0.815 Eye Corrosion:  0.082
Eye Irritation:  0.845 Respiratory Toxicity:  0.541
Drug-induced Neurotoxicity:  0.377 Ototoxicity:  0.35
Hematotoxicity:  0.687 Drug-induced Nephrotoxicity:  0.581
Genotoxicity:  0.152 RPMI-8226 Immunitoxicity:  0.103
A549 Cytotoxicity:  0.133 Hek293 Cytotoxicity:  0.315
BCF:   0.825
?
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:   3.288
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.652
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.232
?
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
NPO24124 Curcuma longa Species Zingiberaceae Eukaryota n.a. n.a. n.a. PMID[12350137]
NPO24124 Curcuma longa Species Zingiberaceae Eukaryota rhizome n.a. n.a. PMID[12617587]
NPO28256 Platycladus orientalis Species Cupressaceae Eukaryota leaves Soorkesh Valley, Gollestan, Iran n.a. PMID[15104493]
NPO28256 Platycladus orientalis Species Cupressaceae Eukaryota Leaves and branches Soorkesh Valley, Gollestan, Iran n.a. PMID[15104493]
NPO24124 Curcuma longa Species Zingiberaceae Eukaryota Rhizomes n.a. n.a. PMID[23153397]
NPO24124 Curcuma longa Species Zingiberaceae Eukaryota n.a. leaf n.a. PMID[23901173]
NPO24124 Curcuma longa Species Zingiberaceae Eukaryota n.a. n.a. n.a. PMID[28068085]
NPO24124 Curcuma longa Species Zingiberaceae Eukaryota n.a. n.a. n.a. PMID[9584408]
NPO7929 Curcuma zedoaria Species Zingiberaceae Eukaryota n.a. n.a. n.a. PMID[9868158]
NPO33283 zedoariae rhizoma n.a. n.a. n.a. n.a. n.a. n.a. PMID[9871681]
NPO31384 Thuja orientalis Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24124 Curcuma longa Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28256 Platycladus orientalis Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3532 Tridentata marginata n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO9241 Adiantum capillus-veneris Species Pteridaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3251 Jacobaea maritima Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25160 Goniothalamus borneensis Species Annonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7308 Fraxinus quadrangulata Species Oleaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7929 Curcuma zedoaria Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24124 Curcuma longa Species Zingiberaceae Eukaryota n.a. n.a. Database[FooDB]
NPO24124 Curcuma longa Species Zingiberaceae Eukaryota Essential Oil n.a. n.a. Database[FooDB]
NPO24124 Curcuma longa Species Zingiberaceae Eukaryota Leaf n.a. n.a. Database[FooDB]
NPO24124 Curcuma longa Species Zingiberaceae Eukaryota Rhizome n.a. n.a. Database[FooDB]
NPO24124 Curcuma longa Species Zingiberaceae Eukaryota Rhizome Essent. Oil n.a. n.a. Database[FooDB]
NPO24124 Curcuma longa Species Zingiberaceae Eukaryota Root n.a. n.a. Database[FooDB]
NPO24124 Curcuma longa Species Zingiberaceae Eukaryota n.a. n.a. Database[FooDB]
NPO7308 Fraxinus quadrangulata Species Oleaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO9241 Adiantum capillus-veneris Species Pteridaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO7929 Curcuma zedoaria Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO24124 Curcuma longa Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO31384 Thuja orientalis Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO24124 Curcuma longa Species Zingiberaceae Eukaryota n.a. n.a. Database[Phenol-Explorer]
NPO9241 Adiantum capillus-veneris Species Pteridaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO7929 Curcuma zedoaria Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO24124 Curcuma longa Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO28256 Platycladus orientalis Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO3251 Jacobaea maritima Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO7308 Fraxinus quadrangulata Species Oleaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO28256 Platycladus orientalis Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO24124 Curcuma longa Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO31384 Thuja orientalis Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO9241 Adiantum capillus-veneris Species Pteridaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO7929 Curcuma zedoaria Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO24124 Curcuma longa Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO28256 Platycladus orientalis Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO7929 Curcuma zedoaria Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO9241 Adiantum capillus-veneris Species Pteridaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7929 Curcuma zedoaria Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3532 Tridentata marginata n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO7308 Fraxinus quadrangulata Species Oleaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25160 Goniothalamus borneensis Species Annonaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28256 Platycladus orientalis Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3251 Jacobaea maritima Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24124 Curcuma longa Species Zingiberaceae 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
NPT112 Cell line MOLT-4 Homo sapiens IC50 > 100.0 ug.mL-1 PMID[29274817]
NPT112 Cell line MOLT-4 Homo sapiens IC50 = 35.0 ug.mL-1 PMID[29274817]
NPT112 Cell line MOLT-4 Homo sapiens Activity = 55.25 % PMID[29274817]
NPT83 Cell line MCF7 Homo sapiens IC50 = 33000000.0 ug.mL-1 PMID[29274817]
NPT2306 Cell line Ca-Ski Homo sapiens IC50 = 21700000.0 ug.mL-1 PMID[29274817]
NPT306 Cell line PC-3 Homo sapiens IC50 = 19100000.0 ug.mL-1 PMID[29274817]
NPT139 Cell line HT-29 Homo sapiens IC50 = 22700000.0 ug.mL-1 PMID[29274817]
NPT737 Cell line HUVEC Homo sapiens IC50 = 24000000.0 ug.mL-1 PMID[29274817]
NPT112 Cell line MOLT-4 Homo sapiens Activity = 49.44 % PMID[29274817]
NPT23712 Cell line KG-1a Homo sapiens IC50 > 100.0 ug.mL-1 PMID[29274817]
NPT23712 Cell line KG-1a Homo sapiens IC20 = 30.0 ug ml-1 PMID[29274817]
NPT23712 Cell line KG-1a Homo sapiens Activity = 44.3 % PMID[29274817]
NPT23712 Cell line KG-1a Homo sapiens Activity = 19.92 % PMID[29274817]

In vivo activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT32 Organism Mus musculus Mus musculus Inhibition = 49.7 % PMID[9871681]
NPT32 Organism Mus musculus Mus musculus Inhibition = 46.2 % PMID[9871681]
NPT32 Organism Mus musculus Mus musculus Inhibition = 53.7 % PMID[9871681]
NPT29 Organism Rattus norvegicus Rattus norvegicus Inhibition = -6.3 % PMID[9871681]





 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 NPC275472 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
0.5676 Remote Similarity NPC63396
0.5676 Remote Similarity NPC202850
0.5135 Remote Similarity NPC301972

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC275472 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