Natural Product: NPC604422

Natural Product IDNPC604422
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 MEDOAKSPIIOKFU-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL345778
PubChem CID n.a.
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]

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 MEDOAKSPIIOKFU-UHFFFAOYSA-N
Standard InCHI InChI=1S/C17H14O5/c1-20-14-6-3-10(7-17(14)21-2)15-9-13(19)12-5-4-11(18)8-16(12)22-15/h3-9,18H,1-2H3
SMILES COc1ccc(-c2cc(=O)c3ccc(O)cc3o2)cc1OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   298.08 Volume:   299.778
?
Van der Waals volume.
Dense:   0.994 LogP:   2.417
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.603
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.366
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   18.0
TPSA:   68.9
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   1.0 Rings:   3.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.804 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.02 Fsp3:   0.118
MCE-18:   17.0
?
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:   0.279 Fluc inhibitor:   0.994
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.99
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.757
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.469 Promiscuous compounds:   0.439

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.803 MDCK Permeability:   -4.685
Pgp-inhibitor:   0.342 Pgp-substrate:   0.635
PAMPA:   0.079
?
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):   0.081
20% Bioavailability (F20%):   0.42 30% Bioavailability (F30%):   0.706
50% Bioavailability (F50%):   0.972

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.005 MRP1:   0.732
Plasma Protein Binding (PPB):   97.202% Volume Distribution (VD):   -0.195
Fu: 2.729%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.883
OATP1B3 inhibitor:   0.996 BCRP inhibitor:   0.992
BSEP inhibitor:   0.987

ADMET: Metabolism

CYP1A2-inhibitor:   0.662 CYP1A2-substrate:   0.537
CYP2C19-inhibitor:   0.729 CYP2C19-substrate:   0.39
CYP2C9-inhibitor:   0.925 CYP2C9-substrate:   0.211
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.996
CYP3A4-inhibitor:   0.17 CYP3A4-substrate:   0.532
CYP2B6-substrate:   0.001 CYP2C8-inhibitor:   1.0
HLM stability:   0.742
?
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):  5.722 Half-life (T1/2):  1.798

ADMET: Toxicity

hERG Blockers:  0.114 hERG Blockers (10um):  0.439
Human Hepatotoxicity (H-HT):  0.407 Drug-induced Liver Injury (DILI):  0.702
AMES Toxicity:  0.599 Rat Oral Acute Toxicity:  0.403
Maximum Recommended Daily Dose:  0.752 Skin Sensitization:  0.397
Carcinogencity:  0.83 Eye Corrosion:  0.73
Eye Irritation:  0.994 Respiratory Toxicity:  0.743
Drug-induced Neurotoxicity:  0.241 Ototoxicity:  0.08
Hematotoxicity:  0.194 Drug-induced Nephrotoxicity:  0.084
Genotoxicity:  0.956 RPMI-8226 Immunitoxicity:  0.064
A549 Cytotoxicity:  0.117 Hek293 Cytotoxicity:  0.641
BCF:   0.957
?
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:   3.755
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.509
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.169
?
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
NPO60333 Launaea asplenifolia Genus Asteraceae 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
NPT3117 Individual protein Glutaminyl-peptide cyclotransferase Homo sapiens Inhibition = 68.3 % PMID[27061673]
NPT2749 Individual protein Acetylcholinesterase Rattus norvegicus IC50 = 37.3 nM PMID[29089261]
NPT3213 Individual protein MAP kinase signal-integrating kinase 2 Homo sapiens Inhibition > 50.0 % PMID[33026809]
NPT1315 Individual protein Adenosine A1 receptor Rattus norvegicus pKi(uM) = -1.27 n.a. PMID[9438021]
NPT1315 Individual protein Adenosine A1 receptor Rattus norvegicus Ki = 18800.0 nM PMID[8576921]
NPT218 Individual protein Adenosine A3 receptor Homo sapiens pKi(uM) n.a. n.a. n.a. PMID[9438021]
NPT1316 Individual protein Adenosine A2a receptor Rattus norvegicus Ki = 35400.0 nM PMID[8576921]
NPT1316 Individual protein Adenosine A2a receptor Rattus norvegicus pKi(uM) = -1.54 n.a. PMID[9438021]
NPT218 Individual protein Adenosine A3 receptor Homo sapiens Displacement = 32.0 % PMID[8576921]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT147 Cell line SK-MEL-2 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT137 Cell line L1210 Mus musculus Activity n.a. n.a. n.a. PMID[469554]
NPT405 Cell line NCI-H226 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT369 Cell line ACHN Homo sapiens GI50 n.a. 48865.24 nM PubChem BioAssay data set
NPT139 Cell line HT-29 Homo sapiens GI50 n.a. 41783.04 nM PubChem BioAssay data set
NPT400 Cell line MDA-MB-435 Homo sapiens GI50 n.a. 45498.81 nM PubChem BioAssay data set
NPT306 Cell line PC-3 Homo sapiens GI50 n.a. 32284.94 nM PubChem BioAssay data set
NPT377 Cell line OVCAR-3 Homo sapiens GI50 n.a. 57279.6 nM PubChem BioAssay data set
NPT373 Cell line SK-MEL-5 Homo sapiens GI50 n.a. 15205.48 nM PubChem BioAssay data set
NPT83 Cell line MCF7 Homo sapiens GI50 n.a. 25822.6 nM PubChem BioAssay data set
NPT392 Cell line SNB-75 Homo sapiens GI50 n.a. 10185.91 nM PubChem BioAssay data set
NPT81 Cell line A549 Homo sapiens GI50 n.a. 38547.84 nM PubChem BioAssay data set
NPT368 Cell line SN12C Homo sapiens GI50 n.a. 41304.75 nM PubChem BioAssay data set
NPT402 Cell line Hs-578T Homo sapiens GI50 n.a. 32734.07 nM PubChem BioAssay data set
NPT390 Cell line LOX IMVI Homo sapiens GI50 n.a. 33496.54 nM PubChem BioAssay data set
NPT372 Cell line HOP-92 Homo sapiens GI50 n.a. 56623.93 nM PubChem BioAssay data set
NPT378 Cell line NCI/ADR-RES Homo sapiens GI50 n.a. 34914.03 nM PubChem BioAssay data set
NPT399 Cell line SF-295 Homo sapiens GI50 n.a. 31260.79 nM PubChem BioAssay data set
NPT82 Cell line MDA-MB-231 Homo sapiens GI50 n.a. 77446.18 nM PubChem BioAssay data set
NPT388 Cell line NCI-H322M Homo sapiens GI50 n.a. 26061.54 nM PubChem BioAssay data set
NPT394 Cell line EKVX Homo sapiens GI50 n.a. 43651.58 nM PubChem BioAssay data set
NPT386 Cell line KM12 Homo sapiens GI50 n.a. 59292.53 nM PubChem BioAssay data set
NPT387 Cell line M14 Homo sapiens GI50 n.a. 72777.98 nM PubChem BioAssay data set
NPT398 Cell line UACC-62 Homo sapiens GI50 n.a. 33806.48 nM PubChem BioAssay data set
NPT323 Cell line SW-620 Homo sapiens GI50 n.a. 37844.26 nM PubChem BioAssay data set
NPT403 Cell line UACC-257 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT367 Cell line MDA-N Homo sapiens GI50 n.a. 47643.1 nM PubChem BioAssay data set
NPT379 Cell line HOP-62 Homo sapiens GI50 n.a. 25527.01 nM PubChem BioAssay data set
NPT383 Cell line SNB-19 Homo sapiens GI50 n.a. 35563.13 nM PubChem BioAssay data set
NPT384 Cell line TK-10 Homo sapiens GI50 n.a. 59292.53 nM PubChem BioAssay data set
NPT374 Cell line SF-539 Homo sapiens GI50 n.a. 23442.29 nM PubChem BioAssay data set
NPT376 Cell line A498 Homo sapiens GI50 n.a. 34040.82 nM PubChem BioAssay data set
NPT111 Cell line K562 Homo sapiens GI50 n.a. 29991.63 nM PubChem BioAssay data set
NPT457 Cell line BT-549 Homo sapiens GI50 n.a. 46451.53 nM PubChem BioAssay data set
NPT148 Cell line HCT-15 Homo sapiens GI50 n.a. 32359.37 nM PubChem BioAssay data set
NPT370 Cell line NCI-H23 Homo sapiens GI50 n.a. 52119.47 nM PubChem BioAssay data set
NPT407 Cell line COLO 205 Homo sapiens GI50 n.a. 68391.16 nM PubChem BioAssay data set
NPT146 Cell line SK-OV-3 Homo sapiens GI50 n.a. 41399.97 nM PubChem BioAssay data set
NPT395 Cell line SF-268 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT393 Cell line HCT-116 Homo sapiens GI50 n.a. 30199.52 nM PubChem BioAssay data set
NPT396 Cell line T47D Homo sapiens GI50 n.a. 25941.79 nM PubChem BioAssay data set
NPT382 Cell line OVCAR-5 Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT391 Cell line HCC 2998 Homo sapiens GI50 n.a. 46881.34 nM PubChem BioAssay data set
NPT385 Cell line SR Homo sapiens GI50 n.a. 12971.79 nM PubChem BioAssay data set
NPT397 Cell line NCI-H460 Homo sapiens GI50 n.a. 25468.3 nM PubChem BioAssay data set
NPT116 Cell line HL-60 Homo sapiens GI50 n.a. 23496.33 nM PubChem BioAssay data set
NPT308 Cell line CAKI-1 Homo sapiens GI50 n.a. 25703.96 nM PubChem BioAssay data set
NPT456 Cell line OVCAR-4 Homo sapiens GI50 n.a. 24660.39 nM PubChem BioAssay data set
NPT458 Cell line IGROV-1 Homo sapiens GI50 n.a. 32885.16 nM PubChem BioAssay data set
NPT381 Cell line OVCAR-8 Homo sapiens GI50 n.a. 37411.06 nM PubChem BioAssay data set
NPT112 Cell line MOLT-4 Homo sapiens GI50 n.a. 25585.86 nM PubChem BioAssay data set
NPT406 Cell line RXF 393 Homo sapiens GI50 n.a. 5847.9 nM PubChem BioAssay data set
NPT455 Cell line NCI-H522 Homo sapiens GI50 n.a. 16595.87 nM PubChem BioAssay data set
NPT404 Cell line CCRF-CEM Homo sapiens GI50 n.a. 25822.6 nM PubChem BioAssay data set
NPT401 Cell line 786-0 Homo sapiens GI50 n.a. 56885.29 nM PubChem BioAssay data set
NPT90 Cell line DU-145 Homo sapiens GI50 n.a. 47973.34 nM PubChem BioAssay data set
NPT375 Cell line Malme-3M Homo sapiens GI50 n.a. 67142.89 nM PubChem BioAssay data set
NPT389 Cell line RPMI-8226 Homo sapiens GI50 n.a. 22803.42 nM PubChem BioAssay data set
NPT380 Cell line U-251 Homo sapiens GI50 n.a. 43853.07 nM PubChem BioAssay data set
NPT170 Cell line SK-MEL-28 Homo sapiens GI50 n.a. 71944.9 nM PubChem BioAssay data set
NPT28833 No target No relevant target n.a. IC50 = 47400.0 nM PMID[29089261]
NPT28833 No target No relevant target n.a. EC50 = 22.4 nM PMID[29089261]

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 NPC604422 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
0.7925 Intermediate Similarity NPC266597
0.75 Intermediate Similarity NPC115323
0.75 Intermediate Similarity NPC607642
0.6897 Remote Similarity NPC12200
0.6786 Remote Similarity NPC77955
0.6786 Remote Similarity NPC113089
0.6604 Remote Similarity NPC172262
0.6481 Remote Similarity NPC57601
0.6441 Remote Similarity NPC255350
0.6429 Remote Similarity NPC333230
0.6364 Remote Similarity NPC70136
0.6167 Remote Similarity NPC69394
0.6102 Remote Similarity NPC281207
0.6094 Remote Similarity NPC269906
0.6071 Remote Similarity NPC603556
0.6066 Remote Similarity NPC12377
0.6066 Remote Similarity NPC256612
0.6066 Remote Similarity NPC283600
0.6066 Remote Similarity NPC195202
0.5902 Remote Similarity NPC55205
0.5833 Remote Similarity NPC250266
0.5763 Remote Similarity NPC23955
0.5738 Remote Similarity NPC163780
0.5738 Remote Similarity NPC312924
0.5667 Remote Similarity NPC205522
0.5667 Remote Similarity NPC215932
0.5645 Remote Similarity NPC183597
0.5574 Remote Similarity NPC70853
0.5574 Remote Similarity NPC604085
0.5556 Remote Similarity NPC2476
0.5556 Remote Similarity NPC602125
0.5538 Remote Similarity NPC605634
0.55 Remote Similarity NPC136840
0.541 Remote Similarity NPC110639
0.5397 Remote Similarity NPC50728
0.5397 Remote Similarity NPC159103
0.5397 Remote Similarity NPC20830
0.5397 Remote Similarity NPC602344
0.5373 Remote Similarity NPC261227
0.5362 Remote Similarity NPC213622
0.5362 Remote Similarity NPC183
0.5323 Remote Similarity NPC231772
0.5323 Remote Similarity NPC260895
0.5323 Remote Similarity NPC62536
0.5312 Remote Similarity NPC603596
0.5254 Remote Similarity NPC604293
0.5246 Remote Similarity NPC85233
0.5231 Remote Similarity NPC183950
0.5167 Remote Similarity NPC2771
0.5167 Remote Similarity NPC603094
0.5161 Remote Similarity NPC483774
0.5161 Remote Similarity NPC47815
0.5161 Remote Similarity NPC608264
0.5152 Remote Similarity NPC287275
0.5077 Remote Similarity NPC262623
0.5077 Remote Similarity NPC308451
0.5077 Remote Similarity NPC287101
0.5077 Remote Similarity NPC52005
0.5077 Remote Similarity NPC606638
0.5075 Remote Similarity NPC485299

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC604422 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
0.6441 Remote Similarity NPD2801 Pre-clinical

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