Natural Product: NPC499008

Natural Product IDNPC499008
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Spirostanol
IUPAC Name (1~{R},2~{S},4~{S},6~{R},7~{S},8~{R},9~{S},12~{S},13~{S},16~{S},18~{R})-5',7,9,13-tetramethylspiro[5-oxapentacyclo[10.8.0.0^{2,9}.0^{4,8}.0^{13,18}]icosane-6,2'-tetrahydropyran]-16-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 GMBQZIIUCVWOCD-WMZYJVAFSA-N
Standard InCHI InChI=1S/C27H44O3/c1-16-7-12-27(29-15-16)17(2)24-23(30-27)14-22-20-6-5-18-13-19(28)8-10-25(18,3)21(20)9-11-26(22,24)4/h16-24,28H,5-15H2,1-4H3/t16?,17-,18+,19-,20+,21-,22-,23-,24-,25-,26-,27+/m0/s1
SMILES CC1CC[C@@]2(OC1)O[C@H]1C[C@H]3[C@@H]4CC[C@@H]5C[C@@H](O)CC[C@]5(C)[C@H]4CC[C@]3(C)[C@H]1[C@@H]2C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   416.33 Volume:   450.58
?
Van der Waals volume.
Dense:   0.924 LogP:   5.248
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   4.379
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.75
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   0.0 Rigid Bonds:   30.0
TPSA:   38.69
?
Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   1.0 Rings:   6.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.543 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   5.22 Fsp3:   1.0
MCE-18:   138.667
?
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:   0.656 Fluc inhibitor:   0.002
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.022
?
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:   0.258 Promiscuous compounds:   0.284

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.142 MDCK Permeability:   -4.976
Pgp-inhibitor:   0.9 Pgp-substrate:   0.049
PAMPA:   0.03
?
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%):   0.07 30% Bioavailability (F30%):   0.189
50% Bioavailability (F50%):   0.925

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.072 MRP1:   0.3
Plasma Protein Binding (PPB):   91.737% Volume Distribution (VD):   0.575
Fu: 9.748%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.805
BSEP inhibitor:   0.999

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.039
CYP2C19-inhibitor:   0.026 CYP2C19-substrate:   0.056
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.027
CYP2D6-inhibitor:   0.008 CYP2D6-substrate:   0.097
CYP3A4-inhibitor:   0.992 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.995
HLM stability:   0.795
?
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):  17.785 Half-life (T1/2):  1.593

ADMET: Toxicity

hERG Blockers:  0.185 hERG Blockers (10um):  0.476
Human Hepatotoxicity (H-HT):  0.589 Drug-induced Liver Injury (DILI):  0.323
AMES Toxicity:  0.107 Rat Oral Acute Toxicity:  0.179
Maximum Recommended Daily Dose:  0.75 Skin Sensitization:  0.974
Carcinogencity:  0.694 Eye Corrosion:  0.245
Eye Irritation:  0.857 Respiratory Toxicity:  0.384
Drug-induced Neurotoxicity:  0.028 Ototoxicity:  0.543
Hematotoxicity:  0.069 Drug-induced Nephrotoxicity:  0.212
Genotoxicity:  0.001 RPMI-8226 Immunitoxicity:  0.063
A549 Cytotoxicity:  0.169 Hek293 Cytotoxicity:  0.707
BCF:   2.467
?
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:   3.902
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.784
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.554
?
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
NPO30517 Paris polyphylla Species Melanthiaceae Eukaryota n.a. n.a. n.a. PMID[22663190]
NPO30517 Paris polyphylla Species Melanthiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO30517 Paris polyphylla Species Melanthiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO30517 Paris polyphylla Species Melanthiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]

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 NPC499008 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 NPC248944
1.0 High Similarity NPC7479
1.0 High Similarity NPC257296
0.8 Intermediate Similarity NPC481427
0.7797 Intermediate Similarity NPC296734
0.7627 Intermediate Similarity NPC227260
0.7619 Intermediate Similarity NPC161035
0.7619 Intermediate Similarity NPC170438
0.6613 Remote Similarity NPC24556
0.6406 Remote Similarity NPC273290
0.6406 Remote Similarity NPC232044
0.6389 Remote Similarity NPC144790
0.6389 Remote Similarity NPC149400
0.6389 Remote Similarity NPC88962
0.6364 Remote Similarity NPC305808
0.6351 Remote Similarity NPC473774
0.6351 Remote Similarity NPC481418
0.6351 Remote Similarity NPC481419
0.6351 Remote Similarity NPC481417
0.6324 Remote Similarity NPC235126
0.6324 Remote Similarity NPC242419
0.6301 Remote Similarity NPC277715
0.6267 Remote Similarity NPC24960
0.5775 Remote Similarity NPC177818
0.5732 Remote Similarity NPC473616
0.5679 Remote Similarity NPC131693
0.5679 Remote Similarity NPC485591
0.5679 Remote Similarity NPC475436
0.5556 Remote Similarity NPC297348
0.5556 Remote Similarity NPC325828
0.5556 Remote Similarity NPC249204
0.5556 Remote Similarity NPC48339
0.5556 Remote Similarity NPC177834
0.5556 Remote Similarity NPC141769
0.5556 Remote Similarity NPC477547
0.5542 Remote Similarity NPC312678
0.5542 Remote Similarity NPC253268
0.5488 Remote Similarity NPC234352
0.5479 Remote Similarity NPC486119
0.5422 Remote Similarity NPC477451
0.5362 Remote Similarity NPC155985
0.5362 Remote Similarity NPC601115
0.5357 Remote Similarity NPC250393
0.5316 Remote Similarity NPC481420
0.5316 Remote Similarity NPC481421
0.5301 Remote Similarity NPC294686
0.5294 Remote Similarity NPC206003
0.5294 Remote Similarity NPC473610
0.5244 Remote Similarity NPC481424
0.5244 Remote Similarity NPC481422
0.5244 Remote Similarity NPC481423
0.5233 Remote Similarity NPC211354
0.5233 Remote Similarity NPC107188
0.5233 Remote Similarity NPC19400
0.5211 Remote Similarity NPC187159
0.5176 Remote Similarity NPC222731
0.5172 Remote Similarity NPC264101
0.5114 Remote Similarity NPC107962
0.5067 Remote Similarity NPC100451
0.506 Remote Similarity NPC181845
0.5056 Remote Similarity NPC6295

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC499008 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
1.0 High Similarity NPD6928 Phase 2
0.5584 Remote Similarity NPD7991 Discontinued
0.5556 Remote Similarity NPD8171 Phase 2

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