Natural Product: NPC9121

Natural Product IDNPC9121
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Dehydrocurvularin
IUPAC Name (5S,9E)-13,15-dihydroxy-5-methyl-4-oxabicyclo[10.4.0]hexadeca-1(12),9,13,15-tetraene-3,11-dione
Synonyms Dehydrocurvularin; Trans-Dehydrocurvularin
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL520014
PubChem CID 6438143
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 AVIRMQMUBGNCKS-RWCYGVJQSA-N
Standard InCHI InChI=1S/C16H18O5/c1-10-5-3-2-4-6-13(18)16-11(8-15(20)21-10)7-12(17)9-14(16)19/h4,6-7,9-10,17,19H,2-3,5,8H2,1H3/b6-4+/t10-/m0/s1
SMILES C[C@H]1CCC/C=C/C(=O)c2c(cc(cc2O)O)CC(=O)O1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   290.12 Volume:   296.312
?
Van der Waals volume.
Dense:   0.979 LogP:   1.944
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.223
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.647
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   0.0 Rigid Bonds:   19.0
TPSA:   83.83
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   2.0 Rings:   2.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.717 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.792 Fsp3:   0.375
MCE-18:   44.909
?
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:   0.221 Fluc inhibitor:   0.808
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.285
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.464
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.398 Promiscuous compounds:   0.407

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.194 MDCK Permeability:   -4.794
Pgp-inhibitor:   0.345 Pgp-substrate:   0.02
PAMPA:   0.006
?
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%):   0.051 30% Bioavailability (F30%):   0.751
50% Bioavailability (F50%):   0.724

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.001 MRP1:   0.436
Plasma Protein Binding (PPB):   97.154% Volume Distribution (VD):   -0.181
Fu: 2.715%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.994
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   0.259
BSEP inhibitor:   0.978

ADMET: Metabolism

CYP1A2-inhibitor:   0.985 CYP1A2-substrate:   0.865
CYP2C19-inhibitor:   0.001 CYP2C19-substrate:   0.665
CYP2C9-inhibitor:   0.28 CYP2C9-substrate:   0.998
CYP2D6-inhibitor:   0.051 CYP2D6-substrate:   1.0
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.996
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.963
?
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):  1.357 Half-life (T1/2):  1.487

ADMET: Toxicity

hERG Blockers:  0.059 hERG Blockers (10um):  0.144
Human Hepatotoxicity (H-HT):  0.866 Drug-induced Liver Injury (DILI):  0.95
AMES Toxicity:  0.765 Rat Oral Acute Toxicity:  0.028
Maximum Recommended Daily Dose:  0.87 Skin Sensitization:  0.999
Carcinogencity:  0.205 Eye Corrosion:  0.031
Eye Irritation:  0.996 Respiratory Toxicity:  0.587
Drug-induced Neurotoxicity:  0.428 Ototoxicity:  0.183
Hematotoxicity:  0.087 Drug-induced Nephrotoxicity:  0.776
Genotoxicity:  0.905 RPMI-8226 Immunitoxicity:  0.335
A549 Cytotoxicity:  0.781 Hek293 Cytotoxicity:  0.791
BCF:   0.947
?
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:   3.675
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.797
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.321
?
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]
NPO31572 Aspergillus sp. Species Aspergillaceae Eukaryota rhizosphere Sonoran desert n.a. PMID[15620238]
NPO31572 Aspergillus sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[17542490]
NPO31572 Aspergillus sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[17564467]
NPO30770 Penicillium sp. Species Aspergillaceae Eukaryota n.a. Berkeley Pit lake n.a. PMID[17970594]
NPO31572 Aspergillus sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[19053517]
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. n.a. n.a. PMID[21126094]
NPO30770 Penicillium sp. Species Aspergillaceae Eukaryota n.a. North Sea n.a. PMID[21126094]
NPO30770 Penicillium sp. Species Aspergillaceae Eukaryota n.a. Limonium tubiflorum n.a. PMID[21146414]
NPO31572 Aspergillus sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[21366228]
NPO31572 Aspergillus sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[21718031]
NPO31572 Aspergillus sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[21854017]
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]
NPO31572 Aspergillus sp. Species Aspergillaceae Eukaryota healthy leaf of Ginkgo biloba campus of Nanjing University, Nanjing, China 2008-OCT PMID[22196792]
NPO31572 Aspergillus sp. Species Aspergillaceae Eukaryota isolated from the sponge Xestospongia testudinaria n.a. n.a. PMID[22225637]
NPO31572 Aspergillus sp. Species Aspergillaceae Eukaryota Isolated from a sandy-loam soil sample 50 m inland from Waikiki Beach, Honolulu, Hawaii 2010-JUL PMID[22400916]
NPO30770 Penicillium sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[22458669]
NPO31572 Aspergillus sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[22703109]
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]
NPO31572 Aspergillus sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[23527875]
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]
NPO31572 Aspergillus sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[24050204]
NPO33114 penicillium sumatrense ma-92 Species Aspergillaceae Eukaryota rhizosphere of the mangrove Lumnitzera racemosa n.a. n.a. PMID[24195466]
NPO30770 Penicillium sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[24437979]
NPO31572 Aspergillus sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[25001296]
NPO31572 Aspergillus sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[25581396]
NPO31572 Aspergillus sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[26273902]
NPO41084 Coniochaeta sp. FL1031 Strain Coniochaetaceae Eukaryota n.a. n.a. n.a. PMID[26812276]
NPO41085 Coniochaeta sp. FL1375 Strain Coniochaetaceae Eukaryota n.a. n.a. n.a. PMID[26812276]
NPO40432 Alternaria sp. AST0039 Strain Pleosporaceae Eukaryota n.a. n.a. n.a. PMID[28139929]
NPO31572 Aspergillus sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[31012585]
NPO30770 Penicillium sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[31433188]
NPO31572 Aspergillus sp. Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[33305943]
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]
NPO40432 Alternaria sp. AST0039 Strain Pleosporaceae 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
NPT1583 Individual protein Heat shock factor protein 1 Homo sapiens IC50 = 15300.0 nM PMID[32652407]
NPT29345 Single protein Gem-associated protein 4 Homo sapiens IC50 = 15300.0 nM PMID[33873056]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT397 Cell line NCI-H460 Homo sapiens IC50 = 1100.0 nM Open TG-GATES in vivo data: Biochemistry
NPT83 Cell line MCF7 Homo sapiens IC50 = 1300.0 nM PMID[16420055]
NPT395 Cell line SF-268 Homo sapiens IC50 = 2500.0 nM PMID[24216090]
NPT783 Cell line MIA PaCa-2 Homo sapiens IC50 = 1900.0 nM PMID[25226228]
NPT111 Cell line K562 Homo sapiens IC50 = 37000.0 nM Open TG-GATES in vivo data: Pathology
NPT15 Cell line Jurkat Homo sapiens IC50 = 5500.0 nM Open TG-GATES in vivo data: Hematology
NPT466 Cell line U-937 Homo sapiens IC50 = 2500.0 nM PMID[20022253]
NPT397 Cell line NCI-H460 Homo sapiens IC50 = 5000.0 nM PMID[850238]
NPT1312 Cell line SW1990 Homo sapiens IC50 = 10000.0 nM PMID[10096854]
NPT90 Cell line DU-145 Homo sapiens IC50 = 6000.0 nM PMID[19654408]
NPT165 Cell line HeLa Homo sapiens IC50 = 6000.0 nM PMID[19658408]
NPT1229 Cell line Huh-7 Homo sapiens IC50 = 5000.0 nM PubChem BioAssay data set
NPT83 Cell line MCF7 Homo sapiens IC50 = 4000.0 nM PMID[14738392]
NPT82 Cell line MDA-MB-231 Homo sapiens IC50 > 5000.0 nM PMID[28139929]
NPT83 Cell line MCF7 Homo sapiens IC50 = 3980.0 nM PMID[28139929]
NPT395 Cell line SF-268 Homo sapiens IC50 = 4730.0 nM PMID[28139929]
NPT397 Cell line NCI-H460 Homo sapiens IC50 = 3570.0 nM PMID[28139929]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 6000.0 nM PMID[24195466]
NPT471 Organism Trypanosoma brucei brucei Trypanosoma brucei brucei MIC > 100000.0 nM PMID[17261619]
NPT2 Others Unspecified n.a. IC50 = 5600.0 nM PMID[17958396]
NPT2 Others Unspecified n.a. IC50 = 1700.0 nM PMID[23350742]
NPT2 Others Unspecified n.a. IC50 = 4400.0 nM PMID[17360571]
NPT23103 Cell line PC-3M Homo sapiens IC50 = 4510.0 nM PMID[28139929]

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 NPC9121 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 NPC177307
0.7069 Intermediate Similarity NPC489318
0.7037 Intermediate Similarity NPC178467
0.7037 Intermediate Similarity NPC474771
0.6379 Remote Similarity NPC474849
0.6379 Remote Similarity NPC65837
0.6379 Remote Similarity NPC149372
0.6379 Remote Similarity NPC354984
0.6271 Remote Similarity NPC475974
0.5806 Remote Similarity NPC489317
0.5593 Remote Similarity NPC474655
0.5441 Remote Similarity NPC55092
0.5385 Remote Similarity NPC164870
0.5238 Remote Similarity NPC472403
0.5211 Remote Similarity NPC275837
0.5211 Remote Similarity NPC213224
0.5167 Remote Similarity NPC605699
0.5079 Remote Similarity NPC609527
0.5079 Remote Similarity NPC611086

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC9121 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