Natural Product: NPC503735

Natural Product IDNPC503735
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 [(3~{S},8~{S},9~{S},10~{R},13~{R},14~{S},16~{S},17~{R})-17-acetyl-3-[(2~{R},3~{R},4~{S},5~{S},6~{R})-4-hydroxy-6-(hydroxymethyl)-3,5-bis[[(2~{S},3~{R},4~{R},5~{R},6~{S})-3,4,5-trihydroxy-6-methyl-tetrahydropyran-2-yl]oxy]tetrahydropyran-2-yl]oxy-10,13-dimethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1~{H}-cyclopenta[a]phenanthren-16-yl] (2~{R},4~{S})-2-methoxy-4-methyl-tetrahydrofuran-2-carboxylate
IUPAC Name [(3~{S},8~{S},9~{S},10~{R},13~{R},14~{S},16~{S},17~{R})-17-acetyl-3-[(2~{R},3~{R},4~{S},5~{S},6~{R})-4-hydroxy-6-(hydroxymethyl)-3,5-bis[[(2~{S},3~{R},4~{R},5~{R},6~{S})-3,4,5-trihydroxy-6-methyl-tetrahydropyran-2-yl]oxy]tetrahydropyran-2-yl]oxy-10,13-dimethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1~{H}-cyclopenta[a]phenanthren-16-yl] (2~{R},4~{S})-2-methoxy-4-methyl-tetrahydrofuran-2-carboxylate
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 DHHHINNFLMEBAG-LHJLCQJFSA-N
Standard InCHI InChI=1S/C46H72O19/c1-19-16-46(57-7,58-18-19)43(56)63-28-15-27-25-9-8-23-14-24(10-12-44(23,5)26(25)11-13-45(27,6)30(28)20(2)48)61-42-39(65-41-36(54)34(52)32(50)22(4)60-41)37(55)38(29(17-47)62-42)64-40-35(53)33(51)31(49)21(3)59-40/h8,19,21-22,24-42,47,49-55H,9-18H2,1-7H3/t19-,21-,22-,24-,25+,26-,27-,28-,29+,30-,31-,32-,33+,34+,35+,36+,37-,38+,39+,40-,41-,42+,44-,45+,46+/m0/s1
SMILES CO[C@]1(C(=O)O[C@H]2C[C@H]3[C@@H]4CC=C5C[C@@H](O[C@@H]6O[C@H](CO)[C@@H](O[C@@H]7O[C@@H](C)[C@H](O)[C@@H](O)[C@H]7O)[C@H](O)[C@H]6O[C@@H]6O[C@@H](C)[C@H](O)[C@@H](O)[C@H]6O)CC[C@]5(C)[C@H]4CC[C@@]3(C)[C@H]2C(C)=O)C[C@H](C)CO1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   928.47 Volume:   894.825
?
Van der Waals volume.
Dense:   1.038 LogP:   1.919
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.716
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.228
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The logarithm of aqueous solubility value.
Rotatable Bonds:   12.0 Rigid Bonds:   45.0
TPSA:   279.05
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Topological Polar Surface Area.
 H-Bond Acceptor:   19.0
H-Bond Donor:   8.0 Rings:   8.0
Heavy Atoms:   19.0

MedChem Properties

QED Drug-Likeness Score:   0.1 GASA:   1.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   6.495 Fsp3:   0.913
MCE-18:   160.818
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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:   0.799 Fluc inhibitor:   0.0
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.004
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.0
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.24 Promiscuous compounds:   0.184

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.265 MDCK Permeability:   -5.15
Pgp-inhibitor:   0.001 Pgp-substrate:   0.964
PAMPA:   0.998
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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%):   0.291 30% Bioavailability (F30%):   0.97
50% Bioavailability (F50%):   0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.253
Plasma Protein Binding (PPB):   58.968% Volume Distribution (VD):   -0.452
Fu: 35.733%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.009
BSEP inhibitor:   0.065

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.546 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.989 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.988
HLM stability:   0.994
?
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):  0.159 Half-life (T1/2):  2.926

ADMET: Toxicity

hERG Blockers:  0.029 hERG Blockers (10um):  0.1
Human Hepatotoxicity (H-HT):  0.357 Drug-induced Liver Injury (DILI):  0.972
AMES Toxicity:  0.941 Rat Oral Acute Toxicity:  0.014
Maximum Recommended Daily Dose:  0.012 Skin Sensitization:  1.0
Carcinogencity:  0.067 Eye Corrosion:  0.0
Eye Irritation:  0.0 Respiratory Toxicity:  0.001
Drug-induced Neurotoxicity:  0.0 Ototoxicity:  0.998
Hematotoxicity:  0.273 Drug-induced Nephrotoxicity:  0.957
Genotoxicity:  0.094 RPMI-8226 Immunitoxicity:  0.208
A549 Cytotoxicity:  0.711 Hek293 Cytotoxicity:  0.664
BCF:   1.085
?
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:   3.553
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.341
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.471
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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
NPO57896 Solanum abutiloides Species Solanaceae 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 NPC503735 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
0.7843 Intermediate Similarity NPC475182
0.7048 Intermediate Similarity NPC470433
0.7048 Intermediate Similarity NPC46190
0.7048 Intermediate Similarity NPC171073
0.6852 Remote Similarity NPC480555
0.6852 Remote Similarity NPC150372
0.6847 Remote Similarity NPC194207
0.6847 Remote Similarity NPC22779
0.6822 Remote Similarity NPC248746
0.6757 Remote Similarity NPC475333
0.6757 Remote Similarity NPC224098
0.6757 Remote Similarity NPC208383
0.6667 Remote Similarity NPC269297
0.6667 Remote Similarity NPC222202
0.6636 Remote Similarity NPC73243
0.6636 Remote Similarity NPC244086
0.6636 Remote Similarity NPC84956
0.6606 Remote Similarity NPC42171
0.6571 Remote Similarity NPC94272
0.6552 Remote Similarity NPC232054
0.6518 Remote Similarity NPC247037
0.6491 Remote Similarity NPC480554
0.64 Remote Similarity NPC165439
0.6379 Remote Similarity NPC480553
0.6348 Remote Similarity NPC249265
0.6293 Remote Similarity NPC23808
0.6293 Remote Similarity NPC87998
0.625 Remote Similarity NPC480556
0.6216 Remote Similarity NPC122819
0.6198 Remote Similarity NPC224314
0.6186 Remote Similarity NPC308140
0.6186 Remote Similarity NPC287885
0.6161 Remote Similarity NPC124677
0.5982 Remote Similarity NPC265275
0.5897 Remote Similarity NPC32361
0.5856 Remote Similarity NPC113044
0.5856 Remote Similarity NPC283829
0.5856 Remote Similarity NPC161676
0.5818 Remote Similarity NPC470432
0.5818 Remote Similarity NPC230507
0.5812 Remote Similarity NPC486386
0.5763 Remote Similarity NPC13193
0.5714 Remote Similarity NPC305423
0.5714 Remote Similarity NPC254255
0.5702 Remote Similarity NPC602423
0.5635 Remote Similarity NPC477808
0.563 Remote Similarity NPC309278
0.5614 Remote Similarity NPC98696
0.5603 Remote Similarity NPC300557
0.5603 Remote Similarity NPC6806
0.5508 Remote Similarity NPC102016
0.5508 Remote Similarity NPC95051
0.5405 Remote Similarity NPC19400
0.5385 Remote Similarity NPC477809
0.5304 Remote Similarity NPC14704
0.5285 Remote Similarity NPC218571
0.5285 Remote Similarity NPC487615
0.5263 Remote Similarity NPC485595
0.5263 Remote Similarity NPC6295
0.5214 Remote Similarity NPC486388
0.5172 Remote Similarity NPC470748
0.5138 Remote Similarity NPC181845
0.513 Remote Similarity NPC15249
0.513 Remote Similarity NPC306991
0.513 Remote Similarity NPC25455
0.5093 Remote Similarity NPC486114
0.5085 Remote Similarity NPC40440
0.5041 Remote Similarity NPC475550

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC503735 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
0.6216 Remote Similarity NPD8449 Approved

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