Natural Product: NPC84312

Natural Product IDNPC84312
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 NZMHIKFTAXRIDL-HFTJROMGSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0000259] Prenol lipids
        • [CHEMONTID:0001551] Diterpenoids
          • [CHEMONTID:0001757] Colensane and clerodane diterpenoids

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 NZMHIKFTAXRIDL-HFTJROMGSA-N
Standard InCHI InChI=1S/C20H32O4/c1-14-11-16(22)17-18(2,13-21)7-4-8-19(17,3)20(14,23)9-5-15-6-10-24-12-15/h6,10,12,14,16-17,21-23H,4-5,7-9,11,13H2,1-3H3/t14-,16-,17-,18-,19+,20-/m1/s1
SMILES C[C@@H]1C[C@H]([C@@H]2[C@](C)(CCC[C@]2(C)[C@]1(CCc1ccoc1)O)CO)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   336.23 Volume:   358.695
?
Van der Waals volume.
Dense:   0.937 LogP:   2.014
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.288
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.485
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   16.0
TPSA:   73.83
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   3.0 Rings:   3.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.79 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.678 Fsp3:   0.8
MCE-18:   78.222
?
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:   0.191 Fluc inhibitor:   0.0
?
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:   0.004
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.113 Promiscuous compounds:   0.255

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.978 MDCK Permeability:   -4.766
Pgp-inhibitor:   0.237 Pgp-substrate:   0.687
PAMPA:   0.901
?
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):   0.132
20% Bioavailability (F20%):   0.852 30% Bioavailability (F30%):   0.558
50% Bioavailability (F50%):   0.948

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.691 MRP1:   0.632
Plasma Protein Binding (PPB):   74.721% Volume Distribution (VD):   -0.325
Fu: 24.973%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.847
OATP1B3 inhibitor:   0.397 BCRP inhibitor:   0.649
BSEP inhibitor:   0.807

ADMET: Metabolism

CYP1A2-inhibitor:   0.002 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.02 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.082 CYP2C9-substrate:   0.002
CYP2D6-inhibitor:   0.523 CYP2D6-substrate:   0.171
CYP3A4-inhibitor:   0.099 CYP3A4-substrate:   0.559
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.377
HLM stability:   0.0
?
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):  12.958 Half-life (T1/2):  1.675

ADMET: Toxicity

hERG Blockers:  0.212 hERG Blockers (10um):  0.415
Human Hepatotoxicity (H-HT):  0.542 Drug-induced Liver Injury (DILI):  0.175
AMES Toxicity:  0.214 Rat Oral Acute Toxicity:  0.248
Maximum Recommended Daily Dose:  0.85 Skin Sensitization:  0.439
Carcinogencity:  0.685 Eye Corrosion:  0.002
Eye Irritation:  0.542 Respiratory Toxicity:  0.409
Drug-induced Neurotoxicity:  0.075 Ototoxicity:  0.736
Hematotoxicity:  0.189 Drug-induced Nephrotoxicity:  0.613
Genotoxicity:  0.179 RPMI-8226 Immunitoxicity:  0.057
A549 Cytotoxicity:  0.097 Hek293 Cytotoxicity:  0.325
BCF:   0.489
?
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:   3.053
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.253
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.539
?
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
NPO24498 Casearia membranacea Species Salicaceae Eukaryota n.a. leaf n.a. PMID[14709876]
NPO24498 Casearia membranacea Species Salicaceae Eukaryota n.a. twig n.a. PMID[14709876]
NPO24498 Casearia membranacea Species Salicaceae Eukaryota Leaves; Twigs n.a. n.a. PMID[15043402]
NPO23473 Cinnamomum kotoense Species Lauraceae Eukaryota stem wood n.a. n.a. PMID[16180806]
NPO24498 Casearia membranacea Species Salicaceae Eukaryota n.a. n.a. n.a. PMID[16309320]
NPO23473 Cinnamomum kotoense Species Lauraceae Eukaryota leaves n.a. n.a. PMID[16792412]
NPO23769 Ainsliaea macrocephala Species Asteraceae Eukaryota n.a. whole plant n.a. PMID[18484734]
NPO23473 Cinnamomum kotoense Species Lauraceae Eukaryota n.a. n.a. n.a. PMID[18489163]
NPO23557 Zanthoxylum ailanthoides Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[19128011]
NPO24301 Buxus microphylla Species Buxaceae Eukaryota leaves and stems Kunming, Yunnan, China 2007-AUG PMID[19133780]
NPO18735 Pinus mugo Species Pinaceae Eukaryota n.a. n.a. n.a. PMID[31475763]
NPO23264 Marrubium vulgare Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[31983544]
NPO25037 Nepeta cataria Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[32092043]
NPO25037 Nepeta cataria Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[36866384]
NPO23264 Marrubium vulgare Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[36929733]
NPO25037 Nepeta cataria Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[37151483]
NPO23264 Marrubium vulgare Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[38931446]
NPO21352 Boronia ternata Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23721 Epidendrum rigidum Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24993 Conospermum teretifolium Species Proteaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23849 Dicoma anomala Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24462 Pityrogramma ebenea Species Pteridaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24952 Galeopsis tetrahit Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23896 Cytisus ratisbonensis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23264 Marrubium vulgare Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23557 Zanthoxylum ailanthoides Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25037 Nepeta cataria Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18735 Pinus mugo Species Pinaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24498 Casearia membranacea Species Salicaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO25037 Nepeta cataria Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO24498 Casearia membranacea Species Salicaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO24301 Buxus microphylla Species Buxaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO23302 Strychnos camptoneura Species Loganiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO23557 Zanthoxylum ailanthoides Species Rutaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO23264 Marrubium vulgare Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO23557 Zanthoxylum ailanthoides Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO23302 Strychnos camptoneura Species Loganiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO23264 Marrubium vulgare Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO24301 Buxus microphylla Species Buxaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO25037 Nepeta cataria Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO21478 Buxus hyrcana Species Buxaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO24498 Casearia membranacea Species Salicaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO23264 Marrubium vulgare Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO24301 Buxus microphylla Species Buxaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO25037 Nepeta cataria Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO25037 Nepeta cataria Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21352 Boronia ternata Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23302 Strychnos camptoneura Species Loganiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24015 Perknaster fuscus Species Ganeriidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24258 Vellozia nivea Species Velloziaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23769 Ainsliaea macrocephala Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23849 Dicoma anomala Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24301 Buxus microphylla Species Buxaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21478 Buxus hyrcana Species Buxaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23896 Cytisus ratisbonensis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25080 Sphaeria maculans n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO18735 Pinus mugo Species Pinaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24952 Galeopsis tetrahit Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23930 Luculia pinceana Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24462 Pityrogramma ebenea Species Pteridaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28748 Aphis sambuci Species Aphididae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23473 Cinnamomum kotoense Species Lauraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24993 Conospermum teretifolium Species Proteaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23428 Tinus mamillata n.a. n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO20498 Cephalaria ambrosioides Species Caprifoliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23474 Abies veitchii Species Pinaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22684 Enrichment culture Species n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO23264 Marrubium vulgare Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18918 Lecanicillium muscarium Species Cordycipitaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24498 Casearia membranacea Species Salicaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23721 Epidendrum rigidum Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23557 Zanthoxylum ailanthoides Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7197 Colchicum robustum Species Colchicaceae 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 NPC84312 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 NPC67003
0.6481 Remote Similarity NPC5676
0.55 Remote Similarity NPC243577
0.5469 Remote Similarity NPC125182
0.5357 Remote Similarity NPC485403
0.5333 Remote Similarity NPC46896
0.5312 Remote Similarity NPC121158
0.5231 Remote Similarity NPC251865
0.5079 Remote Similarity NPC260562

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC84312 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