Natural Product: NPC498892

Natural Product IDNPC498892
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Erysimosol
IUPAC Name 3-[(3~{S},5~{S},10~{R},13~{R},14~{S},17~{R})-3-[(2~{R},5~{S})-6-[[(3~{R},6~{S})-4,6-dihydroxy-2-methyl-tetrahydropyran-3-yl]oxymethyl]-3,4,5-trihydroxy-tetrahydropyran-2-yl]oxy-5,14-dihydroxy-10-(hydroxymethyl)-13-methyl-2,3,4,6,7,8,9,11,12,15,16,17-dodecahydro-1~{H}-cyclopenta[a]phenanthren-17-yl]-2~{H}-furan-5-one
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 FWXUQGTVECLNCB-OKDYQEHCSA-N
Standard InCHI InChI=1S/C35H54O14/c1-17-30(23(37)12-26(39)47-17)46-15-24-27(40)28(41)29(42)31(49-24)48-19-3-8-33(16-36)21-4-7-32(2)20(18-11-25(38)45-14-18)6-10-35(32,44)22(21)5-9-34(33,43)13-19/h11,17,19-24,26-31,36-37,39-44H,3-10,12-16H2,1-2H3/t17?,19-,20+,21?,22?,23?,24?,26-,27+,28?,29?,30-,31+,32+,33-,34-,35-/m0/s1
SMILES CC1O[C@H](O)CC(O)[C@H]1OCC1O[C@@H](O[C@H]2CC[C@]3(CO)C4CC[C@]5(C)[C@@H](C6=CC(=O)OC6)CC[C@]5(O)C4CC[C@]3(O)C2)C(O)C(O)[C@@H]1O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   698.35 Volume:   671.811
?
Van der Waals volume.
Dense:   1.04 LogP:   -0.28
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   0.475
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -1.986
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   7.0 Rigid Bonds:   38.0
TPSA:   225.06
?
Topological Polar Surface Area.
 H-Bond Acceptor:   14.0
H-Bond Donor:   8.0 Rings:   7.0
Heavy Atoms:   14.0

MedChem Properties

QED Drug-Likeness Score:   0.123 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   5.875 Fsp3:   0.914
MCE-18:   136.119
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Accepted
Pfizer Rule:   Rejected GSK Rule:   Accepted
Golden Triangle Rule:   Accepted BMS Rule:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.344 Fluc inhibitor:   0.001
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.019
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.002
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.075 Promiscuous compounds:   0.054

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.743 MDCK Permeability:   -5.232
Pgp-inhibitor:   0.0 Pgp-substrate:   1.0
PAMPA:   1.0
?
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):   0.017
20% Bioavailability (F20%):   0.98 30% Bioavailability (F30%):   0.808
50% Bioavailability (F50%):   0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.961
Plasma Protein Binding (PPB):   53.018% Volume Distribution (VD):   -0.428
Fu: 48.451%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.543
OATP1B3 inhibitor:   0.122 BCRP inhibitor:   0.012
BSEP inhibitor:   0.112

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.459 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.953
HLM stability:   0.002
?
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):  0.743 Half-life (T1/2):  3.71

ADMET: Toxicity

hERG Blockers:  0.218 hERG Blockers (10um):  0.801
Human Hepatotoxicity (H-HT):  0.912 Drug-induced Liver Injury (DILI):  0.875
AMES Toxicity:  0.89 Rat Oral Acute Toxicity:  0.99
Maximum Recommended Daily Dose:  1.0 Skin Sensitization:  1.0
Carcinogencity:  0.901 Eye Corrosion:  0.0
Eye Irritation:  0.0 Respiratory Toxicity:  0.977
Drug-induced Neurotoxicity:  0.029 Ototoxicity:  0.964
Hematotoxicity:  0.089 Drug-induced Nephrotoxicity:  0.943
Genotoxicity:  1.0 RPMI-8226 Immunitoxicity:  0.856
A549 Cytotoxicity:  0.936 Hek293 Cytotoxicity:  0.997
BCF:   0.458
?
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:   3.324
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.218
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.04
?
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
NPO54515 Erysimum cheiranthoides L. Genus Brassicaceae 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 NPC498892 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
0.7558 Intermediate Similarity NPC157376
0.7558 Intermediate Similarity NPC142066
0.7558 Intermediate Similarity NPC603972
0.6667 Remote Similarity NPC84987
0.6556 Remote Similarity NPC99728
0.6556 Remote Similarity NPC87250
0.6556 Remote Similarity NPC244402
0.6556 Remote Similarity NPC50305
0.6413 Remote Similarity NPC17896
0.6413 Remote Similarity NPC469755
0.6413 Remote Similarity NPC284406
0.6413 Remote Similarity NPC197707
0.6413 Remote Similarity NPC251866
0.6327 Remote Similarity NPC32793
0.6327 Remote Similarity NPC116075
0.6316 Remote Similarity NPC471354
0.6316 Remote Similarity NPC27507
0.6264 Remote Similarity NPC158344
0.6263 Remote Similarity NPC264336
0.6263 Remote Similarity NPC475629
0.6162 Remote Similarity NPC475556
0.6162 Remote Similarity NPC311706
0.6129 Remote Similarity NPC219085
0.5981 Remote Similarity NPC194716
0.596 Remote Similarity NPC30483
0.596 Remote Similarity NPC470897
0.5895 Remote Similarity NPC77299
0.5895 Remote Similarity NPC480906
0.5849 Remote Similarity NPC486136
0.5833 Remote Similarity NPC76572
0.5833 Remote Similarity NPC193382
0.5825 Remote Similarity NPC469749
0.5769 Remote Similarity NPC146857
0.5743 Remote Similarity NPC32177
0.5743 Remote Similarity NPC469756
0.5743 Remote Similarity NPC275901
0.5729 Remote Similarity NPC5311
0.5701 Remote Similarity NPC486144
0.5701 Remote Similarity NPC486145
0.5701 Remote Similarity NPC486147
0.5701 Remote Similarity NPC486148
0.5686 Remote Similarity NPC608063
0.5684 Remote Similarity NPC99620
0.567 Remote Similarity NPC480914
0.5619 Remote Similarity NPC247190
0.5612 Remote Similarity NPC77319
0.5612 Remote Similarity NPC471351
0.5612 Remote Similarity NPC471355
0.5588 Remote Similarity NPC236973
0.5579 Remote Similarity NPC474418
0.5577 Remote Similarity NPC59288
0.5577 Remote Similarity NPC486135
0.5577 Remote Similarity NPC486137
0.5567 Remote Similarity NPC469750
0.5556 Remote Similarity NPC475590
0.5545 Remote Similarity NPC329675
0.5534 Remote Similarity NPC188234
0.5464 Remote Similarity NPC309034
0.5446 Remote Similarity NPC480907
0.5429 Remote Similarity NPC486143
0.5429 Remote Similarity NPC486142
0.5429 Remote Similarity NPC486149
0.54 Remote Similarity NPC9499
0.54 Remote Similarity NPC471360
0.54 Remote Similarity NPC469751
0.54 Remote Similarity NPC471361
0.54 Remote Similarity NPC86159
0.54 Remote Similarity NPC469752
0.54 Remote Similarity NPC469754
0.54 Remote Similarity NPC70542
0.5385 Remote Similarity NPC480910
0.5385 Remote Similarity NPC480909
0.5377 Remote Similarity NPC232785
0.5377 Remote Similarity NPC486139
0.537 Remote Similarity NPC486131
0.5357 Remote Similarity NPC486133
0.5333 Remote Similarity NPC610296
0.5321 Remote Similarity NPC486128
0.5315 Remote Similarity NPC475419
0.5306 Remote Similarity NPC196429
0.53 Remote Similarity NPC83287
0.5283 Remote Similarity NPC125077
0.5281 Remote Similarity NPC10232
0.5268 Remote Similarity NPC474908
0.5268 Remote Similarity NPC486134
0.5268 Remote Similarity NPC486141
0.5263 Remote Similarity NPC474423
0.5253 Remote Similarity NPC6108
0.5253 Remote Similarity NPC89514
0.5253 Remote Similarity NPC34390
0.5238 Remote Similarity NPC240070
0.5221 Remote Similarity NPC486150
0.52 Remote Similarity NPC243196
0.52 Remote Similarity NPC10823
0.5149 Remote Similarity NPC146456
0.5149 Remote Similarity NPC180079
0.5143 Remote Similarity NPC292467
0.5094 Remote Similarity NPC486130
0.5091 Remote Similarity NPC486132
0.5047 Remote Similarity NPC486127
0.5046 Remote Similarity NPC329986
0.5046 Remote Similarity NPC140092
0.5046 Remote Similarity NPC486146

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC498892 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
0.6413 Remote Similarity NPD7319 Approved
0.53 Remote Similarity NPD7327 Approved
0.53 Remote Similarity NPD7328 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