Natural Product: NPC99154

Natural Product IDNPC99154
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 BQLIBSZGTNAGNT-OQOGXPRXSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 10085628
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0000259] Prenol lipids
        • [CHEMONTID:0001550] 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 BQLIBSZGTNAGNT-OQOGXPRXSA-N
Standard InCHI InChI=1S/C18H26O3/c1-12-6-9-15-17(3,14(12)8-7-13(2)19)10-5-11-18(15,4)16(20)21/h7-8,14-15H,1,5-6,9-11H2,2-4H3,(H,20,21)/b8-7+/t14-,15+,17+,18-/m0/s1
SMILES C=C1CC[C@@H]2[C@](C)(CCC[C@]2(C)C(=O)O)[C@H]1/C=C/C(=O)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   290.19 Volume:   318.596
?
Van der Waals volume.
Dense:   0.911 LogP:   2.799
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.508
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.892
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   15.0
TPSA:   54.37
?
Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   1.0 Rings:   2.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.631 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.162 Fsp3:   0.667
MCE-18:   44.2
?
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:   0.11 Fluc inhibitor:   0.002
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.022
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.009
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.881 Promiscuous compounds:   0.484

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.797 MDCK Permeability:   -4.852
Pgp-inhibitor:   0.136 Pgp-substrate:   0.0
PAMPA:   0.454
?
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%):   0.007 30% Bioavailability (F30%):   0.004
50% Bioavailability (F50%):   0.083

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.007 MRP1:   0.935
Plasma Protein Binding (PPB):   88.565% Volume Distribution (VD):   -0.536
Fu: 6.992%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   0.995 BCRP inhibitor:   0.0
BSEP inhibitor:   0.994

ADMET: Metabolism

CYP1A2-inhibitor:   0.055 CYP1A2-substrate:   0.025
CYP2C19-inhibitor:   0.688 CYP2C19-substrate:   0.027
CYP2C9-inhibitor:   0.99 CYP2C9-substrate:   0.001
CYP2D6-inhibitor:   0.009 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.218 CYP3A4-substrate:   0.12
CYP2B6-substrate:   0.13 CYP2C8-inhibitor:   0.96
HLM stability:   0.052
?
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):  2.388 Half-life (T1/2):  1.012

ADMET: Toxicity

hERG Blockers:  0.04 hERG Blockers (10um):  0.126
Human Hepatotoxicity (H-HT):  0.778 Drug-induced Liver Injury (DILI):  0.615
AMES Toxicity:  0.226 Rat Oral Acute Toxicity:  0.294
Maximum Recommended Daily Dose:  0.561 Skin Sensitization:  0.962
Carcinogencity:  0.666 Eye Corrosion:  0.558
Eye Irritation:  0.978 Respiratory Toxicity:  0.812
Drug-induced Neurotoxicity:  0.439 Ototoxicity:  0.372
Hematotoxicity:  0.275 Drug-induced Nephrotoxicity:  0.504
Genotoxicity:  0.597 RPMI-8226 Immunitoxicity:  0.037
A549 Cytotoxicity:  0.029 Hek293 Cytotoxicity:  0.085
BCF:   0.942
?
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:   3.783
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.318
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.722
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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
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]
NPO6741 Metasequoia glyptostroboides Species Cupressaceae Eukaryota n.a. leaf n.a. PMID[21226514]
NPO6741 Metasequoia glyptostroboides Species Cupressaceae Eukaryota n.a. n.a. n.a. PMID[21226514]
NPO6741 Metasequoia glyptostroboides Species Cupressaceae Eukaryota n.a. stem n.a. PMID[21226514]
NPO28905 Biancaea decapetala Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[27966950]
NPO6741 Metasequoia glyptostroboides Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28256 Platycladus orientalis Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO6741 Metasequoia glyptostroboides Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO28256 Platycladus orientalis Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO6741 Metasequoia glyptostroboides Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO28905 Biancaea decapetala Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO28256 Platycladus orientalis Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO28256 Platycladus orientalis Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO6741 Metasequoia glyptostroboides Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28905 Biancaea decapetala Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28256 Platycladus orientalis Species Cupressaceae 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
NPT179 Cell line A2780 Homo sapiens IC50 > 10000.0 nM PMID[27966950]
NPT319 Cell line B16 Mus musculus IC50 > 10000.0 nM PMID[27966950]
NPT15392 Cell line Panc02 Mus musculus IC50 > 10000.0 nM PMID[27966950]
NPT2 Others Unspecified n.a. IC50 > 10000.0 nM PMID[27966950]

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 NPC99154 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
0.6415 Remote Similarity NPC471159
0.6415 Remote Similarity NPC123880
0.6226 Remote Similarity NPC59436
0.6154 Remote Similarity NPC481630
0.6071 Remote Similarity NPC40228
0.6038 Remote Similarity NPC198240
0.6038 Remote Similarity NPC237591
0.6038 Remote Similarity NPC72343
0.6038 Remote Similarity NPC3753
0.5965 Remote Similarity NPC232344
0.5965 Remote Similarity NPC600691
0.5849 Remote Similarity NPC488498
0.5849 Remote Similarity NPC61952
0.5849 Remote Similarity NPC603184
0.5818 Remote Similarity NPC18819
0.5818 Remote Similarity NPC46610
0.5763 Remote Similarity NPC14203
0.5763 Remote Similarity NPC229584
0.5763 Remote Similarity NPC477782
0.5741 Remote Similarity NPC36616
0.5714 Remote Similarity NPC269543
0.5714 Remote Similarity NPC247783
0.5714 Remote Similarity NPC239098
0.5667 Remote Similarity NPC477783
0.5636 Remote Similarity NPC165711
0.5536 Remote Similarity NPC91369
0.5455 Remote Similarity NPC161923
0.5455 Remote Similarity NPC183503
0.5455 Remote Similarity NPC283908
0.5455 Remote Similarity NPC103958
0.5455 Remote Similarity NPC610917
0.52 Remote Similarity NPC60772
0.5172 Remote Similarity NPC610334
0.5167 Remote Similarity NPC471037
0.5091 Remote Similarity NPC330659
0.5091 Remote Similarity NPC244708
0.5091 Remote Similarity NPC161187
0.5088 Remote Similarity NPC212661
0.5088 Remote Similarity NPC471035
0.5088 Remote Similarity NPC109854
0.5088 Remote Similarity NPC605179

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC99154 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