Natural Product: NPC498676

Natural Product IDNPC498676
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 17-[(1~{R})-1,5-dimethylhex-4-enyl]-10,13-dimethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1~{H}-cyclopenta[a]phenanthren-3-ol
IUPAC Name 17-[(1~{R})-1,5-dimethylhex-4-enyl]-10,13-dimethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-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]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0000258] Steroids and steroid derivatives
        • [CHEMONTID:0003566] Cholestane steroids
          • [CHEMONTID:0001469] Cholesterols 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 AVSXSVCZWQODGV-LZHLVKOOSA-N
Standard InCHI InChI=1S/C27H44O/c1-18(2)7-6-8-19(3)23-11-12-24-22-10-9-20-17-21(28)13-15-26(20,4)25(22)14-16-27(23,24)5/h7,9,19,21-25,28H,6,8,10-17H2,1-5H3/t19-,21?,22?,23?,24?,25?,26?,27?/m1/s1
SMILES CC(C)=CCC[C@@H](C)C1CCC2C3CC=C4CC(O)CCC4(C)C3CCC21C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   384.34 Volume:   444.84
?
Van der Waals volume.
Dense:   0.864 LogP:   6.87
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   4.752
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -6.937
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   21.0
TPSA:   20.23
?
Topological Polar Surface Area.
 H-Bond Acceptor:   1.0
H-Bond Donor:   1.0 Rings:   4.0
Heavy Atoms:   1.0

MedChem Properties

QED Drug-Likeness Score:   0.504 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.3 Fsp3:   0.852
MCE-18:   67.6
?
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:   0.912 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.002
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.005
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.556 Promiscuous compounds:   0.023

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.457 MDCK Permeability:   -4.967
Pgp-inhibitor:   0.009 Pgp-substrate:   0.087
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%):   0.008 30% Bioavailability (F30%):   0.074
50% Bioavailability (F50%):   0.995

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.779 MRP1:   0.972
Plasma Protein Binding (PPB):   88.802% Volume Distribution (VD):   -0.019
Fu: 14.126%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.422
OATP1B3 inhibitor:   0.863 BCRP inhibitor:   0.038
BSEP inhibitor:   0.195

ADMET: Metabolism

CYP1A2-inhibitor:   0.001 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.537 CYP2C19-substrate:   0.003
CYP2C9-inhibitor:   0.465 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.215 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.585 CYP3A4-substrate:   0.998
CYP2B6-substrate:   0.014 CYP2C8-inhibitor:   0.767
HLM stability:   0.65
?
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):  16.04 Half-life (T1/2):  0.76

ADMET: Toxicity

hERG Blockers:  0.253 hERG Blockers (10um):  0.652
Human Hepatotoxicity (H-HT):  0.667 Drug-induced Liver Injury (DILI):  0.119
AMES Toxicity:  0.058 Rat Oral Acute Toxicity:  0.08
Maximum Recommended Daily Dose:  0.476 Skin Sensitization:  0.412
Carcinogencity:  0.369 Eye Corrosion:  0.064
Eye Irritation:  0.671 Respiratory Toxicity:  0.707
Drug-induced Neurotoxicity:  0.254 Ototoxicity:  0.776
Hematotoxicity:  0.135 Drug-induced Nephrotoxicity:  0.134
Genotoxicity:  0.0 RPMI-8226 Immunitoxicity:  0.048
A549 Cytotoxicity:  0.358 Hek293 Cytotoxicity:  0.239
BCF:   2.806
?
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:   5.265
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.376
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   6.57
?
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
NPO62381 Galaxaura marginata Species Galaxauraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]

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 NPC498676 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 NPC22105
0.8511 High Similarity NPC162742
0.8511 High Similarity NPC304309
0.8511 High Similarity NPC470228
0.8333 Intermediate Similarity NPC34019
0.8333 Intermediate Similarity NPC107059
0.8163 Intermediate Similarity NPC136188
0.8163 Intermediate Similarity NPC28657
0.8163 Intermediate Similarity NPC474216
0.8 Intermediate Similarity NPC230301
0.8 Intermediate Similarity NPC198968
0.8 Intermediate Similarity NPC285893
0.8 Intermediate Similarity NPC134847
0.7843 Intermediate Similarity NPC241290
0.7843 Intermediate Similarity NPC164840
0.7843 Intermediate Similarity NPC484739
0.7843 Intermediate Similarity NPC209944
0.7843 Intermediate Similarity NPC264245
0.7843 Intermediate Similarity NPC155986
0.7692 Intermediate Similarity NPC321381
0.7547 Intermediate Similarity NPC59453
0.7407 Intermediate Similarity NPC603646
0.7273 Intermediate Similarity NPC473943
0.7255 Intermediate Similarity NPC600590
0.7222 Intermediate Similarity NPC472265
0.7143 Intermediate Similarity NPC488870
0.7115 Intermediate Similarity NPC154330
0.6981 Remote Similarity NPC113733
0.6964 Remote Similarity NPC155011
0.6923 Remote Similarity NPC221758
0.6842 Remote Similarity NPC47761
0.6607 Remote Similarity NPC33913
0.6545 Remote Similarity NPC51014
0.6429 Remote Similarity NPC328714
0.6379 Remote Similarity NPC243985
0.6379 Remote Similarity NPC280710
0.6379 Remote Similarity NPC240650
0.6316 Remote Similarity NPC318495
0.6275 Remote Similarity NPC96319
0.6271 Remote Similarity NPC474164
0.6207 Remote Similarity NPC477522
0.6182 Remote Similarity NPC328313
0.614 Remote Similarity NPC87604
0.5968 Remote Similarity NPC601043
0.5968 Remote Similarity NPC605412
0.5763 Remote Similarity NPC1272
0.5763 Remote Similarity NPC470614
0.5714 Remote Similarity NPC151519
0.5614 Remote Similarity NPC20688
0.5536 Remote Similarity NPC81306
0.5517 Remote Similarity NPC76879
0.541 Remote Similarity NPC474752
0.541 Remote Similarity NPC474683
0.5345 Remote Similarity NPC109546
0.5345 Remote Similarity NPC317458
0.5345 Remote Similarity NPC47982
0.5333 Remote Similarity NPC31564
0.5333 Remote Similarity NPC145879
0.5254 Remote Similarity NPC84694
0.5254 Remote Similarity NPC28862
0.5254 Remote Similarity NPC143182
0.5231 Remote Similarity NPC176012
0.5167 Remote Similarity NPC317927
0.5152 Remote Similarity NPC5985
0.5147 Remote Similarity NPC235126
0.5147 Remote Similarity NPC309493
0.5147 Remote Similarity NPC242419
0.5085 Remote Similarity NPC189972
0.5082 Remote Similarity NPC26959
0.5079 Remote Similarity NPC475789
0.5077 Remote Similarity NPC474970
0.5077 Remote Similarity NPC474349
0.5077 Remote Similarity NPC474189
0.5075 Remote Similarity NPC91604
0.5072 Remote Similarity NPC147835
0.5072 Remote Similarity NPC253645
0.5072 Remote Similarity NPC85001
0.5072 Remote Similarity NPC95920
0.507 Remote Similarity NPC3715

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC498676 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
0.8163 Intermediate Similarity NPD6942 Phase 4
0.8 Intermediate Similarity NPD7339 Approved
0.6923 Remote Similarity NPD4786 Phase 1
0.6275 Remote Similarity NPD3701 Pre-clinical
0.5714 Remote Similarity NPD3667 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