Natural Product: NPC42431

Natural Product IDNPC42431
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 CVIVANCKIBYAOP-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 72982958
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 CVIVANCKIBYAOP-UHFFFAOYSA-N
Standard InCHI InChI=1S/C15H18O3/c1-9-5-4-6-15(3)14(18-15)13(16)12-10(2)8-17-11(12)7-9/h5,8,14H,4,6-7H2,1-3H3
SMILES CC1=CCCC2(C)C(C(=O)c3c(C)coc3C1)O2

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   246.13 Volume:   258.152
?
Van der Waals volume.
Dense:   0.953 LogP:   3.014
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.034
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.738
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   0.0 Rigid Bonds:   17.0
TPSA:   42.74
?
Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   0.0 Rings:   3.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.521 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.694 Fsp3:   0.533
MCE-18:   61.826
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Accepted GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.107 Fluc inhibitor:   0.001
?
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:   0.353
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.425 Promiscuous compounds:   0.005

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.426 MDCK Permeability:   -4.524
Pgp-inhibitor:   0.698 Pgp-substrate:   0.204
PAMPA:   0.462
?
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):   0.038
20% Bioavailability (F20%):   0.129 30% Bioavailability (F30%):   0.366
50% Bioavailability (F50%):   0.671

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.157 MRP1:   0.973
Plasma Protein Binding (PPB):   93.521% Volume Distribution (VD):   0.189
Fu: 5.16%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.858
OATP1B3 inhibitor:   0.791 BCRP inhibitor:   0.095
BSEP inhibitor:   0.964

ADMET: Metabolism

CYP1A2-inhibitor:   0.642 CYP1A2-substrate:   0.315
CYP2C19-inhibitor:   0.962 CYP2C19-substrate:   0.321
CYP2C9-inhibitor:   0.129 CYP2C9-substrate:   0.003
CYP2D6-inhibitor:   0.148 CYP2D6-substrate:   0.075
CYP3A4-inhibitor:   0.873 CYP3A4-substrate:   0.206
CYP2B6-substrate:   0.329 CYP2C8-inhibitor:   0.132
HLM stability:   0.923
?
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):  9.879 Half-life (T1/2):  1.169

ADMET: Toxicity

hERG Blockers:  0.042 hERG Blockers (10um):  0.311
Human Hepatotoxicity (H-HT):  0.503 Drug-induced Liver Injury (DILI):  0.6
AMES Toxicity:  0.546 Rat Oral Acute Toxicity:  0.625
Maximum Recommended Daily Dose:  0.568 Skin Sensitization:  0.763
Carcinogencity:  0.801 Eye Corrosion:  0.182
Eye Irritation:  0.89 Respiratory Toxicity:  0.421
Drug-induced Neurotoxicity:  0.403 Ototoxicity:  0.164
Hematotoxicity:  0.363 Drug-induced Nephrotoxicity:  0.098
Genotoxicity:  0.877 RPMI-8226 Immunitoxicity:  0.086
A549 Cytotoxicity:  0.149 Hek293 Cytotoxicity:  0.17
BCF:   2.278
?
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:   4.159
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.389
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.119
?
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
NPO22741 Curcuma kwangsiensis Species Zingiberaceae Eukaryota n.a. rhizome n.a. DOI[10.1021/np100392m]
NPO22741 Curcuma kwangsiensis Species Zingiberaceae Eukaryota Rhizomes n.a. n.a. PMID[20879743]
NPO22741 Curcuma kwangsiensis Species Zingiberaceae Eukaryota n.a. n.a. n.a. PMID[21807513]
NPO2618 Curcuma wenyujin Species Zingiberaceae Eukaryota n.a. rhizome n.a. PMID[23738470]
NPO2618 Curcuma wenyujin Species Zingiberaceae Eukaryota n.a. root n.a. PMID[23738470]
NPO18068 Curcuma phaeocaulis Species Zingiberaceae Eukaryota rhizomes n.a. n.a. PMID[23755850]
NPO2618 Curcuma wenyujin Species Zingiberaceae Eukaryota Rhizomes n.a. n.a. PMID[25275213]
NPO7929 Curcuma zedoaria Species Zingiberaceae Eukaryota n.a. n.a. n.a. PMID[9868158]
NPO7929 Curcuma zedoaria Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2618 Curcuma wenyujin Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18068 Curcuma phaeocaulis Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO22741 Curcuma kwangsiensis Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7929 Curcuma zedoaria Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO22741 Curcuma kwangsiensis Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO7929 Curcuma zedoaria Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO22741 Curcuma kwangsiensis Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO22741 Curcuma kwangsiensis Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO2618 Curcuma wenyujin Species Zingiberaceae 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]
NPO18068 Curcuma phaeocaulis Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO22741 Curcuma kwangsiensis Species Zingiberaceae 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]
NPO2618 Curcuma wenyujin Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO2618 Curcuma wenyujin Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7929 Curcuma zedoaria Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22741 Curcuma kwangsiensis Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18068 Curcuma phaeocaulis 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

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 NPC42431 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 NPC200718
0.6724 Remote Similarity NPC478463
0.5738 Remote Similarity NPC296539
0.5312 Remote Similarity NPC248795

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC42431 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