Natural Product: NPC271441

Natural Product IDNPC271441
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 JJTXQCMHUFFVOF-RIYZIHGNSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 5363699
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0000259] Prenol lipids
        • [CHEMONTID:0001550] Sesquiterpenoids

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 JJTXQCMHUFFVOF-RIYZIHGNSA-N
Standard InCHI InChI=1S/C18H30O/c1-14(8-6-10-16(3)19)11-12-17-15(2)9-7-13-18(17,4)5/h8H,6-7,9-13H2,1-5H3/b14-8+
SMILES C/C(=CCCC(=O)C)/CCC1=C(C)CCCC1(C)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   262.23 Volume:   312.209
?
Van der Waals volume.
Dense:   0.84 LogP:   4.785
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.625
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.403
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   8.0
TPSA:   17.07
?
Topological Polar Surface Area.
 H-Bond Acceptor:   1.0
H-Bond Donor:   0.0 Rings:   1.0
Heavy Atoms:   1.0

MedChem Properties

QED Drug-Likeness Score:   0.569 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.901 Fsp3:   0.722
MCE-18:   12.581
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Accepted GSK Rule:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.109 Fluc inhibitor:   0.034
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.002
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.002
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.994 Promiscuous compounds:   0.085

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.527 MDCK Permeability:   -4.741
Pgp-inhibitor:   0.88 Pgp-substrate:   0.004
PAMPA:   0.001
?
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%):   0.0 30% Bioavailability (F30%):   0.0
50% Bioavailability (F50%):   0.04

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.08 MRP1:   0.993
Plasma Protein Binding (PPB):   96.733% Volume Distribution (VD):   0.437
Fu: 3.536%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.5
OATP1B3 inhibitor:   0.417 BCRP inhibitor:   0.002
BSEP inhibitor:   0.997

ADMET: Metabolism

CYP1A2-inhibitor:   0.618 CYP1A2-substrate:   0.023
CYP2C19-inhibitor:   0.995 CYP2C19-substrate:   0.006
CYP2C9-inhibitor:   0.681 CYP2C9-substrate:   0.361
CYP2D6-inhibitor:   0.546 CYP2D6-substrate:   0.039
CYP3A4-inhibitor:   0.743 CYP3A4-substrate:   0.914
CYP2B6-substrate:   0.32 CYP2C8-inhibitor:   0.724
HLM stability:   0.833
?
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):  8.017 Half-life (T1/2):  0.359

ADMET: Toxicity

hERG Blockers:  0.053 hERG Blockers (10um):  0.397
Human Hepatotoxicity (H-HT):  0.657 Drug-induced Liver Injury (DILI):  0.227
AMES Toxicity:  0.127 Rat Oral Acute Toxicity:  0.202
Maximum Recommended Daily Dose:  0.567 Skin Sensitization:  0.852
Carcinogencity:  0.413 Eye Corrosion:  0.398
Eye Irritation:  0.949 Respiratory Toxicity:  0.814
Drug-induced Neurotoxicity:  0.581 Ototoxicity:  0.471
Hematotoxicity:  0.549 Drug-induced Nephrotoxicity:  0.577
Genotoxicity:  0.075 RPMI-8226 Immunitoxicity:  0.051
A549 Cytotoxicity:  0.024 Hek293 Cytotoxicity:  0.129
BCF:   2.253
?
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:   4.778
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.776
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.635
?
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
NPO40711 Diacarnus cf. spinopoculum Strain Podospongiidae Eukaryota n.a. n.a. n.a. PMID[9514009]
NPO40711 Diacarnus cf. spinopoculum Strain Podospongiidae 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
NPT404 Cell line CCRF-CEM Homo sapiens GI50 = 2940.0 nM PMID[9514009]
NPT116 Cell line HL-60 Homo sapiens GI50 = 2880.0 nM PMID[9514009]
NPT112 Cell line MOLT-4 Homo sapiens GI50 = 2080.0 nM PMID[9514009]
NPT385 Cell line SR Homo sapiens GI50 = 4940.0 nM PMID[9514009]
NPT81 Cell line A549 Homo sapiens GI50 > 15000.0 nM PMID[9514009]
NPT394 Cell line EKVX Homo sapiens GI50 > 15000.0 nM PMID[9514009]
NPT379 Cell line HOP-62 Homo sapiens GI50 > 15000.0 nM PMID[9514009]
NPT372 Cell line HOP-92 Homo sapiens GI50 > 15000.0 nM PMID[9514009]
NPT405 Cell line NCI-H226 Homo sapiens GI50 > 15000.0 nM PMID[9514009]
NPT370 Cell line NCI-H23 Homo sapiens GI50 > 15000.0 nM PMID[9514009]
NPT388 Cell line NCI-H322M Homo sapiens GI50 > 15000.0 nM PMID[9514009]
NPT397 Cell line NCI-H460 Homo sapiens GI50 > 15000.0 nM PMID[9514009]
NPT455 Cell line NCI-H522 Homo sapiens GI50 > 15000.0 nM PMID[9514009]
NPT407 Cell line COLO 205 Homo sapiens GI50 > 15000.0 nM PMID[9514009]
NPT391 Cell line HCC 2998 Homo sapiens GI50 > 15000.0 nM PMID[9514009]
NPT393 Cell line HCT-116 Homo sapiens GI50 > 15000.0 nM PMID[9514009]
NPT148 Cell line HCT-15 Homo sapiens GI50 > 15000.0 nM PMID[9514009]
NPT139 Cell line HT-29 Homo sapiens GI50 > 15000.0 nM PMID[9514009]
NPT386 Cell line KM12 Homo sapiens GI50 = 8610.0 nM PMID[9514009]
NPT323 Cell line SW-620 Homo sapiens GI50 = 6340.0 nM PMID[9514009]
NPT399 Cell line SF-295 Homo sapiens GI50 > 15000.0 nM PMID[9514009]
NPT374 Cell line SF-539 Homo sapiens GI50 > 15000.0 nM PMID[9514009]
NPT383 Cell line SNB-19 Homo sapiens GI50 < 1.5 nM PMID[9514009]
NPT392 Cell line SNB-75 Homo sapiens GI50 = 5150.0 nM PMID[9514009]
NPT380 Cell line U-251 Homo sapiens GI50 > 15000.0 nM PMID[9514009]
NPT375 Cell line Malme-3M Homo sapiens GI50 > 15000.0 nM PMID[9514009]
NPT387 Cell line M14 Homo sapiens GI50 < 1.5 nM PMID[9514009]
NPT147 Cell line SK-MEL-2 Homo sapiens GI50 > 15000.0 nM PMID[9514009]
NPT170 Cell line SK-MEL-28 Homo sapiens GI50 > 15000.0 nM PMID[9514009]
NPT373 Cell line SK-MEL-5 Homo sapiens GI50 > 15000.0 nM PMID[9514009]
NPT403 Cell line UACC-257 Homo sapiens GI50 > 15000.0 nM PMID[9514009]
NPT398 Cell line UACC-62 Homo sapiens GI50 > 15000.0 nM PMID[9514009]
NPT458 Cell line IGROV-1 Homo sapiens GI50 = 9530.0 nM PMID[9514009]
NPT377 Cell line OVCAR-3 Homo sapiens GI50 > 15000.0 nM PMID[9514009]
NPT456 Cell line OVCAR-4 Homo sapiens GI50 > 15000.0 nM PMID[9514009]
NPT382 Cell line OVCAR-5 Homo sapiens GI50 > 15000.0 nM PMID[9514009]
NPT381 Cell line OVCAR-8 Homo sapiens GI50 > 15000.0 nM PMID[9514009]
NPT146 Cell line SK-OV-3 Homo sapiens GI50 > 15000.0 nM PMID[9514009]
NPT401 Cell line 786-0 Homo sapiens GI50 > 15000.0 nM PMID[9514009]
NPT376 Cell line A498 Homo sapiens GI50 > 15000.0 nM PMID[9514009]
NPT369 Cell line ACHN Homo sapiens GI50 > 15000.0 nM PMID[9514009]
NPT308 Cell line CAKI-1 Homo sapiens GI50 > 15000.0 nM PMID[9514009]
NPT406 Cell line RXF 393 Homo sapiens GI50 > 15000.0 nM PMID[9514009]
NPT368 Cell line SN12C Homo sapiens GI50 = 9480.0 nM PMID[9514009]
NPT371 Cell line UO-31 Homo sapiens GI50 > 15000.0 nM PMID[9514009]
NPT90 Cell line DU-145 Homo sapiens GI50 > 15000.0 nM PMID[9514009]
NPT83 Cell line MCF7 Homo sapiens GI50 > 15000.0 nM PMID[9514009]
NPT82 Cell line MDA-MB-231 Homo sapiens GI50 > 15000.0 nM PMID[9514009]
NPT400 Cell line MDA-MB-435 Homo sapiens GI50 > 15000.0 nM PMID[9514009]
NPT367 Cell line MDA-N Homo sapiens GI50 > 15000.0 nM PMID[9514009]
NPT457 Cell line BT-549 Homo sapiens GI50 > 15000.0 nM PMID[9514009]
NPT396 Cell line T47D Homo sapiens GI50 > 15000.0 nM PMID[9514009]
NPT137 Cell line L1210 Mus musculus Activity = 60.0 Zone units PMID[9514009]
NPT168 Cell line P388 Mus musculus Activity = 60.0 Zone units PMID[9514009]
NPT6285 Cell line PO3 Homo sapiens Activity = 40.0 Zone units PMID[9514009]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. GI50 > 15000.0 nM PMID[9514009]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. GI50 = 1860.0 nM PMID[9514009]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Activity = 0.0 Zone units PMID[9514009]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Activity = 30.0 Zone units PMID[9514009]

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 NPC271441 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
0.625 Remote Similarity NPC116906
0.6136 Remote Similarity NPC473756
0.5682 Remote Similarity NPC257618
0.5476 Remote Similarity NPC96962
0.5294 Remote Similarity NPC185839
0.5294 Remote Similarity NPC180840
0.5208 Remote Similarity NPC476489
0.5111 Remote Similarity NPC475251
0.5102 Remote Similarity NPC476490

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC271441 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
0.5294 Remote Similarity NPD5783 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