NPASS Compound

Natural Product: NPC260578

Natural Product ID	NPC260578
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	HTCXXOQBBXKJIN-UHFFFAOYSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	6430783
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0004603] Organic oxygen compounds [CHEMONTID:0000323] Organooxygen compounds [CHEMONTID:0001831] Carbonyl compounds [CHEMONTID:0000118] Ketones

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 27 28 0 0 0 0 0 0 0 0999 V2000 -1.9362 0.5971 -1.3411 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3950 0.1304 -0.0113 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5092 -0.0796 0.9577 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3513 1.1249 0.5302 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8554 0.6008 -0.1105 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1850 0.8557 0.4512 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9467 -0.3802 -0.0795 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8939 -1.3827 -0.3620 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9829 -2.3885 -0.9996 O 0 0 0 0 0 0 0 0 0 0 0 0 0.6967 -0.8843 0.3103 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6169 -1.1651 -0.2891 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9068 0.0882 -1.5230 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0012 1.6879 -1.4277 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2613 0.2318 -2.1655 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9629 -1.0718 0.9194 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1505 0.0901 2.0143 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2882 0.7078 0.7345 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2810 0.9852 1.6329 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6402 2.1557 0.2933 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7794 0.6383 -1.2077 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1427 0.8402 1.5464 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6271 1.7831 0.0459 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6056 -0.7984 0.7025 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5115 -0.0719 -0.9719 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7380 -0.9394 1.4142 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1307 -1.9757 0.2874 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5336 -1.3798 -1.3513 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 2 4 1 0 4 5 1 0 5 6 1 0 6 7 1 0 7 8 1 0 8 9 2 0 8 10 1 0 10 11 1 0 11 2 1 0 10 5 1 0 1 12 1 0 1 13 1 0 1 14 1 0 3 15 1 0 3 16 1 0 3 17 1 0 4 18 1 0 4 19 1 0 5 20 1 0 6 21 1 0 6 22 1 0 7 23 1 0 7 24 1 0 10 25 1 0 11 26 1 0 11 27 1 0 M END

Standard InCHIKey	HTCXXOQBBXKJIN-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C10H16O/c1-10(2)5-7-3-4-9(11)8(7)6-10/h7-8H,3-6H2,1-2H3
SMILES	CC1(C)CC2CCC(=O)C2C1

Calculated Properties

Physi-Chem Properties

Molecular Weight:	152.12	Volume:	170.557 ? Van der Waals volume.
Dense:	0.892	LogP:	2.64 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.513 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.197 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	0.0	Rigid Bonds:	10.0
TPSA:	17.07 ? Topological Polar Surface Area.	H-Bond Acceptor:	1.0
H-Bond Donor:	0.0	Rings:	2.0
Heavy Atoms:	1.0

MedChem Properties

QED Drug-Likeness Score:	0.521	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.556	Fsp³:	0.9
MCE-18:	32.842 ? 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:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.059	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.005 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.004 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.922	Promiscuous compounds:	0.014

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.685	MDCK Permeability:	-4.85
Pgp-inhibitor:	0.844	Pgp-substrate:	0.005
PAMPA:	0.133 ? 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):	0.079
20% Bioavailability (F20%):	0.019	30% Bioavailability (F30%):	0.073
50% Bioavailability (F50%):	0.399

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.556	MRP1:	0.714
Plasma Protein Binding (PPB):	71.881%	Volume Distribution (VD):	-0.054
Fu:	28.26% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.696
OATP1B3 inhibitor:	0.944	BCRP inhibitor:	0.054
BSEP inhibitor:	0.936

ADMET: Metabolism

CYP1A2-inhibitor:	0.006	CYP1A2-substrate:	0.323
CYP2C19-inhibitor:	0.983	CYP2C19-substrate:	0.151
CYP2C9-inhibitor:	0.756	CYP2C9-substrate:	0.008
CYP2D6-inhibitor:	0.573	CYP2D6-substrate:	0.005
CYP3A4-inhibitor:	0.002	CYP3A4-substrate:	0.001
CYP2B6-substrate:	0.812	CYP2C8-inhibitor:	0.018
HLM stability:	0.853 ? 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):

9.913

Half-life (T1/2):

1.095

ADMET: Toxicity

hERG Blockers:	0.083	hERG Blockers (10um):	0.443
Human Hepatotoxicity (H-HT):	0.592	Drug-induced Liver Injury (DILI):	0.301
AMES Toxicity:	0.488	Rat Oral Acute Toxicity:	0.337
Maximum Recommended Daily Dose:	0.43	Skin Sensitization:	0.407
Carcinogencity:	0.601	Eye Corrosion:	0.729
Eye Irritation:	0.965	Respiratory Toxicity:	0.542
Drug-induced Neurotoxicity:	0.668	Ototoxicity:	0.364
Hematotoxicity:	0.422	Drug-induced Nephrotoxicity:	0.264
Genotoxicity:	0.137	RPMI-8226 Immunitoxicity:	0.052
A549 Cytotoxicity:	0.078	Hek293 Cytotoxicity:	0.193
BCF:	0.491 ? 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:	3.048 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.367 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.599 ? 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
NPO29141	Panax ginseng	Species	Araliaceae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.1016/j.jarmap.2018.11.004]
NPO29141	Panax ginseng	Species	Araliaceae	Eukaryota	n.a.	leaf	n.a.	PMID[18409045]
NPO29141	Panax ginseng	Species	Araliaceae	Eukaryota	flower buds	n.a.	n.a.	PMID[19926279]
NPO29141	Panax ginseng	Species	Araliaceae	Eukaryota	n.a.	root	n.a.	PMID[2092947]
NPO29141	Panax ginseng	Species	Araliaceae	Eukaryota	berry	n.a.	n.a.	PMID[21216145]
NPO29141	Panax ginseng	Species	Araliaceae	Eukaryota	leaves	n.a.	n.a.	PMID[24290061]
NPO29141	Panax ginseng	Species	Araliaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[24968750]
NPO29141	Panax ginseng	Species	Araliaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[25152999]
NPO29141	Panax ginseng	Species	Araliaceae	Eukaryota	stems-leaves	n.a.	n.a.	PMID[26420067]
NPO29141	Panax ginseng	Species	Araliaceae	Eukaryota	n.a.	stem	n.a.	PMID[27914541]
NPO29141	Panax ginseng	Species	Araliaceae	Eukaryota	Flower Buds	n.a.	n.a.	PMID[28345906]
NPO29141	Panax ginseng	Species	Araliaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[32129622]
NPO29141	Panax ginseng	Species	Araliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO29141	Panax ginseng	Species	Araliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO29141	Panax ginseng	Species	Araliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[MetaboLights]
NPO29141	Panax ginseng	Species	Araliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO29141	Panax ginseng	Species	Araliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO29141	Panax ginseng	Species	Araliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO29141	Panax ginseng	Species	Araliaceae	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

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 NPC260578 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	26941
0.1-0.2	22209
0.2-0.3	679
0.3-0.4	23
0.4-0.5	7
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	Natural Product ID
		NPC

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC260578 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6374
0.1-0.2	2666
0.2-0.3	108
0.3-0.4	2
0.4-0.5	0
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