Natural Product: NPC185936

Natural Product IDNPC185936
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (8S,10R,11S,13S,14S,17S)-11-Hydroxy-17-(2-Hydroxyacetyl)-10,13-Dimethyl-1,2,6,7,8,9,11,12,14,15,16,17-Dodecahydrocyclopenta[A]Phenanthren-3-One
IUPAC Name (8S,10R,11S,13S,14S,17S)-11-hydroxy-17-(2-hydroxyacetyl)-10,13-dimethyl-1,2,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-3-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1513569
PubChem CID 16758819
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0000258] Steroids and steroid derivatives
        • [CHEMONTID:0001295] Hydroxysteroids
          • [CHEMONTID:0003095] 21-hydroxysteroids

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 OMFXVFTZEKFJBZ-KRGAXNBZSA-N
Standard InCHI InChI=1S/C21H30O4/c1-20-8-7-13(23)9-12(20)3-4-14-15-5-6-16(18(25)11-22)21(15,2)10-17(24)19(14)20/h9,14-17,19,22,24H,3-8,10-11H2,1-2H3/t14-,15-,16+,17-,19?,20-,21-/m0/s1
SMILES OCC(=O)[C@H]1CC[C@@H]2[C@]1(C)C[C@H](O)C1[C@H]2CCC2=CC(=O)CC[C@]12C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   346.21 Volume:   364.798
?
Van der Waals volume.
Dense:   0.949 LogP:   2.125
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.039
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.31
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   22.0
TPSA:   74.6
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   2.0 Rings:   4.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.806 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.323 Fsp3:   0.81
MCE-18:   71.158
?
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:   0.232 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.016
?
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:   0.265 Promiscuous compounds:   0.988

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.36 MDCK Permeability:   -4.781
Pgp-inhibitor:   0.108 Pgp-substrate:   0.527
PAMPA:   0.7
?
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):   0.001
20% Bioavailability (F20%):   0.141 30% Bioavailability (F30%):   0.025
50% Bioavailability (F50%):   0.27

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.742 MRP1:   0.772
Plasma Protein Binding (PPB):   87.712% Volume Distribution (VD):   -0.329
Fu: 11.411%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.028
OATP1B3 inhibitor:   0.333 BCRP inhibitor:   0.008
BSEP inhibitor:   0.865

ADMET: Metabolism

CYP1A2-inhibitor:   0.003 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.002 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.002 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.001
CYP3A4-inhibitor:   0.959 CYP3A4-substrate:   0.662
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.416
HLM stability:   0.606
?
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):  10.458 Half-life (T1/2):  1.539

ADMET: Toxicity

hERG Blockers:  0.076 hERG Blockers (10um):  0.39
Human Hepatotoxicity (H-HT):  0.634 Drug-induced Liver Injury (DILI):  0.25
AMES Toxicity:  0.526 Rat Oral Acute Toxicity:  0.379
Maximum Recommended Daily Dose:  0.637 Skin Sensitization:  0.927
Carcinogencity:  0.845 Eye Corrosion:  0.01
Eye Irritation:  0.423 Respiratory Toxicity:  0.576
Drug-induced Neurotoxicity:  0.51 Ototoxicity:  0.518
Hematotoxicity:  0.432 Drug-induced Nephrotoxicity:  0.31
Genotoxicity:  0.869 RPMI-8226 Immunitoxicity:  0.1
A549 Cytotoxicity:  0.164 Hek293 Cytotoxicity:  0.439
BCF:   0.539
?
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:   3.191
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.616
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.871
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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
NPO9165 Asclepias curassavica Species Apocynaceae Eukaryota n.a. n.a. n.a. PMID[16252914]
NPO9165 Asclepias curassavica Species Apocynaceae Eukaryota n.a. n.a. n.a. PMID[19251412]
NPO12323 Bos taurus Species Bovidae Eukaryota n.a. n.a. n.a. PMID[24211545]
NPO9165 Asclepias curassavica Species Apocynaceae Eukaryota n.a. n.a. n.a. PMID[37375900]
NPO12323 Bos taurus Species Bovidae Eukaryota Urine n.a. n.a. PMID[6330305]
NPO12323 Bos taurus Species Bovidae Eukaryota n.a. n.a. n.a. PMID[932730]
NPO9165 Asclepias curassavica Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17393 Bubalus bubalis Species Bovidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12323 Bos taurus Species Bovidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12323 Bos taurus Species Bovidae Eukaryota n.a. n.a. Database[FooDB]
NPO12323 Bos taurus Species Bovidae Eukaryota n.a. n.a. Database[FooDB]
NPO12323 Bos taurus Species Bovidae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO17393 Bubalus bubalis Species Bovidae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO9165 Asclepias curassavica Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO9165 Asclepias curassavica Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO17393 Bubalus bubalis Species Bovidae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO12323 Bos taurus Species Bovidae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO12323 Bos taurus Species Bovidae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO17393 Bubalus bubalis Species Bovidae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO12323 Bos taurus Species Bovidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9165 Asclepias curassavica Species Apocynaceae 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
NPT483 Individual protein Prelamin-A/C Homo sapiens Potency = 25118.9 nM PubChem BioAssay data set
NPT58 Individual protein Bloom syndrome protein Homo sapiens Potency = 89125.1 nM PubChem BioAssay data set
NPT93 Individual protein Survival motor neuron protein Homo sapiens Potency = 7943.3 nM PubChem BioAssay data set
NPT51 Individual protein Microtubule-associated protein tau Homo sapiens Potency = 125.9 nM PubChem BioAssay data set
NPT5 Individual protein Histone-lysine N-methyltransferase, H3 lysine-9 specific 3 Homo sapiens Potency n.a. 22.4 nM PubChem BioAssay data set
NPT49 Individual protein DNA-(apurinic or apyrimidinic site) lyase Homo sapiens Potency n.a. 8912.5 nM PubChem BioAssay data set

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT6 Organism Plasmodium falciparum Plasmodium falciparum Potency n.a. 18526.0 nM PubChem BioAssay data set

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 NPC185936 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 NPC168027
0.86 High Similarity NPC328539
0.7818 Intermediate Similarity NPC192428
0.7222 Intermediate Similarity NPC237712
0.6429 Remote Similarity NPC257176
0.6333 Remote Similarity NPC18509
0.6333 Remote Similarity NPC319582
0.5714 Remote Similarity NPC307176
0.5714 Remote Similarity NPC321874
0.569 Remote Similarity NPC214043
0.569 Remote Similarity NPC85774
0.5362 Remote Similarity NPC478926

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC185936 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
0.7818 Intermediate Similarity NPD4697 Phase 2
0.6429 Remote Similarity NPD3618 Phase 1
0.6333 Remote Similarity NPD4754 Approved
0.6333 Remote Similarity NPD4755 Phase 4
0.5932 Remote Similarity NPD5328 Phase 4
0.5909 Remote Similarity NPD6401 Phase 2
0.5909 Remote Similarity NPD6402 Phase 4
0.5735 Remote Similarity NPD6675 Phase 4
0.5714 Remote Similarity NPD4747 Phase 4
0.5606 Remote Similarity NPD5739 Phase 4
0.5441 Remote Similarity NPD4767 Approved
0.5362 Remote Similarity NPD4768 Phase 4
0.5238 Remote Similarity NPD5737 Phase 4
0.5211 Remote Similarity NPD7128 Phase 4
0.5139 Remote Similarity NPD7320 Phase 4
0.5077 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