Natural Product: NPC251929

Natural Product IDNPC251929
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (8S,9R,10R,13S,14R,17E)-17-Ethylidene-10,13-Dimethyl-1,2,6,7,8,9,11,12,14,15-Decahydrocyclopenta[A]Phenanthrene-3,16-Dione
IUPAC Name (8S,9R,10R,13S,14R,17E)-17-ethylidene-10,13-dimethyl-1,2,6,7,8,9,11,12,14,15-decahydrocyclopenta[a]phenanthrene-3,16-dione
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1514005
PubChem CID 16759145
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0000258] Steroids and steroid derivatives
        • [CHEMONTID:0003568] Androstane steroids
          • [CHEMONTID:0001467] Androgens 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 WDXRGPWQVHZTQJ-DWPFYVIESA-N
Standard InCHI InChI=1S/C21H28O2/c1-4-16-19(23)12-18-15-6-5-13-11-14(22)7-9-20(13,2)17(15)8-10-21(16,18)3/h4,11,15,17-18H,5-10,12H2,1-3H3/b16-4-/t15-,17+,18+,20-,21+/m0/s1
SMILES C/C=C1/C(=O)C[C@H]2[C@]1(C)CC[C@@H]1[C@@H]2CCC2=CC(=O)CC[C@]12C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   312.21 Volume:   344.581
?
Van der Waals volume.
Dense:   0.906 LogP:   3.646
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.41
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.646
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The logarithm of aqueous solubility value.
Rotatable Bonds:   0.0 Rigid Bonds:   23.0
TPSA:   34.14
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Topological Polar Surface Area.
 H-Bond Acceptor:   2.0
H-Bond Donor:   0.0 Rings:   4.0
Heavy Atoms:   2.0

MedChem Properties

QED Drug-Likeness Score:   0.61 GASA:   1.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.22 Fsp3:   0.714
MCE-18:   66.667
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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:   0.475 Fluc inhibitor:   0.038
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.012
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.0
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.683 Promiscuous compounds:   0.901

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.502 MDCK Permeability:   -4.795
Pgp-inhibitor:   0.469 Pgp-substrate:   0.107
PAMPA:   0.02
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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%):   0.052 30% Bioavailability (F30%):   0.065
50% Bioavailability (F50%):   0.436

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.551 MRP1:   0.986
Plasma Protein Binding (PPB):   98.262% Volume Distribution (VD):   -0.099
Fu: 1.935%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.644
OATP1B3 inhibitor:   0.9 BCRP inhibitor:   0.126
BSEP inhibitor:   0.973

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.173
CYP2C19-inhibitor:   0.998 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.016 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.015 CYP2D6-substrate:   0.003
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   0.943
CYP2B6-substrate:   0.008 CYP2C8-inhibitor:   0.93
HLM stability:   0.868
?
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):  9.609 Half-life (T1/2):  0.296

ADMET: Toxicity

hERG Blockers:  0.121 hERG Blockers (10um):  0.403
Human Hepatotoxicity (H-HT):  0.674 Drug-induced Liver Injury (DILI):  0.425
AMES Toxicity:  0.36 Rat Oral Acute Toxicity:  0.689
Maximum Recommended Daily Dose:  0.791 Skin Sensitization:  0.793
Carcinogencity:  0.924 Eye Corrosion:  0.014
Eye Irritation:  0.505 Respiratory Toxicity:  0.618
Drug-induced Neurotoxicity:  0.753 Ototoxicity:  0.371
Hematotoxicity:  0.652 Drug-induced Nephrotoxicity:  0.583
Genotoxicity:  0.987 RPMI-8226 Immunitoxicity:  0.145
A549 Cytotoxicity:  0.268 Hek293 Cytotoxicity:  0.608
BCF:   0.858
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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:   3.576
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.066
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.496
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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
NPO13567 Streptomyces sahachiroi Species Streptomycetaceae Bacteria n.a. n.a. n.a. PMID[20485749]
NPO13567 Streptomyces sahachiroi Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO16527 Baptisia minor Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16197 Eucalyptus microcorys Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13567 Streptomyces sahachiroi Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO16197 Eucalyptus microcorys Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16527 Baptisia minor Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13402 Eupatorium inulifolium Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16488 Achromobacter piechaudii Species Alcaligenaceae Bacteria 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
NPT198 Individual protein Vitamin D receptor Homo sapiens Potency n.a. 44668.4 nM PubChem BioAssay data set
NPT93 Individual protein Survival motor neuron protein Homo sapiens Potency = 28183.8 nM PubChem BioAssay data set
NPT51 Individual protein Microtubule-associated protein tau Homo sapiens Potency = 100.0 nM PubChem BioAssay data set

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 NPC251929 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 NPC2634
1.0 High Similarity NPC265782
0.6327 Remote Similarity NPC139397
0.62 Remote Similarity NPC307176
0.62 Remote Similarity NPC321874
0.6154 Remote Similarity NPC282593
0.5849 Remote Similarity NPC214043
0.5849 Remote Similarity NPC227064
0.5849 Remote Similarity NPC85774
0.5849 Remote Similarity NPC329043
0.5849 Remote Similarity NPC58841
0.5849 Remote Similarity NPC161423
0.5818 Remote Similarity NPC303613
0.5741 Remote Similarity NPC35734
0.5741 Remote Similarity NPC144258
0.5741 Remote Similarity NPC159577
0.5741 Remote Similarity NPC115023
0.5741 Remote Similarity NPC327115
0.5741 Remote Similarity NPC602429
0.5636 Remote Similarity NPC149203
0.5636 Remote Similarity NPC237712
0.5536 Remote Similarity NPC249312
0.5536 Remote Similarity NPC323765
0.5439 Remote Similarity NPC310010
0.5439 Remote Similarity NPC326627
0.5172 Remote Similarity NPC119416
0.5082 Remote Similarity NPC320514

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC251929 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 NPD4691 Approved
0.62 Remote Similarity NPD4747 Phase 4
0.5849 Remote Similarity NPD3666 Phase 4
0.5849 Remote Similarity NPD4221 Phase 4
0.5536 Remote Similarity NPD4693 Phase 3
0.5439 Remote Similarity NPD4753 Phase 2
0.5439 Remote Similarity NPD5330 Phase 4
0.5345 Remote Similarity NPD5737 Phase 4
0.5254 Remote Similarity NPD6409 Approved
0.5167 Remote Similarity NPD6672 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