NPASS Compound

Natural Product: NPC277335

Natural Product ID	NPC277335
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	QKNZNUNCDJZTCH-UHFFFAOYSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	16296
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0002448] Benzenoids [CHEMONTID:0002279] Benzene and substituted derivatives [CHEMONTID:0000176] Benzoic acids and derivatives [CHEMONTID:0001350] Benzoic acid esters

The Chemical Classification was calculated by Classyfire, a software for chemical taxonomy calculation. Reference: DOI:10.1186/s13321-016-0174-y.

Chemical Representations

RDKit 3D 30 30 0 0 0 0 0 0 0 0999 V2000 -4.4252 -0.3229 -0.8978 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0503 -0.6311 -1.3983 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0466 0.3778 -0.8626 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0732 0.2939 0.6625 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0905 1.2793 1.2536 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2262 1.0525 0.8496 O 0 0 0 0 0 0 0 0 0 0 0 0 0.9397 -0.0963 1.0699 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3790 -1.0378 1.6864 O 0 0 0 0 0 0 0 0 0 0 0 0 2.3313 -0.2400 0.6018 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9237 0.8077 -0.0722 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2213 0.7400 -0.5371 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9358 -0.4186 -0.3129 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3651 -1.4803 0.3589 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0599 -1.3713 0.8089 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7601 -1.1035 -0.1947 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5084 0.7032 -0.4691 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1345 -0.3466 -1.7538 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7660 -1.6658 -1.0873 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0179 -0.5945 -2.4897 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4425 1.3824 -1.1257 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0341 0.1860 -1.2160 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8906 -0.7315 1.0245 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0780 0.6091 0.9822 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3782 2.2947 0.8890 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2330 1.2934 2.3507 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3375 1.7017 -0.2320 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6997 1.5523 -1.0670 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9486 -0.4634 -0.6792 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9595 -2.3839 0.5195 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6017 -2.1998 1.3380 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 1 0 4 5 1 0 5 6 1 0 6 7 1 0 7 8 2 0 7 9 1 0 9 10 2 0 10 11 1 0 11 12 2 0 12 13 1 0 13 14 2 0 14 9 1 0 1 15 1 0 1 16 1 0 1 17 1 0 2 18 1 0 2 19 1 0 3 20 1 0 3 21 1 0 4 22 1 0 4 23 1 0 5 24 1 0 5 25 1 0 10 26 1 0 11 27 1 0 12 28 1 0 13 29 1 0 14 30 1 0 M END

Standard InCHIKey	QKNZNUNCDJZTCH-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C12H16O2/c1-2-3-7-10-14-12(13)11-8-5-4-6-9-11/h4-6,8-9H,2-3,7,10H2,1H3
SMILES	CCCCCOC(=O)c1ccccc1

Calculated Properties

Physi-Chem Properties

Molecular Weight:	192.12	Volume:	214.586 ? Van der Waals volume.
Dense:	0.895	LogP:	3.944 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.242 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.933 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	6.0	Rigid Bonds:	7.0
TPSA:	26.3 ? Topological Polar Surface Area.	H-Bond Acceptor:	2.0
H-Bond Donor:	0.0	Rings:	1.0
Heavy Atoms:	2.0

MedChem Properties

QED Drug-Likeness Score:	0.529	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	1.356	Fsp³:	0.417
MCE-18:	5.0 ? 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:	Rejected
Golden Triangle Rule:	Accepted	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.025	Fluc inhibitor:	0.301 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.01 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.131 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.986	Promiscuous compounds:	0.379

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.719	MDCK Permeability:	-4.548
Pgp-inhibitor:	0.348	Pgp-substrate:	0.043
PAMPA:	0.12 ? 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):	0.002
20% Bioavailability (F20%):	0.134	30% Bioavailability (F30%):	0.092
50% Bioavailability (F50%):	0.225

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.783	MRP1:	0.99
Plasma Protein Binding (PPB):	97.817%	Volume Distribution (VD):	0.221
Fu:	2.218% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.541
OATP1B3 inhibitor:	0.945	BCRP inhibitor:	0.144
BSEP inhibitor:	0.836

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	1.0
CYP2C19-inhibitor:	0.021	CYP2C19-substrate:	0.97
CYP2C9-inhibitor:	0.002	CYP2C9-substrate:	0.842
CYP2D6-inhibitor:	0.01	CYP2D6-substrate:	0.304
CYP3A4-inhibitor:	0.852	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.101	CYP2C8-inhibitor:	0.999
HLM stability:	1.0 ? 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):

6.273

Half-life (T1/2):

0.381

ADMET: Toxicity

hERG Blockers:	0.278	hERG Blockers (10um):	0.829
Human Hepatotoxicity (H-HT):	0.042	Drug-induced Liver Injury (DILI):	0.3
AMES Toxicity:	0.054	Rat Oral Acute Toxicity:	0.072
Maximum Recommended Daily Dose:	0.092	Skin Sensitization:	0.683
Carcinogencity:	0.602	Eye Corrosion:	0.477
Eye Irritation:	0.995	Respiratory Toxicity:	0.135
Drug-induced Neurotoxicity:	0.248	Ototoxicity:	0.067
Hematotoxicity:	0.009	Drug-induced Nephrotoxicity:	0.043
Genotoxicity:	0.001	RPMI-8226 Immunitoxicity:	0.046
A549 Cytotoxicity:	0.046	Hek293 Cytotoxicity:	0.281
BCF:	1.251 ? 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:	4.068 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.026 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.799 ? 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
NPO28146	Liriope spicata	Species	Asparagaceae	Eukaryota	Tuberous root	n.a.	n.a.	PMID[19874043]
NPO9773	Sideritis raeseri	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[37509192]
NPO57489	Acacia gerrardii	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[38299486]
NPO5275	Liriope muscari	Species	Asparagaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO57489	Acacia gerrardii	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO9773	Sideritis raeseri	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO28146	Liriope spicata	Species	Asparagaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO5275	Liriope muscari	Species	Asparagaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO28146	Liriope spicata	Species	Asparagaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO5275	Liriope muscari	Species	Asparagaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO28146	Liriope spicata	Species	Asparagaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO5275	Liriope muscari	Species	Asparagaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO28146	Liriope spicata	Species	Asparagaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO9773	Sideritis raeseri	Species	Lamiaceae	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
NPO57489	Acacia gerrardii	Oil	Leaves	0.51	n.a.	n.a.	%	PMID[38299486]
NPO9773	Sideritis raeseri	Oil	n.a.	0.12	n.a.	n.a.	%	PMID[37509192]

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

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

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 NPC277335 and all remaining natural products in the NPASS database.
● The right table: Most similar natural products (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	19525
0.1-0.2	27439
0.2-0.3	2638
0.3-0.4	193
0.4-0.5	34
0.5-0.6	14
0.6-0.7	8
0.7-0.8	0
0.8-0.85	0
0.85-0.9	1
0.9-0.95	1
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.9032	High Similarity	NPC78701
0.8667	High Similarity	NPC608938
0.7419	Intermediate Similarity	NPC92754
0.7273	Intermediate Similarity	NPC604461
0.697	Remote Similarity	NPC146351
0.6857	Remote Similarity	NPC93084
0.6857	Remote Similarity	NPC251854
0.6857	Remote Similarity	NPC601045
0.6452	Remote Similarity	NPC249912
0.6216	Remote Similarity	NPC35448
0.6176	Remote Similarity	NPC10251
0.6154	Remote Similarity	NPC607895
0.5897	Remote Similarity	NPC603245
0.5897	Remote Similarity	NPC604243
0.5882	Remote Similarity	NPC225060
0.5641	Remote Similarity	NPC270699
0.5476	Remote Similarity	NPC90522
0.5366	Remote Similarity	NPC156892
0.5333	Remote Similarity	NPC321852
0.5278	Remote Similarity	NPC486840
0.5135	Remote Similarity	NPC469574
0.5116	Remote Similarity	NPC604244
0.5111	Remote Similarity	NPC295406
0.5111	Remote Similarity	NPC200422
0.5111	Remote Similarity	NPC289572
0.5111	Remote Similarity	NPC157478

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC277335 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	2876
0.1-0.2	5573
0.2-0.3	655
0.3-0.4	35
0.4-0.5	9
0.5-0.6	1
0.6-0.7	1
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.6176	Remote Similarity	NPD2182	Pre-clinical
0.5789	Remote Similarity	NPD553	Phase 4

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