Natural Product: NPC602344

Natural Product IDNPC602344
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 KSAJVJYHNOORPX-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL77198
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 KSAJVJYHNOORPX-UHFFFAOYSA-N
Standard InCHI InChI=1S/C18H16O6/c1-21-11-5-6-12-14(9-11)24-18(17(20)16(12)19)10-4-7-13(22-2)15(8-10)23-3/h4-9,20H,1-3H3
SMILES COc1ccc2c(=O)c(O)c(-c3ccc(OC)c(OC)c3)oc2c1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   328.09 Volume:   325.865
?
Van der Waals volume.
Dense:   1.007 LogP:   2.204
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.446
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.047
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   18.0
TPSA:   78.13
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   1.0 Rings:   3.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.792 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.067 Fsp3:   0.167
MCE-18:   18.0
?
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:   1 PAINS Alert:   0
Colloidal aggregators:   0.301 Fluc inhibitor:   0.98
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.931
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.696
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.381 Promiscuous compounds:   0.674

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.08 MDCK Permeability:   -4.701
Pgp-inhibitor:   0.995 Pgp-substrate:   0.012
PAMPA:   0.014
?
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):   0.732
20% Bioavailability (F20%):   0.02 30% Bioavailability (F30%):   0.315
50% Bioavailability (F50%):   0.914

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.453
Plasma Protein Binding (PPB):   94.371% Volume Distribution (VD):   -0.467
Fu: 4.983%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.997
BSEP inhibitor:   0.998

ADMET: Metabolism

CYP1A2-inhibitor:   0.997 CYP1A2-substrate:   0.704
CYP2C19-inhibitor:   0.324 CYP2C19-substrate:   0.837
CYP2C9-inhibitor:   0.753 CYP2C9-substrate:   0.006
CYP2D6-inhibitor:   0.991 CYP2D6-substrate:   0.902
CYP3A4-inhibitor:   0.065 CYP3A4-substrate:   0.002
CYP2B6-substrate:   0.002 CYP2C8-inhibitor:   0.984
HLM stability:   0.972
?
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):  7.747 Half-life (T1/2):  1.427

ADMET: Toxicity

hERG Blockers:  0.148 hERG Blockers (10um):  0.461
Human Hepatotoxicity (H-HT):  0.439 Drug-induced Liver Injury (DILI):  0.857
AMES Toxicity:  0.591 Rat Oral Acute Toxicity:  0.382
Maximum Recommended Daily Dose:  0.463 Skin Sensitization:  0.31
Carcinogencity:  0.842 Eye Corrosion:  0.757
Eye Irritation:  0.985 Respiratory Toxicity:  0.727
Drug-induced Neurotoxicity:  0.318 Ototoxicity:  0.154
Hematotoxicity:  0.349 Drug-induced Nephrotoxicity:  0.2
Genotoxicity:  0.339 RPMI-8226 Immunitoxicity:  0.081
A549 Cytotoxicity:  0.109 Hek293 Cytotoxicity:  0.296
BCF:   1.049
?
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:   3.826
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.582
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.204
?
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
NPO48642 Umtiza listerana Genus Fabaceae 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
NPT208 Individual protein Cytochrome P450 1A2 Homo sapiens Inhibition n.a. n.a. % PMID[27411733]
NPT1422 Individual protein ATP-binding cassette sub-family G member 2 Homo sapiens IC50 = 1010.0 nM PMID[23851114]
NPT1422 Individual protein ATP-binding cassette sub-family G member 2 Homo sapiens IC50 = 1770.0 nM PMID[23851114]
NPT30108 Protein complex group Tubulin Homo sapiens IC50 > 40000.0 nM PMID[9632366]
NPT30108 Protein complex group Tubulin Homo sapiens Inhibition = 0.0 % PMID[9632366]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT137 Cell line L1210 Mus musculus Activity n.a. n.a. n.a. PMID[469554]
NPT407 Cell line COLO 205 Homo sapiens GI50 n.a. 28906.8 nM PubChem BioAssay data set
NPT306 Cell line PC-3 Homo sapiens GI50 n.a. 9375.62 nM PubChem BioAssay data set
NPT170 Cell line SK-MEL-28 Homo sapiens GI50 n.a. 8531.0 nM PubChem BioAssay data set
NPT306 Cell line PC-3 Homo sapiens IC50 = 19900.0 nM PMID[30165345]
NPT306 Cell line PC-3 Homo sapiens Activity = 79.0 % PMID[30165345]
NPT308 Cell line CAKI-1 Homo sapiens GI50 n.a. 3435.58 nM PubChem BioAssay data set
NPT306 Cell line PC-3 Homo sapiens Activity n.a. n.a. n.a. PMID[30165345]
NPT369 Cell line ACHN Homo sapiens GI50 n.a. 3539.97 nM PubChem BioAssay data set
NPT139 Cell line HT-29 Homo sapiens GI50 n.a. 4920.4 nM PubChem BioAssay data set
NPT383 Cell line SNB-19 Homo sapiens GI50 n.a. 15848.93 nM PubChem BioAssay data set
NPT112 Cell line MOLT-4 Homo sapiens GI50 n.a. 3221.07 nM PubChem BioAssay data set
NPT381 Cell line OVCAR-8 Homo sapiens GI50 n.a. 3706.81 nM PubChem BioAssay data set
NPT382 Cell line OVCAR-5 Homo sapiens GI50 n.a. 20844.91 nM PubChem BioAssay data set
NPT146 Cell line SK-OV-3 Homo sapiens GI50 n.a. 5420.01 nM PubChem BioAssay data set
NPT400 Cell line MDA-MB-435 Homo sapiens GI50 n.a. 4508.17 nM PubChem BioAssay data set
NPT393 Cell line HCT-116 Homo sapiens GI50 n.a. 4965.92 nM PubChem BioAssay data set
NPT306 Cell line PC-3 Homo sapiens Activity = 37.0 % PMID[30165345]
NPT375 Cell line Malme-3M Homo sapiens GI50 n.a. 15066.07 nM PubChem BioAssay data set
NPT389 Cell line RPMI-8226 Homo sapiens GI50 n.a. 4092.61 nM PubChem BioAssay data set
NPT306 Cell line PC-3 Homo sapiens Activity = 90.0 % PMID[30165345]
NPT116 Cell line HL-60 Homo sapiens GI50 n.a. 1659.59 nM PubChem BioAssay data set
NPT1374 Cell line WI-38 Homo sapiens Activity n.a. n.a. n.a. PMID[27411733]
NPT82 Cell line MDA-MB-231 Homo sapiens GI50 n.a. 4797.33 nM PubChem BioAssay data set
NPT81 Cell line A549 Homo sapiens Activity n.a. n.a. n.a. PMID[27411733]
NPT90 Cell line DU-145 Homo sapiens IC50 = 24900.0 nM PMID[30165345]
NPT384 Cell line TK-10 Homo sapiens GI50 n.a. 4909.08 nM PubChem BioAssay data set
NPT113 Cell line RAW264.7 Mus musculus Activity = 82.0 % PMID[25027933]
NPT380 Cell line U-251 Homo sapiens GI50 n.a. 3523.71 nM PubChem BioAssay data set
NPT395 Cell line SF-268 Homo sapiens GI50 n.a. 4841.72 nM PubChem BioAssay data set
NPT378 Cell line NCI/ADR-RES Homo sapiens GI50 n.a. 2233.57 nM PubChem BioAssay data set
NPT385 Cell line SR Homo sapiens GI50 n.a. 4083.19 nM PubChem BioAssay data set
NPT111 Cell line K562 Homo sapiens GI50 n.a. 4528.98 nM PubChem BioAssay data set
NPT616 Cell line MDCK Canis lupus familiaris Activity n.a. n.a. n.a. PMID[23851114]
NPT456 Cell line OVCAR-4 Homo sapiens GI50 n.a. 190.99 nM PubChem BioAssay data set
NPT401 Cell line 786-0 Homo sapiens Activity n.a. n.a. n.a. PMID[27411733]
NPT113 Cell line RAW264.7 Mus musculus Inhibition = 80.0 % PMID[25027933]
NPT306 Cell line PC-3 Homo sapiens Activity = 2.0 % PMID[30165345]
NPT394 Cell line EKVX Homo sapiens GI50 n.a. 6950.24 nM PubChem BioAssay data set
NPT404 Cell line CCRF-CEM Homo sapiens GI50 n.a. 2355.05 nM PubChem BioAssay data set
NPT2257 Cell line MCF-10A Homo sapiens IC50 = 23950.0 nM PMID[30165345]
NPT387 Cell line M14 Homo sapiens GI50 n.a. 5445.03 nM PubChem BioAssay data set
NPT388 Cell line NCI-H322M Homo sapiens GI50 n.a. 6109.42 nM PubChem BioAssay data set
NPT858 Cell line LNCaP Homo sapiens IC50 = 24500.0 nM PMID[30165345]
NPT379 Cell line HOP-62 Homo sapiens GI50 n.a. 3981.07 nM PubChem BioAssay data set
NPT376 Cell line A498 Homo sapiens GI50 n.a. 4965.92 nM PubChem BioAssay data set
NPT390 Cell line LOX IMVI Homo sapiens GI50 n.a. 5584.7 nM PubChem BioAssay data set
NPT372 Cell line HOP-92 Homo sapiens GI50 n.a. 4178.3 nM PubChem BioAssay data set
NPT367 Cell line MDA-N Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT377 Cell line OVCAR-3 Homo sapiens GI50 n.a. 2844.46 nM PubChem BioAssay data set
NPT391 Cell line HCC 2998 Homo sapiens GI50 n.a. 27861.21 nM PubChem BioAssay data set
NPT517 Cell line Panel NCI-60 (60 carcinoma cell lines) Homo sapiens GI50 = 5500.0 nM PMID[9632366]
NPT399 Cell line SF-295 Homo sapiens GI50 n.a. 10115.79 nM PubChem BioAssay data set
NPT458 Cell line IGROV-1 Homo sapiens GI50 n.a. 7447.32 nM PubChem BioAssay data set
NPT81 Cell line A549 Homo sapiens GI50 n.a. 4920.4 nM PubChem BioAssay data set
NPT148 Cell line HCT-15 Homo sapiens GI50 n.a. 3499.45 nM PubChem BioAssay data set
NPT455 Cell line NCI-H522 Homo sapiens GI50 n.a. 3133.29 nM PubChem BioAssay data set
NPT83 Cell line MCF7 Homo sapiens GI50 n.a. 3741.11 nM PubChem BioAssay data set
NPT397 Cell line NCI-H460 Homo sapiens GI50 n.a. 3349.65 nM PubChem BioAssay data set
NPT398 Cell line UACC-62 Homo sapiens GI50 n.a. 3228.49 nM PubChem BioAssay data set
NPT396 Cell line T47D Homo sapiens GI50 n.a. 100000.0 nM PubChem BioAssay data set
NPT323 Cell line SW-620 Homo sapiens GI50 n.a. 4965.92 nM PubChem BioAssay data set
NPT373 Cell line SK-MEL-5 Homo sapiens GI50 n.a. 5495.41 nM PubChem BioAssay data set
NPT371 Cell line UO-31 Homo sapiens GI50 n.a. 2466.04 nM PubChem BioAssay data set
NPT90 Cell line DU-145 Homo sapiens GI50 n.a. 4036.45 nM PubChem BioAssay data set
NPT403 Cell line UACC-257 Homo sapiens GI50 n.a. 6760.83 nM PubChem BioAssay data set
NPT28438 Unchecked Unchecked n.a. Ratio CC50/EC50 = 8.0 n.a. PMID[28064141]
NPT28438 Unchecked Unchecked n.a. Ratio CC50/EC50 = 8.0 n.a. PMID[27411733]
NPT21739 Cell line PWR-1E Homo sapiens IC50 > 50000.0 nM PMID[30165345]
NPT471 Organism Trypanosoma brucei brucei Trypanosoma brucei brucei Activity n.a. n.a. n.a. PMID[27411733]
NPT471 Organism Trypanosoma brucei brucei Trypanosoma brucei brucei EC50 = 2990.0 nM PMID[28064141]
NPT471 Organism Trypanosoma brucei brucei Trypanosoma brucei brucei EC50 = 2990.0 nM PMID[27411733]

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 NPC602344 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
0.7593 Intermediate Similarity NPC269652
0.7143 Intermediate Similarity NPC166753
0.7018 Intermediate Similarity NPC261548
0.6724 Remote Similarity NPC608664
0.6607 Remote Similarity NPC113089
0.6607 Remote Similarity NPC299923
0.6271 Remote Similarity NPC50728
0.6271 Remote Similarity NPC159103
0.6207 Remote Similarity NPC281207
0.6207 Remote Similarity NPC605146
0.5902 Remote Similarity NPC224137
0.5833 Remote Similarity NPC49824
0.5833 Remote Similarity NPC134677
0.5738 Remote Similarity NPC55205
0.5667 Remote Similarity NPC276905
0.5645 Remote Similarity NPC236769
0.5645 Remote Similarity NPC195202
0.5645 Remote Similarity NPC602125
0.5556 Remote Similarity NPC279930
0.5484 Remote Similarity NPC200740
0.541 Remote Similarity NPC250266
0.5397 Remote Similarity NPC93376
0.5397 Remote Similarity NPC308451
0.5397 Remote Similarity NPC604422
0.5345 Remote Similarity NPC604293
0.5312 Remote Similarity NPC252933
0.5246 Remote Similarity NPC44079
0.5246 Remote Similarity NPC185607
0.5246 Remote Similarity NPC152042
0.5238 Remote Similarity NPC176300
0.5238 Remote Similarity NPC69394
0.5231 Remote Similarity NPC227192
0.5167 Remote Similarity NPC333230
0.5161 Remote Similarity NPC87125
0.5161 Remote Similarity NPC241838
0.5161 Remote Similarity NPC143799
0.5156 Remote Similarity NPC75215

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC602344 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