Natural Product: NPC125091

Natural Product IDNPC125091
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 ORNBQBCIOKFOEO-STZXPNGSSA-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:0000258] Steroids and steroid derivatives
        • [CHEMONTID:0003569] Pregnane steroids
          • [CHEMONTID:0001468] Gluco/mineralocorticoids, progestogins and derivatives

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 ORNBQBCIOKFOEO-STZXPNGSSA-N
Standard InCHI InChI=1S/C21H32O2/c1-13(22)17-6-7-18-16-5-4-14-12-15(23)8-10-20(14,2)19(16)9-11-21(17,18)3/h4,15-19,23H,5-12H2,1-3H3/t15-,16?,17-,18+,19+,20+,21-/m1/s1
SMILES CC(=O)[C@H]1CC[C@H]2C3CC=C4C[C@@H](CC[C@]4(C)[C@H]3CC[C@]12C)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   316.24 Volume:   349.854
?
Van der Waals volume.
Dense:   0.904 LogP:   4.403
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   4.105
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.815
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   21.0
TPSA:   37.3
?
Topological Polar Surface Area.
 H-Bond Acceptor:   2.0
H-Bond Donor:   1.0 Rings:   4.0
Heavy Atoms:   2.0

MedChem Properties

QED Drug-Likeness Score:   0.722 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.079 Fsp3:   0.857
MCE-18:   69.231
?
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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.716 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.011
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.0
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.589 Promiscuous compounds:   0.135

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.736 MDCK Permeability:   -4.8
Pgp-inhibitor:   0.029 Pgp-substrate:   0.179
PAMPA:   0.266
?
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%):   0.009 30% Bioavailability (F30%):   0.011
50% Bioavailability (F50%):   0.589

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.942 MRP1:   0.13
Plasma Protein Binding (PPB):   69.1% Volume Distribution (VD):   -0.005
Fu: 31.915%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.815
OATP1B3 inhibitor:   0.97 BCRP inhibitor:   0.518
BSEP inhibitor:   0.085

ADMET: Metabolism

CYP1A2-inhibitor:   0.032 CYP1A2-substrate:   0.023
CYP2C19-inhibitor:   0.905 CYP2C19-substrate:   0.256
CYP2C9-inhibitor:   0.052 CYP2C9-substrate:   0.005
CYP2D6-inhibitor:   0.906 CYP2D6-substrate:   0.046
CYP3A4-inhibitor:   0.599 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.306
HLM stability:   0.996
?
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):  17.575 Half-life (T1/2):  1.156

ADMET: Toxicity

hERG Blockers:  0.238 hERG Blockers (10um):  0.328
Human Hepatotoxicity (H-HT):  0.592 Drug-induced Liver Injury (DILI):  0.349
AMES Toxicity:  0.456 Rat Oral Acute Toxicity:  0.195
Maximum Recommended Daily Dose:  0.909 Skin Sensitization:  0.973
Carcinogencity:  0.907 Eye Corrosion:  0.016
Eye Irritation:  0.813 Respiratory Toxicity:  0.815
Drug-induced Neurotoxicity:  0.197 Ototoxicity:  0.363
Hematotoxicity:  0.527 Drug-induced Nephrotoxicity:  0.263
Genotoxicity:  0.279 RPMI-8226 Immunitoxicity:  0.066
A549 Cytotoxicity:  0.434 Hek293 Cytotoxicity:  0.756
BCF:   1.653
?
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:   3.836
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.274
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.648
?
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
NPO21349 Punica granatum Species Lythraceae Eukaryota n.a. fruit n.a. DOI[10.1007/s00217-007-0799-1]
NPO21349 Punica granatum Species Lythraceae Eukaryota n.a. flower n.a. DOI[10.1016/j.foodchem.2011.01.077]
NPO10830 Dictamnus dasycarpus Species Rutaceae Eukaryota Root barks n.a. n.a. PMID[11473427]
NPO21349 Punica granatum Species Lythraceae Eukaryota n.a. n.a. n.a. PMID[11520216]
NPO21349 Punica granatum Species Lythraceae Eukaryota Seeds n.a. n.a. PMID[15620261]
NPO10830 Dictamnus dasycarpus Species Rutaceae Eukaryota root bark n.a. n.a. PMID[18198838]
NPO2392 Hansenia weberbaueriana Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[25333853]
NPO21349 Punica granatum Species Lythraceae Eukaryota n.a. n.a. n.a. PMID[36560643]
NPO21349 Punica granatum Species Lythraceae Eukaryota n.a. n.a. n.a. PMID[39138188]
NPO21349 Punica granatum Species Lythraceae Eukaryota n.a. n.a. n.a. PMID[39527985]
NPO26976 Bupleurum sibiricum Species Apiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21349 Punica granatum Species Lythraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9662 Conioselinum vaginatum Species Apiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2392 Hansenia weberbaueriana Species Apiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10830 Dictamnus dasycarpus Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21349 Punica granatum Species Lythraceae Eukaryota n.a. n.a. Database[FooDB]
NPO21349 Punica granatum Species Lythraceae Eukaryota Twig n.a. n.a. Database[FooDB]
NPO21349 Punica granatum Species Lythraceae Eukaryota Stem Bark n.a. n.a. Database[FooDB]
NPO21349 Punica granatum Species Lythraceae Eukaryota Seed n.a. n.a. Database[FooDB]
NPO21349 Punica granatum Species Lythraceae Eukaryota Root Bark n.a. n.a. Database[FooDB]
NPO21349 Punica granatum Species Lythraceae Eukaryota Pericarp n.a. n.a. Database[FooDB]
NPO21349 Punica granatum Species Lythraceae Eukaryota Leaf n.a. n.a. Database[FooDB]
NPO21349 Punica granatum Species Lythraceae Eukaryota Fruit n.a. n.a. Database[FooDB]
NPO21349 Punica granatum Species Lythraceae Eukaryota Bark n.a. n.a. Database[FooDB]
NPO21349 Punica granatum Species Lythraceae Eukaryota n.a. n.a. Database[FooDB]
NPO26976 Bupleurum sibiricum Species Apiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO9662 Conioselinum vaginatum Species Apiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO21349 Punica granatum Species Lythraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO10830 Dictamnus dasycarpus Species Rutaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO21349 Punica granatum Species Lythraceae Eukaryota n.a. n.a. Database[Phenol-Explorer]
NPO21349 Punica granatum Species Lythraceae Eukaryota Fruits n.a. Database[Phenol-Explorer]
NPO26976 Bupleurum sibiricum Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO21349 Punica granatum Species Lythraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO9662 Conioselinum vaginatum Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO10830 Dictamnus dasycarpus Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO2392 Hansenia weberbaueriana Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO21349 Punica granatum Species Lythraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO10830 Dictamnus dasycarpus Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO9662 Conioselinum vaginatum Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO10830 Dictamnus dasycarpus Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO2392 Hansenia weberbaueriana Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO21349 Punica granatum Species Lythraceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO26976 Bupleurum sibiricum Species Apiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21349 Punica granatum Species Lythraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10830 Dictamnus dasycarpus Species Rutaceae 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 NPC125091 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 NPC221758
0.8571 High Similarity NPC51014
0.7451 Intermediate Similarity NPC328313
0.7222 Intermediate Similarity NPC472265
0.7222 Intermediate Similarity NPC33913
0.7222 Intermediate Similarity NPC59453
0.7059 Intermediate Similarity NPC162742
0.7059 Intermediate Similarity NPC304309
0.7059 Intermediate Similarity NPC470228
0.6923 Remote Similarity NPC22105
0.6923 Remote Similarity NPC34019
0.6923 Remote Similarity NPC107059
0.6923 Remote Similarity NPC600590
0.6792 Remote Similarity NPC136188
0.6792 Remote Similarity NPC28657
0.6792 Remote Similarity NPC474216
0.6792 Remote Similarity NPC154330
0.6667 Remote Similarity NPC243985
0.6667 Remote Similarity NPC230301
0.6667 Remote Similarity NPC280710
0.6667 Remote Similarity NPC240650
0.6667 Remote Similarity NPC113733
0.6667 Remote Similarity NPC198968
0.6667 Remote Similarity NPC285893
0.6667 Remote Similarity NPC134847
0.6604 Remote Similarity NPC151519
0.6545 Remote Similarity NPC241290
0.6545 Remote Similarity NPC164840
0.6545 Remote Similarity NPC484739
0.6545 Remote Similarity NPC209944
0.6545 Remote Similarity NPC264245
0.6545 Remote Similarity NPC155986
0.65 Remote Similarity NPC601043
0.65 Remote Similarity NPC605412
0.6491 Remote Similarity NPC603646
0.6481 Remote Similarity NPC20688
0.6429 Remote Similarity NPC328714
0.6429 Remote Similarity NPC321381
0.6379 Remote Similarity NPC473943
0.6379 Remote Similarity NPC155011
0.6364 Remote Similarity NPC76879
0.6316 Remote Similarity NPC318495
0.6275 Remote Similarity NPC96319
0.6271 Remote Similarity NPC47761
0.6271 Remote Similarity NPC488870
0.6 Remote Similarity NPC21667
0.6 Remote Similarity NPC474164
0.5763 Remote Similarity NPC1272
0.5763 Remote Similarity NPC470614
0.5667 Remote Similarity NPC477522
0.5606 Remote Similarity NPC309493
0.5385 Remote Similarity NPC5985
0.5373 Remote Similarity NPC235126
0.5373 Remote Similarity NPC242419
0.5333 Remote Similarity NPC26959
0.5312 Remote Similarity NPC474970
0.5312 Remote Similarity NPC474349
0.5312 Remote Similarity NPC474189
0.5294 Remote Similarity NPC147835
0.5294 Remote Similarity NPC253645
0.5294 Remote Similarity NPC85001
0.5294 Remote Similarity NPC95920
0.5231 Remote Similarity NPC176012
0.5217 Remote Similarity NPC486119
0.5185 Remote Similarity NPC320549
0.5185 Remote Similarity NPC156277
0.5185 Remote Similarity NPC58057
0.5185 Remote Similarity NPC151018
0.5161 Remote Similarity NPC58063
0.5085 Remote Similarity NPC98765
0.5082 Remote Similarity NPC31564
0.5082 Remote Similarity NPC87604
0.5082 Remote Similarity NPC145879
0.5079 Remote Similarity NPC268406
0.5075 Remote Similarity NPC91604
0.507 Remote Similarity NPC3715
0.507 Remote Similarity NPC212874

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC125091 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
1.0 High Similarity NPD4786 Phase 1
0.6792 Remote Similarity NPD6942 Phase 4
0.6667 Remote Similarity NPD7339 Approved
0.6604 Remote Similarity NPD3667 Phase 4
0.6275 Remote Similarity NPD3701 Pre-clinical
0.5469 Remote Similarity NPD6399 Phase 3
0.5185 Remote Similarity NPD4808 Phase 2
0.5185 Remote Similarity NPD4809 Phase 4

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