Natural Product: NPC504805

Natural Product IDNPC504805
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (3~{S},5~{S},8~{R},9~{S},10~{R},13~{S},14~{S},17~{R})-17-[(1~{S},2~{S},4~{R})-2-hydroxy-1,4,5-trimethyl-hexyl]-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1~{H}-cyclopenta[a]phenanthren-3-ol
IUPAC Name (3~{S},5~{S},8~{R},9~{S},10~{R},13~{S},14~{S},17~{R})-17-[(1~{S},2~{S},4~{R})-2-hydroxy-1,4,5-trimethyl-hexyl]-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1~{H}-cyclopenta[a]phenanthren-3-ol
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]

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 ZHZKWZJLUNXOSN-NBHJCTFBSA-N
Standard InCHI InChI=1S/C28H50O2/c1-17(2)18(3)15-26(30)19(4)23-9-10-24-22-8-7-20-16-21(29)11-13-27(20,5)25(22)12-14-28(23,24)6/h17-26,29-30H,7-16H2,1-6H3/t18-,19+,20+,21+,22+,23-,24+,25+,26+,27-,28-/m1/s1
SMILES CC(C)[C@H](C)C[C@H](O)[C@@H](C)[C@H]1CC[C@H]2[C@@H]3CC[C@H]4C[C@@H](O)CC[C@@]4(C)[C@H]3CC[C@]12C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   418.38 Volume:   476.199
?
Van der Waals volume.
Dense:   0.879 LogP:   6.323
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   4.693
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.635
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   20.0
TPSA:   40.46
?
Topological Polar Surface Area.
 H-Bond Acceptor:   2.0
H-Bond Donor:   2.0 Rings:   4.0
Heavy Atoms:   2.0

MedChem Properties

QED Drug-Likeness Score:   0.522 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.563 Fsp3:   1.0
MCE-18:   73.0
?
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:   0.693 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.021
?
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:   0.579 Promiscuous compounds:   0.054

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.255 MDCK Permeability:   -5.112
Pgp-inhibitor:   0.533 Pgp-substrate:   0.134
PAMPA:   0.078
?
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%):   0.031 30% Bioavailability (F30%):   0.068
50% Bioavailability (F50%):   0.943

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.003 MRP1:   0.167
Plasma Protein Binding (PPB):   69.025% Volume Distribution (VD):   -0.063
Fu: 32.156%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   0.987 BCRP inhibitor:   0.086
BSEP inhibitor:   0.895

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.001
CYP2C19-inhibitor:   0.203 CYP2C19-substrate:   0.009
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.081
CYP2D6-inhibitor:   0.005 CYP2D6-substrate:   0.191
CYP3A4-inhibitor:   0.999 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.989
HLM stability:   0.844
?
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):  16.106 Half-life (T1/2):  1.466

ADMET: Toxicity

hERG Blockers:  0.062 hERG Blockers (10um):  0.11
Human Hepatotoxicity (H-HT):  0.42 Drug-induced Liver Injury (DILI):  0.147
AMES Toxicity:  0.385 Rat Oral Acute Toxicity:  0.02
Maximum Recommended Daily Dose:  0.499 Skin Sensitization:  0.99
Carcinogencity:  0.913 Eye Corrosion:  0.381
Eye Irritation:  0.962 Respiratory Toxicity:  0.855
Drug-induced Neurotoxicity:  0.006 Ototoxicity:  0.798
Hematotoxicity:  0.62 Drug-induced Nephrotoxicity:  0.935
Genotoxicity:  0.0 RPMI-8226 Immunitoxicity:  0.047
A549 Cytotoxicity:  0.778 Hek293 Cytotoxicity:  0.754
BCF:   2.75
?
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:   4.466
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.327
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.16
?
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
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. DOI[10.1016/S0014-5793(03)00033-4]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. DOI[10.1021/ac991142i]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. DOI[10.1034/j.1399-3054.2003.00030.x]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. DOI[10.1046/j.1365-3040.2001.00686.x]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. DOI[10.1074/jbc.274.1.397]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. DOI[10.1074/jbc.M302362200]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. DOI[10.1074/jbc.M314195200]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. DOI[10.1074/jbc.M411109200]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. DOI[10.1104/pp.103.022368]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[10952545]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. leaf n.a. PMID[10952545]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[11005203]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[12637544]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[12805618]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[14745019]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[15280363]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[15820655]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[15834012]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota aerial parts n.a. n.a. PMID[15844959]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[1684022]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[17611796]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[18057039]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[18235971]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[18318836]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. leaf n.a. PMID[19521717]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[21193570]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[21194489]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[21395888]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[21800258]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[23370715]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[23950498]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. root n.a. PMID[24163311]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[24285094]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. root n.a. PMID[25457500]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. root n.a. PMID[27363486]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[27432888]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[8278506]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. Database[Article]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. root n.a. Database[MetaboLights]
NPO19866 Arabidopsis thaliana Species Brassicaceae Eukaryota n.a. n.a. n.a. Database[MetaboLights]
NPO19866 Arabidopsis thaliana Species Brassicaceae 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 NPC504805 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
0.7174 Intermediate Similarity NPC148174
0.6957 Remote Similarity NPC71460
0.6957 Remote Similarity NPC218585
0.6818 Remote Similarity NPC114891
0.6383 Remote Similarity NPC320549
0.6383 Remote Similarity NPC156277
0.6383 Remote Similarity NPC58057
0.6383 Remote Similarity NPC151018
0.6154 Remote Similarity NPC167702
0.6154 Remote Similarity NPC280026
0.6 Remote Similarity NPC254340
0.5957 Remote Similarity NPC281540
0.5957 Remote Similarity NPC159654
0.5957 Remote Similarity NPC167995
0.5957 Remote Similarity NPC118937
0.5849 Remote Similarity NPC192456
0.5517 Remote Similarity NPC323180
0.549 Remote Similarity NPC327728
0.549 Remote Similarity NPC6120
0.549 Remote Similarity NPC131892
0.549 Remote Similarity NPC213178
0.549 Remote Similarity NPC103822
0.5246 Remote Similarity NPC320478
0.52 Remote Similarity NPC111234

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC504805 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
0.6383 Remote Similarity NPD4808 Phase 2
0.6383 Remote Similarity NPD4809 Phase 4
0.6154 Remote Similarity NPD6113 Clinical (unspecified phase)
0.549 Remote Similarity NPD3699 Clinical (unspecified phase)
0.549 Remote Similarity NPD3700 Clinical (unspecified phase)
0.5385 Remote Similarity NPD4787 Phase 1
0.5091 Remote Similarity NPD3671 Phase 1

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