Natural Product: NPC257726

Natural Product IDNPC257726
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 12-Deacetoxyscalarin 19-Acetate
IUPAC Name [(1R,5aS,5bR,7aS,11aS,11bR,13aS,13bR)-5b,8,8,11a,13a-pentamethyl-3-oxo-5,5a,6,7,7a,9,10,11,11b,12,13,13b-dodecahydro-1H-phenanthro[1,2-g][2]benzofuran-1-yl] acetate
Synonyms 12-Deacetoxyscalarin 19-Acetate
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL519647
PubChem CID 3012493
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0000259] Prenol lipids
        • [CHEMONTID:0001552] Sesterterpenoids
          • [CHEMONTID:0002883] Scalarane sesterterpenoids

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 FWKSHXYKUMEBJI-YCHJHXPOSA-N
Standard InCHI InChI=1S/C27H40O4/c1-16(28)30-23-21-17(22(29)31-23)8-9-19-26(5)14-10-18-24(2,3)12-7-13-25(18,4)20(26)11-15-27(19,21)6/h8,18-21,23H,7,9-15H2,1-6H3/t18-,19-,20+,21+,23+,25-,26-,27-/m0/s1
SMILES CC(=O)O[C@@H]1OC(=O)C2=CC[C@@H]3[C@]([C@@H]12)(C)CC[C@H]1[C@@]3(C)CC[C@@H]2[C@]1(C)CCCC2(C)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   428.29 Volume:   460.017
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Van der Waals volume.
Dense:   0.931 LogP:   4.319
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.805
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -6.331
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The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   27.0
TPSA:   52.6
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Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   0.0 Rings:   5.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.478 GASA:   1.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.702 Fsp3:   0.852
MCE-18:   93.8
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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:   0.453 Fluc inhibitor:   0.315
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.006
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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:   0.453 Promiscuous compounds:   0.338

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.604 MDCK Permeability:   -4.653
Pgp-inhibitor:   0.855 Pgp-substrate:   0.0
PAMPA:   0.042
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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):   0.001
20% Bioavailability (F20%):   0.033 30% Bioavailability (F30%):   0.154
50% Bioavailability (F50%):   0.921

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.447 MRP1:   0.615
Plasma Protein Binding (PPB):   96.069% Volume Distribution (VD):   0.034
Fu: 5.012%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   0.659
BSEP inhibitor:   0.966

ADMET: Metabolism

CYP1A2-inhibitor:   0.002 CYP1A2-substrate:   0.066
CYP2C19-inhibitor:   0.999 CYP2C19-substrate:   0.0
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.003
CYP2D6-inhibitor:   0.001 CYP2D6-substrate:   0.025
CYP3A4-inhibitor:   1.0 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.997
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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):  10.159 Half-life (T1/2):  0.581

ADMET: Toxicity

hERG Blockers:  0.061 hERG Blockers (10um):  0.403
Human Hepatotoxicity (H-HT):  0.722 Drug-induced Liver Injury (DILI):  0.911
AMES Toxicity:  0.818 Rat Oral Acute Toxicity:  0.343
Maximum Recommended Daily Dose:  0.736 Skin Sensitization:  1.0
Carcinogencity:  0.965 Eye Corrosion:  0.358
Eye Irritation:  0.814 Respiratory Toxicity:  0.621
Drug-induced Neurotoxicity:  0.563 Ototoxicity:  0.246
Hematotoxicity:  0.765 Drug-induced Nephrotoxicity:  0.952
Genotoxicity:  0.918 RPMI-8226 Immunitoxicity:  0.064
A549 Cytotoxicity:  0.479 Hek293 Cytotoxicity:  0.534
BCF:   2.766
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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:   5.426
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   7.122
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   7.172
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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
NPO33331 brachiaster sp. Species n.a. n.a. n.a. Thai n.a. PMID[15497961]

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
NPT83 Cell line MCF7 Homo sapiens Activity = 80.0 % PMID[17883259]
NPT139 Cell line HT-29 Homo sapiens Activity = 80.0 % PMID[15104478]
NPT165 Cell line HeLa Homo sapiens Activity = 80.0 % PMID[15104478]
NPT91 Cell line KB Homo sapiens Activity = 80.0 % PMID[17988094]
NPT88 Organism Mycobacterium tuberculosis Mycobacterium tuberculosis MIC = 4000.0 nM PMID[25615796]

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 NPC257726 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
0.8261 Intermediate Similarity NPC65513
0.7778 Intermediate Similarity NPC134077
0.7636 Intermediate Similarity NPC204054
0.65 Remote Similarity NPC112457
0.6333 Remote Similarity NPC157441
0.5818 Remote Similarity NPC605274
0.5246 Remote Similarity NPC120539
0.5231 Remote Similarity NPC94905
0.5185 Remote Similarity NPC211641
0.5082 Remote Similarity NPC602574

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC257726 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
NPD

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