Natural Product: NPC93181

Natural Product IDNPC93181
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 KIXMQGXACFNMEM-FQEVSTJZSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL3814422
PubChem CID 403772
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0002448] Benzenoids
      • [CHEMONTID:0000023] Naphthalenes

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 KIXMQGXACFNMEM-FQEVSTJZSA-N
Standard InCHI InChI=1S/C20H26O2/c1-12(2)16-11-14-9-8-13(3)15-7-6-10-19(4,5)20(22,17(14)15)18(16)21/h8-9,11-12,22H,6-7,10H2,1-5H3/t20-/m0/s1
SMILES CC(C1=Cc2ccc(c3c2[C@@](C1=O)(O)C(C)(C)CCC3)C)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   298.19 Volume:   333.205
?
Van der Waals volume.
Dense:   0.895 LogP:   3.954
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.617
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.567
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   17.0
TPSA:   37.3
?
Topological Polar Surface Area.
 H-Bond Acceptor:   2.0
H-Bond Donor:   1.0 Rings:   3.0
Heavy Atoms:   2.0

MedChem Properties

QED Drug-Likeness Score:   0.845 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.561 Fsp3:   0.55
MCE-18:   73.097
?
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:   0.134 Fluc inhibitor:   0.217
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.257
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.419
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.259 Promiscuous compounds:   0.183

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.683 MDCK Permeability:   -4.712
Pgp-inhibitor:   0.965 Pgp-substrate:   0.101
PAMPA:   0.094
?
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%):   0.086 30% Bioavailability (F30%):   0.061
50% Bioavailability (F50%):   0.989

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.488 MRP1:   0.999
Plasma Protein Binding (PPB):   94.76% Volume Distribution (VD):   0.494
Fu: 3.559%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.997
OATP1B3 inhibitor:   0.869 BCRP inhibitor:   0.144
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.943 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.977
CYP2C9-inhibitor:   0.907 CYP2C9-substrate:   0.286
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.998
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.895 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):  10.236 Half-life (T1/2):  0.676

ADMET: Toxicity

hERG Blockers:  0.048 hERG Blockers (10um):  0.27
Human Hepatotoxicity (H-HT):  0.752 Drug-induced Liver Injury (DILI):  0.189
AMES Toxicity:  0.718 Rat Oral Acute Toxicity:  0.546
Maximum Recommended Daily Dose:  0.739 Skin Sensitization:  0.823
Carcinogencity:  0.734 Eye Corrosion:  0.01
Eye Irritation:  0.762 Respiratory Toxicity:  0.772
Drug-induced Neurotoxicity:  0.142 Ototoxicity:  0.516
Hematotoxicity:  0.591 Drug-induced Nephrotoxicity:  0.706
Genotoxicity:  0.837 RPMI-8226 Immunitoxicity:  0.09
A549 Cytotoxicity:  0.079 Hek293 Cytotoxicity:  0.499
BCF:   2.817
?
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:   4.476
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.619
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.517
?
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
NPO16570 Didemnum obscurum Species Didemnidae Eukaryota n.a. Tiruchandur coast in the Gulf of Mannar, Tamilnadu, India 2002-FEB PMID[15270574]
NPO19278 Taxodium distichum Species Cupressaceae Eukaryota n.a. n.a. n.a. PMID[17869103]
NPO13852 Pachysandra terminalis Species Buxaceae Eukaryota n.a. n.a. n.a. PMID[22804108]
NPO19278 Taxodium distichum Species Cupressaceae Eukaryota n.a. n.a. n.a. PMID[26905523]
NPO16570 Didemnum obscurum Species Didemnidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19278 Taxodium distichum Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10233 Nicotiana trigonophylla Species Solanaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12898 Rhaphiolepis umbellata Species Rosaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13852 Pachysandra terminalis Species Buxaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14820 Petasites spurius Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO22284 Acacia myrtifolia Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21045 Salvia staminea Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19313 Herniaria fontanesii Species Caryophyllaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5795 Koelpinia linearis Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21044 Sphaerellopsis filum Species Leptosphaeriaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2052 Hedyotis acutangula Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO19278 Taxodium distichum Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO21045 Salvia staminea Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO13852 Pachysandra terminalis Species Buxaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO5795 Koelpinia linearis Species Asteraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO21045 Salvia staminea Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO2052 Hedyotis acutangula Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO19278 Taxodium distichum Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO15519 Lysimachia candida Species Primulaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO13852 Pachysandra terminalis Species Buxaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO5795 Koelpinia linearis Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO13852 Pachysandra terminalis Species Buxaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO19247 Viburnum jucundum Species Adoxaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21044 Sphaerellopsis filum Species Leptosphaeriaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14820 Petasites spurius Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19835 Melodorum oldhamii Species Annonaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2052 Hedyotis acutangula Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27607 Saussurea candicans Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22377 Lechevalieria flava Species Pseudonocardiaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO5795 Koelpinia linearis Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12898 Rhaphiolepis umbellata Species Rosaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11191 Campylospermum flavum Species Ochnaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18607 Eria macrophylla Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13852 Pachysandra terminalis Species Buxaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10233 Nicotiana trigonophylla Species Solanaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19278 Taxodium distichum Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22284 Acacia myrtifolia Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15519 Lysimachia candida Species Primulaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16334 Polystictus versicolor Species Tyrannidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19313 Herniaria fontanesii Species Caryophyllaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21045 Salvia staminea Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18270 Betula divaricata Species Betulaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16570 Didemnum obscurum Species Didemnidae 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
NPT633 Organism Leishmania donovani Leishmania donovani IC50 > 10.0 ug.mL-1 PMID[26905523]
NPT634 Organism Leishmania amazonensis Leishmania amazonensis IC50 > 10.0 ug.mL-1 PMID[26905523]

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 NPC93181 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
0.7143 Intermediate Similarity NPC600071
0.5254 Remote Similarity NPC486045

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC93181 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