Natural Product: NPC474098

Natural Product IDNPC474098
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Epi-Sarcotin F
IUPAC Name (2R)-3-hydroxy-2-[(2Z,6S,7E,9E)-13-(2-methoxy-5-oxo-2H-furan-4-yl)-2,6,10-trimethyltrideca-2,7,9-trienyl]-4-methyl-2H-furan-5-one
Synonyms Epi-Sarcotin F
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL461401
PubChem CID 54710663
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0000259] Prenol lipids
        • [CHEMONTID:0001283] Terpene lactones
          • [CHEMONTID:0001538] Diterpene lactones

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 RUXYPSKOCAEMCR-ZQBGMYTGSA-N
Standard InCHI InChI=1S/C26H36O6/c1-17(11-7-13-19(3)15-22-24(27)20(4)25(28)31-22)9-6-10-18(2)12-8-14-21-16-23(30-5)32-26(21)29/h6,9-10,13,16-17,22-23,27H,7-8,11-12,14-15H2,1-5H3/b9-6+,18-10+,19-13-/t17-,22-,23?/m1/s1
SMILES COC1OC(=O)C(=C1)CCC/C(=C/C=C/[C@H](CC/C=C(C[C@H]1OC(=O)C(=C1O)C)/C)C)/C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   444.25 Volume:   475.425
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Van der Waals volume.
Dense:   0.934 LogP:   4.452
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.815
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.684
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The logarithm of aqueous solubility value.
Rotatable Bonds:   12.0 Rigid Bonds:   15.0
TPSA:   82.06
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Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   1.0 Rings:   2.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.239 GASA:   1.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.706 Fsp3:   0.538
MCE-18:   33.6
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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:   Rejected GSK Rule:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.798 Fluc inhibitor:   0.086
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.029
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.536
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.618 Promiscuous compounds:   0.043

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.103 MDCK Permeability:   -4.911
Pgp-inhibitor:   0.037 Pgp-substrate:   0.37
PAMPA:   0.729
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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%):   0.478 30% Bioavailability (F30%):   0.928
50% Bioavailability (F50%):   0.94

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.002 MRP1:   0.982
Plasma Protein Binding (PPB):   96.556% Volume Distribution (VD):   -0.43
Fu: 3.166%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.84
OATP1B3 inhibitor:   0.538 BCRP inhibitor:   0.018
BSEP inhibitor:   0.999

ADMET: Metabolism

CYP1A2-inhibitor:   0.313 CYP1A2-substrate:   0.919
CYP2C19-inhibitor:   0.04 CYP2C19-substrate:   0.719
CYP2C9-inhibitor:   0.428 CYP2C9-substrate:   0.004
CYP2D6-inhibitor:   0.007 CYP2D6-substrate:   0.012
CYP3A4-inhibitor:   0.19 CYP3A4-substrate:   0.227
CYP2B6-substrate:   0.061 CYP2C8-inhibitor:   0.975
HLM stability:   0.627
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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):  6.142 Half-life (T1/2):  0.573

ADMET: Toxicity

hERG Blockers:  0.035 hERG Blockers (10um):  0.155
Human Hepatotoxicity (H-HT):  0.779 Drug-induced Liver Injury (DILI):  0.764
AMES Toxicity:  0.489 Rat Oral Acute Toxicity:  0.422
Maximum Recommended Daily Dose:  0.598 Skin Sensitization:  0.999
Carcinogencity:  0.332 Eye Corrosion:  0.006
Eye Irritation:  0.461 Respiratory Toxicity:  0.079
Drug-induced Neurotoxicity:  0.321 Ototoxicity:  0.612
Hematotoxicity:  0.454 Drug-induced Nephrotoxicity:  0.979
Genotoxicity:  0.611 RPMI-8226 Immunitoxicity:  0.113
A549 Cytotoxicity:  0.04 Hek293 Cytotoxicity:  0.078
BCF:   1.694
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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:   4.986
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.5
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   6.024
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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
NPO33166 Sarcotragus Genus Irciniidae Eukaryota n.a. n.a. n.a. PMID[14640517]

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
NPT81 Cell line A549 Homo sapiens ED50 > 30.0 ug ml-1 PMID[25338277]
NPT146 Cell line SK-OV-3 Homo sapiens ED50 > 30.0 ug ml-1 PMID[26241103]
NPT147 Cell line SK-MEL-2 Homo sapiens ED50 = 10.9 ug ml-1 PMID[26241103]
NPT574 Cell line XF498 Homo sapiens ED50 > 30.0 ug ml-1 DOI[10.6019/CHEMBL1201861]
NPT148 Cell line HCT-15 Homo sapiens ED50 = 33.0 ug ml-1 PMID[25299458]

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 NPC474098 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 NPC475995
0.6418 Remote Similarity NPC52820
0.6269 Remote Similarity NPC68001
0.6269 Remote Similarity NPC199831
0.6087 Remote Similarity NPC474828
0.6087 Remote Similarity NPC474827
0.5753 Remote Similarity NPC474099
0.5676 Remote Similarity NPC474244
0.5479 Remote Similarity NPC329922
0.5479 Remote Similarity NPC81912
0.5479 Remote Similarity NPC329694
0.5479 Remote Similarity NPC474260
0.5479 Remote Similarity NPC611156
0.525 Remote Similarity NPC165726
0.525 Remote Similarity NPC213969

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC474098 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