Natural Product: NPC55092

Natural Product IDNPC55092
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Sumalarin A
IUPAC Name methyl (2S)-3-[[(5S,9S)-13,15-dihydroxy-5-methyl-3,11-dioxo-4-oxabicyclo[10.4.0]hexadeca-1(12),13,15-trien-9-yl]sulfanyl]-2-hydroxypropanoate
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL3087767
PubChem CID 72945489
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000147] Macrolides and analogues

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 YXJPFYMQMMDSJU-PZSREKOKSA-N
Standard InCHI InChI=1S/C20H26O8S/c1-11-4-3-5-14(29-10-17(24)20(26)27-2)9-16(23)19-12(7-18(25)28-11)6-13(21)8-15(19)22/h6,8,11,14,17,21-22,24H,3-5,7,9-10H2,1-2H3/t11-,14-,17+/m0/s1
SMILES COC(=O)[C@@H](CS[C@H]1CCC[C@H](C)OC(=O)Cc2c(C(=O)C1)c(O)cc(c2)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   426.13 Volume:   410.375
?
Van der Waals volume.
Dense:   1.038 LogP:   1.553
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.951
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.928
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The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   20.0
TPSA:   130.36
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Topological Polar Surface Area.
 H-Bond Acceptor:   8.0
H-Bond Donor:   3.0 Rings:   2.0
Heavy Atoms:   9.0

MedChem Properties

QED Drug-Likeness Score:   0.618 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.512 Fsp3:   0.55
MCE-18:   55.226
?
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:   0.393 Fluc inhibitor:   0.222
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.028
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.364
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.107 Promiscuous compounds:   0.735

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.825 MDCK Permeability:   -5.073
Pgp-inhibitor:   0.013 Pgp-substrate:   0.767
PAMPA:   0.269
?
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%):   0.001 30% Bioavailability (F30%):   0.184
50% Bioavailability (F50%):   0.932

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.227
Plasma Protein Binding (PPB):   91.243% Volume Distribution (VD):   0.064
Fu: 6.524%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   0.01
BSEP inhibitor:   0.952

ADMET: Metabolism

CYP1A2-inhibitor:   0.978 CYP1A2-substrate:   0.979
CYP2C19-inhibitor:   0.012 CYP2C19-substrate:   0.587
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.007
CYP2D6-inhibitor:   0.018 CYP2D6-substrate:   0.925
CYP3A4-inhibitor:   0.013 CYP3A4-substrate:   0.046
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.995
HLM stability:   1.0
?
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):  2.936 Half-life (T1/2):  1.714

ADMET: Toxicity

hERG Blockers:  0.016 hERG Blockers (10um):  0.215
Human Hepatotoxicity (H-HT):  0.712 Drug-induced Liver Injury (DILI):  0.981
AMES Toxicity:  0.977 Rat Oral Acute Toxicity:  0.239
Maximum Recommended Daily Dose:  0.451 Skin Sensitization:  1.0
Carcinogencity:  0.837 Eye Corrosion:  0.007
Eye Irritation:  0.726 Respiratory Toxicity:  0.169
Drug-induced Neurotoxicity:  0.443 Ototoxicity:  0.589
Hematotoxicity:  0.121 Drug-induced Nephrotoxicity:  0.993
Genotoxicity:  0.998 RPMI-8226 Immunitoxicity:  0.165
A549 Cytotoxicity:  0.532 Hek293 Cytotoxicity:  0.464
BCF:   0.579
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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:   3.192
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.806
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.984
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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
NPO33114 penicillium sumatrense ma-92 Species Aspergillaceae Eukaryota rhizosphere of the mangrove Lumnitzera racemosa n.a. n.a. PMID[24195466]

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
NPT1312 Cell line SW1990 Homo sapiens IC50 = 10000.0 nM PMID[14643329]
NPT90 Cell line DU-145 Homo sapiens IC50 = 6000.0 nM PMID[24900349]
NPT165 Cell line HeLa Homo sapiens IC50 = 6000.0 nM DrugMatrix in vitro pharmacology data
NPT1229 Cell line Huh-7 Homo sapiens IC50 = 3900.0 nM PMID[24485782]
NPT83 Cell line MCF7 Homo sapiens IC50 = 4400.0 nM PMID[20876376]
NPT397 Cell line NCI-H460 Homo sapiens IC50 = 3800.0 nM PMID[21846091]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 5500.0 nM PMID[24195466]

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 NPC55092 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
0.7667 Intermediate Similarity NPC474849
0.7667 Intermediate Similarity NPC65837
0.7667 Intermediate Similarity NPC149372
0.7 Intermediate Similarity NPC213224
0.6761 Remote Similarity NPC275837
0.6212 Remote Similarity NPC475974
0.6094 Remote Similarity NPC178467
0.6094 Remote Similarity NPC474771
0.5606 Remote Similarity NPC474655
0.5588 Remote Similarity NPC354984
0.5441 Remote Similarity NPC177307
0.5441 Remote Similarity NPC9121

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC55092 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