Natural Product: NPC149372

Natural Product IDNPC149372
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 11Alpha-Methoxycurvularin
IUPAC Name (5S,9S)-13,15-dihydroxy-9-methoxy-5-methyl-4-oxabicyclo[10.4.0]hexadeca-1(12),13,15-triene-3,11-dione
Synonyms 11Alpha-Methoxycurvularin
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1643634
PubChem CID 14829838
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 LBVPDFGFLMFDPI-GWCFXTLKSA-N
Standard InCHI InChI=1S/C17H22O6/c1-10-4-3-5-13(22-2)9-15(20)17-11(7-16(21)23-10)6-12(18)8-14(17)19/h6,8,10,13,18-19H,3-5,7,9H2,1-2H3/t10-,13-/m0/s1
SMILES CO[C@H]1CCC[C@H](C)OC(=O)Cc2c(C(=O)C1)c(O)cc(c2)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   322.14 Volume:   325.034
?
Van der Waals volume.
Dense:   0.991 LogP:   1.414
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.849
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.919
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The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   19.0
TPSA:   93.06
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Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   2.0 Rings:   2.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.771 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.997 Fsp3:   0.529
MCE-18:   49.538
?
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:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.094 Fluc inhibitor:   0.254
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.106
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.306
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.265 Promiscuous compounds:   0.431

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.929 MDCK Permeability:   -4.772
Pgp-inhibitor:   0.175 Pgp-substrate:   0.198
PAMPA:   0.265
?
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%):   0.004 30% Bioavailability (F30%):   0.249
50% Bioavailability (F50%):   0.842

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.002 MRP1:   0.433
Plasma Protein Binding (PPB):   89.111% Volume Distribution (VD):   -0.159
Fu: 10.276%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.991
OATP1B3 inhibitor:   0.998 BCRP inhibitor:   0.613
BSEP inhibitor:   0.223

ADMET: Metabolism

CYP1A2-inhibitor:   0.433 CYP1A2-substrate:   0.037
CYP2C19-inhibitor:   0.025 CYP2C19-substrate:   0.06
CYP2C9-inhibitor:   0.014 CYP2C9-substrate:   0.002
CYP2D6-inhibitor:   0.001 CYP2D6-substrate:   0.86
CYP3A4-inhibitor:   0.004 CYP3A4-substrate:   0.082
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.259
HLM stability:   0.869
?
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):  3.253 Half-life (T1/2):  1.614

ADMET: Toxicity

hERG Blockers:  0.032 hERG Blockers (10um):  0.22
Human Hepatotoxicity (H-HT):  0.708 Drug-induced Liver Injury (DILI):  0.684
AMES Toxicity:  0.918 Rat Oral Acute Toxicity:  0.16
Maximum Recommended Daily Dose:  0.818 Skin Sensitization:  0.999
Carcinogencity:  0.87 Eye Corrosion:  0.077
Eye Irritation:  0.952 Respiratory Toxicity:  0.261
Drug-induced Neurotoxicity:  0.726 Ototoxicity:  0.46
Hematotoxicity:  0.187 Drug-induced Nephrotoxicity:  0.971
Genotoxicity:  0.592 RPMI-8226 Immunitoxicity:  0.172
A549 Cytotoxicity:  0.597 Hek293 Cytotoxicity:  0.417
BCF:   0.423
?
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:   2.891
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.189
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.453
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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
NPO30770 Penicillium sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[10479323]
NPO30770 Penicillium sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[12350167]
NPO30770 Penicillium sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[14640527]
NPO30770 Penicillium sp. Species Aspergillaceae Eukaryota Axinella verrucosa Mediterranean n.a. PMID[14738391]
NPO30770 Penicillium sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[15043411]
NPO30770 Penicillium sp. Species Aspergillaceae Eukaryota n.a. Sussex Inlet, New South Wales, Australia n.a. PMID[15104517]
NPO30770 Penicillium sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[15332862]
NPO30770 Penicillium sp. Species Aspergillaceae Eukaryota n.a. Berkeley Pit lake n.a. PMID[17970594]
NPO30770 Penicillium sp. Species Aspergillaceae Eukaryota n.a. New Zealand n.a. PMID[19323568]
NPO30770 Penicillium sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[19326880]
NPO30770 Penicillium sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[20452770]
NPO30770 Penicillium sp. Species Aspergillaceae Eukaryota n.a. North Sea n.a. PMID[21126094]
NPO30770 Penicillium sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[21126094]
NPO30770 Penicillium sp. Species Aspergillaceae Eukaryota n.a. Limonium tubiflorum n.a. PMID[21146414]
NPO30770 Penicillium sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[21916432]
NPO30770 Penicillium sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[22148349]
NPO30770 Penicillium sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[22458669]
NPO30770 Penicillium sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[23360521]
NPO30770 Penicillium sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[23477451]
NPO30770 Penicillium sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[23603293]
NPO30770 Penicillium sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[23972215]
NPO30770 Penicillium sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[24033077]
NPO30770 Penicillium sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[24437979]
NPO30770 Penicillium sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[31433188]
NPO30770 Penicillium sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[9392888]
NPO30770 Penicillium sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. Database[Article]
NPO30770 Penicillium sp. Species Aspergillaceae 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
NPT111 Cell line K562 Homo sapiens IC50 = 41100.0 nM PMID[22770608]
NPT15 Cell line Jurkat Homo sapiens IC50 = 2300.0 nM PMID[26295746]
NPT466 Cell line U-937 Homo sapiens IC50 = 4600.0 nM PMID[20687534]
NPT471 Organism Trypanosoma brucei brucei Trypanosoma brucei brucei MIC = 9680.0 nM PMID[19761234]
NPT2 Others Unspecified n.a. IC50 = 10100.0 nM PMID[16124770]

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 NPC149372 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 NPC474849
1.0 High Similarity NPC65837
0.7667 Intermediate Similarity NPC55092
0.7222 Intermediate Similarity NPC178467
0.7222 Intermediate Similarity NPC474771
0.7031 Intermediate Similarity NPC275837
0.7031 Intermediate Similarity NPC213224
0.6724 Remote Similarity NPC475974
0.6552 Remote Similarity NPC354984
0.6379 Remote Similarity NPC177307
0.6379 Remote Similarity NPC9121
0.6034 Remote Similarity NPC474655
0.5593 Remote Similarity NPC605699
0.5577 Remote Similarity NPC164870

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC149372 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