NPASS Compound

Natural Product: NPC104688

Natural Product ID	NPC104688
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	RTNPCOBSXBGDMO-ARJAWSKDSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	5362720
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0004603] Organic oxygen compounds [CHEMONTID:0000323] Organooxygen compounds [CHEMONTID:0001831] Carbonyl compounds [CHEMONTID:0000124] Aldehydes [CHEMONTID:0002229] Medium-chain aldehydes

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 26 25 0 0 0 0 0 0 0 0999 V2000 4.1361 0.0027 0.0457 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7728 0.6697 0.2700 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9286 -0.2365 1.0487 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7662 -0.7546 0.6763 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1673 -0.4529 -0.6437 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2026 0.2267 -0.5132 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1043 -0.7099 0.2241 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4989 -0.1487 0.4102 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4489 1.1335 1.1912 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4573 1.7598 1.4594 O 0 0 0 0 0 0 0 0 0 0 0 0 4.8041 0.1812 0.8981 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5759 0.3312 -0.9303 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9251 -1.0967 -0.0903 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3626 1.1026 -0.6303 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0227 1.5634 0.9285 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2985 -0.5190 2.0538 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2642 -1.4159 1.3734 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8147 0.1184 -1.3192 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0245 -1.4426 -1.1878 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0959 1.1701 0.0665 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5716 0.5144 -1.5038 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6887 -0.9775 1.1955 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1853 -1.6397 -0.3738 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0488 -0.0423 -0.5206 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0525 -0.8734 1.0506 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5087 1.5361 1.5380 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 2 0 4 5 1 0 5 6 1 0 6 7 1 0 7 8 1 0 8 9 1 0 9 10 2 0 1 11 1 0 1 12 1 0 1 13 1 0 2 14 1 0 2 15 1 0 3 16 1 0 4 17 1 0 5 18 1 0 5 19 1 0 6 20 1 0 6 21 1 0 7 22 1 0 7 23 1 0 8 24 1 0 8 25 1 0 9 26 1 0 M END

Standard InCHIKey	RTNPCOBSXBGDMO-ARJAWSKDSA-N
Standard InCHI	InChI=1S/C9H16O/c1-2-3-4-5-6-7-8-9-10/h3-4,9H,2,5-8H2,1H3/b4-3-
SMILES	CC/C=CCCCCC=O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	140.12	Volume:	167.738 ? Van der Waals volume.
Dense:	0.835	LogP:	2.766 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.429 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.539 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	6.0	Rigid Bonds:	2.0
TPSA:	17.07 ? Topological Polar Surface Area.	H-Bond Acceptor:	1.0
H-Bond Donor:	0.0	Rings:	0.0
Heavy Atoms:	1.0

MedChem Properties

QED Drug-Likeness Score:	0.315	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.58	Fsp³:	0.667
MCE-18:	0.0 ? 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:	Accepted	BMS Rule:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.014	Fluc inhibitor:	0.001 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.001 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.018 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	1.0	Promiscuous compounds:	0.34

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.621	MDCK Permeability:	-4.632
Pgp-inhibitor:	0.925	Pgp-substrate:	0.004
PAMPA:	0.003 ? 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):	0.108
20% Bioavailability (F20%):	0.234	30% Bioavailability (F30%):	0.375
50% Bioavailability (F50%):	0.361

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.727	MRP1:	0.839
Plasma Protein Binding (PPB):	96.889%	Volume Distribution (VD):	-0.649
Fu:	3.276% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.008
OATP1B3 inhibitor:	0.369	BCRP inhibitor:	0.69
BSEP inhibitor:	0.992

ADMET: Metabolism

CYP1A2-inhibitor:	0.103	CYP1A2-substrate:	0.912
CYP2C19-inhibitor:	0.745	CYP2C19-substrate:	0.848
CYP2C9-inhibitor:	0.939	CYP2C9-substrate:	0.004
CYP2D6-inhibitor:	0.263	CYP2D6-substrate:	0.946
CYP3A4-inhibitor:	0.009	CYP3A4-substrate:	0.775
CYP2B6-substrate:	0.075	CYP2C8-inhibitor:	0.998
HLM stability:	0.455 ? 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):

7.898

Half-life (T1/2):

0.669

ADMET: Toxicity

hERG Blockers:	0.18	hERG Blockers (10um):	0.444
Human Hepatotoxicity (H-HT):	0.153	Drug-induced Liver Injury (DILI):	0.013
AMES Toxicity:	0.292	Rat Oral Acute Toxicity:	0.117
Maximum Recommended Daily Dose:	0.017	Skin Sensitization:	1.0
Carcinogencity:	0.028	Eye Corrosion:	1.0
Eye Irritation:	0.999	Respiratory Toxicity:	0.842
Drug-induced Neurotoxicity:	0.114	Ototoxicity:	0.125
Hematotoxicity:	0.029	Drug-induced Nephrotoxicity:	0.55
Genotoxicity:	0.001	RPMI-8226 Immunitoxicity:	0.026
A549 Cytotoxicity:	0.056	Hek293 Cytotoxicity:	0.031
BCF:	0.914 ? 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:	3.488 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.613 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.274 ? 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
NPO11277	Baeckea frutescens	Species	Myrtaceae	Eukaryota	n.a.	leaf	n.a.	DOI[10.1016/S0031-9422(98)00534-2]
NPO11277	Baeckea frutescens	Species	Myrtaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[12932146]
NPO11100	Artemisia capillaris	Species	Asteraceae	Eukaryota	n.a.	whole plant	n.a.	PMID[21428416]
NPO11100	Artemisia capillaris	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[22870812]
NPO11100	Artemisia capillaris	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[23435948]
NPO11100	Artemisia capillaris	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[25737008]
NPO11277	Baeckea frutescens	Species	Myrtaceae	Eukaryota	aerial parts	Nanning, Guangxi Province, China	2014-OCT	PMID[28753309]
NPO10942	Retama sphaerocarpa	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[38847466]
NPO44270	Retama dasycarpa	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[38847466]
NPO11277	Baeckea frutescens	Species	Myrtaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[39064968]
NPO10942	Retama sphaerocarpa	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO11277	Baeckea frutescens	Species	Myrtaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO31579	Artemisia capillaries	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO11100	Artemisia capillaris	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO11100	Artemisia capillaris	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO11100	Artemisia capillaris	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO11100	Artemisia capillaris	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO11277	Baeckea frutescens	Species	Myrtaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO31579	Artemisia capillaries	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO11100	Artemisia capillaris	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO11100	Artemisia capillaris	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO10942	Retama sphaerocarpa	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO11277	Baeckea frutescens	Species	Myrtaceae	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
NPO10942	Retama sphaerocarpa	Oil	n.a.	2.82	n.a.	n.a.	%	PMID[38847466]
NPO11277	Baeckea frutescens	Oil	n.a.	1.03	n.a.	n.a.	%	PMID[39064968]
NPO44270	Retama dasycarpa	Oil	n.a.	2.82	n.a.	n.a.	%	PMID[38847466]

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
-	Rattus norvegicus	LD50	>	5000.0	mg/kg	ToxVal
-	Rattus norvegicus	NOAEL	=	127.0	mg/kg-day	ToxVal
-	Mus musculus	LD50	>	5000.0	mg/kg	ToxVal
-	Cavia porcellus	LD50	>	5000.0	mg/kg	ToxVal

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 NPC104688 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	36015
0.1-0.2	12894
0.2-0.3	818
0.3-0.4	85
0.4-0.5	25
0.5-0.6	9
0.6-0.7	0
0.7-0.8	0
0.8-0.85	2
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8095	Intermediate Similarity	NPC11487
0.8095	Intermediate Similarity	NPC239754
0.7727	Intermediate Similarity	NPC44363
0.7727	Intermediate Similarity	NPC110234
0.7727	Intermediate Similarity	NPC163751
0.5652	Remote Similarity	NPC601585
0.5417	Remote Similarity	NPC33761
0.5238	Remote Similarity	NPC59581
0.5217	Remote Similarity	NPC279300
0.52	Remote Similarity	NPC67920
0.52	Remote Similarity	NPC33489
0.52	Remote Similarity	NPC298710
0.52	Remote Similarity	NPC311716
0.52	Remote Similarity	NPC287397

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC104688 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	7545
0.1-0.2	1556
0.2-0.3	33
0.3-0.4	15
0.4-0.5	1
0.5-0.6	0
0.6-0.7	0
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
		NPD

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