Natural Product: NPC498201

Natural Product IDNPC498201
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 NS00093824
IUPAC Name (3~{S},5~{S},10~{S},11~{R},13~{R},14~{S},17~{R})-5,11,14-trihydroxy-13-methyl-17-(5-oxo-2~{H}-furan-3-yl)-3-[(2~{S},5~{S})-3,4,5-trihydroxy-6-methyl-tetrahydropyran-2-yl]oxy-2,3,4,6,7,8,9,11,12,15,16,17-dodecahydro-1~{H}-cyclopenta[a]phenanthrene-10-carbaldehyde
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 AZOXLPPOBHVORY-MEYXTMGPSA-N
Standard InCHI InChI=1S/C29H42O11/c1-14-22(33)23(34)24(35)25(39-14)40-16-3-6-27(13-30)21-18(4-7-28(27,36)10-16)29(37)8-5-17(15-9-20(32)38-12-15)26(29,2)11-19(21)31/h9,13-14,16-19,21-25,31,33-37H,3-8,10-12H2,1-2H3/t14?,16-,17+,18?,19+,21?,22+,23?,24?,25+,26+,27-,28-,29-/m0/s1
SMILES CC1O[C@H](O[C@H]2CC[C@]3(C=O)C4C(CC[C@]3(O)C2)[C@@]2(O)CC[C@H](C3=CC(=O)OC3)[C@@]2(C)C[C@H]4O)C(O)C(O)[C@@H]1O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   566.27 Volume:   547.584
?
Van der Waals volume.
Dense:   1.034 LogP:   -0.529
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   0.262
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.155
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   33.0
TPSA:   183.21
?
Topological Polar Surface Area.
 H-Bond Acceptor:   11.0
H-Bond Donor:   6.0 Rings:   6.0
Heavy Atoms:   11.0

MedChem Properties

QED Drug-Likeness Score:   0.149 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   5.511 Fsp3:   0.862
MCE-18:   119.778
?
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:   0.384 Fluc inhibitor:   0.003
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.023
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.004
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.07 Promiscuous compounds:   0.029

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.422 MDCK Permeability:   -5.241
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):   0.351
20% Bioavailability (F20%):   0.97 30% Bioavailability (F30%):   0.953
50% Bioavailability (F50%):   0.998

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.002 MRP1:   0.845
Plasma Protein Binding (PPB):   39.664% Volume Distribution (VD):   -0.34
Fu: 62.402%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.56
OATP1B3 inhibitor:   0.731 BCRP inhibitor:   0.014
BSEP inhibitor:   0.061

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:   0.001 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.02
HLM stability:   0.0
?
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):  2.008 Half-life (T1/2):  3.827

ADMET: Toxicity

hERG Blockers:  0.033 hERG Blockers (10um):  0.247
Human Hepatotoxicity (H-HT):  0.79 Drug-induced Liver Injury (DILI):  0.287
AMES Toxicity:  0.931 Rat Oral Acute Toxicity:  0.858
Maximum Recommended Daily Dose:  0.991 Skin Sensitization:  1.0
Carcinogencity:  0.915 Eye Corrosion:  0.0
Eye Irritation:  0.001 Respiratory Toxicity:  0.569
Drug-induced Neurotoxicity:  0.036 Ototoxicity:  0.928
Hematotoxicity:  0.356 Drug-induced Nephrotoxicity:  0.886
Genotoxicity:  0.995 RPMI-8226 Immunitoxicity:  0.459
A549 Cytotoxicity:  0.52 Hek293 Cytotoxicity:  0.827
BCF:   0.43
?
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:   3.212
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.077
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.048
?
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
NPO44527 Ornithogalum nutans L. Genus Hyacinthaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO57834 Ornithogalum pyrenaicum L. Genus Hyacinthaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO44199 Ornithogalum umbellatum L. Genus Hyacinthaceae 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 NPC498201 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
0.8421 Intermediate Similarity NPC17896
0.8421 Intermediate Similarity NPC469755
0.8421 Intermediate Similarity NPC284406
0.8421 Intermediate Similarity NPC197707
0.8421 Intermediate Similarity NPC251866
0.7976 Intermediate Similarity NPC59288
0.7468 Intermediate Similarity NPC99728
0.7468 Intermediate Similarity NPC87250
0.7468 Intermediate Similarity NPC244402
0.7468 Intermediate Similarity NPC50305
0.7439 Intermediate Similarity NPC9499
0.7439 Intermediate Similarity NPC471360
0.7439 Intermediate Similarity NPC469751
0.7439 Intermediate Similarity NPC471361
0.7439 Intermediate Similarity NPC86159
0.7439 Intermediate Similarity NPC469752
0.7439 Intermediate Similarity NPC469754
0.7439 Intermediate Similarity NPC70542
0.7317 Intermediate Similarity NPC83287
0.7284 Intermediate Similarity NPC157376
0.7284 Intermediate Similarity NPC142066
0.7284 Intermediate Similarity NPC603972
0.6951 Remote Similarity NPC219085
0.6889 Remote Similarity NPC469749
0.6747 Remote Similarity NPC309034
0.6742 Remote Similarity NPC32793
0.6742 Remote Similarity NPC116075
0.6706 Remote Similarity NPC77319
0.6706 Remote Similarity NPC471351
0.6706 Remote Similarity NPC471355
0.6667 Remote Similarity NPC469750
0.6667 Remote Similarity NPC264336
0.6548 Remote Similarity NPC84987
0.6429 Remote Similarity NPC99620
0.6395 Remote Similarity NPC10823
0.6364 Remote Similarity NPC471354
0.6364 Remote Similarity NPC27507
0.6277 Remote Similarity NPC146857
0.6277 Remote Similarity NPC247190
0.6207 Remote Similarity NPC76572
0.6207 Remote Similarity NPC193382
0.6136 Remote Similarity NPC180079
0.6118 Remote Similarity NPC158344
0.6092 Remote Similarity NPC6108
0.6092 Remote Similarity NPC89514
0.6092 Remote Similarity NPC484210
0.6022 Remote Similarity NPC608063
0.593 Remote Similarity NPC474418
0.5909 Remote Similarity NPC480915
0.5889 Remote Similarity NPC471359
0.5889 Remote Similarity NPC179412
0.5889 Remote Similarity NPC471356
0.5843 Remote Similarity NPC480914
0.5842 Remote Similarity NPC329675
0.5842 Remote Similarity NPC194716
0.5795 Remote Similarity NPC196429
0.5789 Remote Similarity NPC475629
0.573 Remote Similarity NPC5311
0.5684 Remote Similarity NPC475556
0.5684 Remote Similarity NPC240070
0.5684 Remote Similarity NPC311706
0.5652 Remote Similarity NPC469753
0.5579 Remote Similarity NPC27363
0.5556 Remote Similarity NPC77299
0.5556 Remote Similarity NPC480906
0.5543 Remote Similarity NPC471353
0.5444 Remote Similarity NPC484211
0.5392 Remote Similarity NPC329636
0.5385 Remote Similarity NPC34390
0.5361 Remote Similarity NPC188234
0.5361 Remote Similarity NPC471357
0.5361 Remote Similarity NPC469757
0.5361 Remote Similarity NPC117702
0.5312 Remote Similarity NPC30483
0.5312 Remote Similarity NPC470897
0.5263 Remote Similarity NPC480907
0.5258 Remote Similarity NPC236973
0.52 Remote Similarity NPC232785
0.52 Remote Similarity NPC486139
0.5181 Remote Similarity NPC72772
0.5165 Remote Similarity NPC471633
0.5106 Remote Similarity NPC250556
0.5102 Remote Similarity NPC32177
0.5102 Remote Similarity NPC292467
0.5102 Remote Similarity NPC469756
0.5102 Remote Similarity NPC275901
0.51 Remote Similarity NPC486143
0.51 Remote Similarity NPC125077
0.51 Remote Similarity NPC486142
0.51 Remote Similarity NPC486149
0.5098 Remote Similarity NPC486138
0.5098 Remote Similarity NPC276838
0.5051 Remote Similarity NPC480910
0.5051 Remote Similarity NPC480909

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC498201 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
0.8421 Intermediate Similarity NPD7319 Approved
0.7317 Intermediate Similarity NPD7327 Approved
0.7317 Intermediate Similarity NPD7328 Phase 4
0.5106 Remote Similarity NPD7507 Pre-clinical

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