Natural Product: NPC278386

Natural Product IDNPC278386
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (S)-4-Hydroxy-3-(2-((1R,4As,5R,6R,8As)-6-Hydroxy-5-(Hydroxymethyl)-5,8A-Dimethyl-2-Methylene-Decahydronaphthalen-1-Yl)Ethylidene)-Dihydrofuran-2(3H)-One
IUPAC Name (3Z,4S)-3-[2-[(1R,4aS,5R,6R,8aS)-6-hydroxy-5-(hydroxymethyl)-5,8a-dimethyl-2-methylidene-3,4,4a,6,7,8-hexahydro-1H-naphthalen-1-yl]ethylidene]-4-hydroxyoxolan-2-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL466345
PubChem CID 7067324
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0000050] Lactones
        • [CHEMONTID:0001245] Gamma butyrolactones

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 BOJKULTULYSRAS-QPSYGYIJSA-N
Standard InCHI InChI=1S/C20H30O5/c1-12-4-7-16-19(2,9-8-17(23)20(16,3)11-21)14(12)6-5-13-15(22)10-25-18(13)24/h5,14-17,21-23H,1,4,6-11H2,2-3H3/b13-5-/t14-,15-,16+,17-,19+,20+/m1/s1
SMILES OC[C@]1(C)[C@H](O)CC[C@@]2([C@@H]1CCC(=C)[C@H]2C/C=C1/[C@H](O)COC1=O)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   350.21 Volume:   364.849
?
Van der Waals volume.
Dense:   0.96 LogP:   2.551
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.595
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.208
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   19.0
TPSA:   86.99
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   3.0 Rings:   3.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.411 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.705 Fsp3:   0.75
MCE-18:   57.829
?
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:   0.299 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.007
?
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:   0.46 Promiscuous compounds:   0.306

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.085 MDCK Permeability:   -4.845
Pgp-inhibitor:   0.062 Pgp-substrate:   0.022
PAMPA:   0.934
?
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):   0.004
20% Bioavailability (F20%):   0.554 30% Bioavailability (F30%):   0.518
50% Bioavailability (F50%):   0.994

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.762 MRP1:   0.49
Plasma Protein Binding (PPB):   65.275% Volume Distribution (VD):   -0.211
Fu: 34.988%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.995
OATP1B3 inhibitor:   0.994 BCRP inhibitor:   0.553
BSEP inhibitor:   0.879

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.36
CYP2C9-inhibitor:   0.003 CYP2C9-substrate:   0.004
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.059 CYP3A4-substrate:   0.092
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.707
HLM stability:   0.146
?
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):  9.561 Half-life (T1/2):  1.599

ADMET: Toxicity

hERG Blockers:  0.033 hERG Blockers (10um):  0.203
Human Hepatotoxicity (H-HT):  0.855 Drug-induced Liver Injury (DILI):  0.377
AMES Toxicity:  0.747 Rat Oral Acute Toxicity:  0.639
Maximum Recommended Daily Dose:  0.95 Skin Sensitization:  1.0
Carcinogencity:  0.988 Eye Corrosion:  0.0
Eye Irritation:  0.316 Respiratory Toxicity:  0.306
Drug-induced Neurotoxicity:  0.294 Ototoxicity:  0.792
Hematotoxicity:  0.705 Drug-induced Nephrotoxicity:  0.988
Genotoxicity:  0.952 RPMI-8226 Immunitoxicity:  0.212
A549 Cytotoxicity:  0.609 Hek293 Cytotoxicity:  0.675
BCF:   0.618
?
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:   3.486
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.248
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.39
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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
NPO3578 Andrographis paniculata Species Acanthaceae Eukaryota n.a. n.a. n.a. DOI[10.1111/ppl.12252]
NPO3578 Andrographis paniculata Species Acanthaceae Eukaryota n.a. leaf n.a. PMID[15894448]
NPO3578 Andrographis paniculata Species Acanthaceae Eukaryota n.a. root n.a. PMID[15894448]
NPO3578 Andrographis paniculata Species Acanthaceae Eukaryota aerial parts purchased in Juhuacun herbal market, Kunming, Yunnan Province, China 2002-Oct PMID[16562826]
NPO3578 Andrographis paniculata Species Acanthaceae Eukaryota n.a. n.a. n.a. PMID[18357994]
NPO3578 Andrographis paniculata Species Acanthaceae Eukaryota n.a. leaf n.a. PMID[21598983]
NPO3578 Andrographis paniculata Species Acanthaceae Eukaryota n.a. leaf n.a. PMID[22026410]
NPO3578 Andrographis paniculata Species Acanthaceae Eukaryota n.a. n.a. n.a. PMID[8377022]
NPO3578 Andrographis paniculata Species Acanthaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3578 Andrographis paniculata Species Acanthaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO3578 Andrographis paniculata Species Acanthaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO3578 Andrographis paniculata Species Acanthaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO3578 Andrographis paniculata Species Acanthaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO3578 Andrographis paniculata Species Acanthaceae Eukaryota n.a. n.a. n.a. Database[UNPD]

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
NPT116 Cell line HL-60 Homo sapiens GI50 = 6300.0 nM PMID[18357994]

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 NPC278386 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 NPC159763
1.0 High Similarity NPC124512
0.7679 Intermediate Similarity NPC72845
0.717 Intermediate Similarity NPC476949
0.7069 Intermediate Similarity NPC242848
0.7069 Intermediate Similarity NPC191521
0.6964 Remote Similarity NPC79027
0.6935 Remote Similarity NPC73911
0.6842 Remote Similarity NPC139692
0.6552 Remote Similarity NPC131813
0.6471 Remote Similarity NPC264153
0.6271 Remote Similarity NPC77001
0.6271 Remote Similarity NPC478375
0.6271 Remote Similarity NPC253618
0.5902 Remote Similarity NPC152778
0.5902 Remote Similarity NPC205034
0.5893 Remote Similarity NPC470428
0.5862 Remote Similarity NPC488426
0.5833 Remote Similarity NPC476602
0.55 Remote Similarity NPC608380
0.5484 Remote Similarity NPC104560
0.5469 Remote Similarity NPC234993
0.5469 Remote Similarity NPC134072
0.5333 Remote Similarity NPC474433
0.5312 Remote Similarity NPC474440
0.5231 Remote Similarity NPC16967
0.5224 Remote Similarity NPC325594

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC278386 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
1.0 High Similarity NPD4225 Phase 3

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