NPASS Compound

Natural Product: NPC192678

Natural Product ID	NPC192678
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	KTEXNACQROZXEV-LLGHTPABSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	124833173
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001283] Terpene lactones [CHEMONTID:0001543] Sesquiterpene lactones [CHEMONTID:0001771] Germacranolides and derivatives

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 38 40 0 0 0 0 0 0 0 0999 V2000 -2.1788 -2.7356 -0.9944 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3963 -1.8165 -0.0034 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1145 -0.8234 0.4275 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7004 0.2124 1.3672 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7578 1.6269 0.9021 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9703 2.0424 -0.2613 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.6186 3.2813 -0.9654 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3919 1.9541 -0.3671 C 0 0 1 0 0 0 0 0 0 0 0 0 1.2691 1.1144 0.5403 C 0 0 1 0 0 0 0 0 0 0 0 0 1.4721 -0.2439 0.0075 C 0 0 2 0 0 0 0 0 0 0 0 0 1.0350 -1.4274 0.8112 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0323 -2.2005 0.1583 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9502 -0.4027 -0.2458 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5620 -1.5106 -0.6294 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5227 0.9013 0.0178 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7278 1.1811 -0.2609 O 0 0 0 0 0 0 0 0 0 0 0 0 2.5898 1.7132 0.5815 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.4405 1.1980 -1.2076 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.9345 -2.1627 -1.5230 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4494 -3.1550 -1.7090 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6688 -3.5181 -0.3984 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1679 -0.7434 0.0428 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5765 0.1281 2.1861 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8728 -0.0457 2.0407 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5285 2.3500 1.7432 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8720 1.8369 0.7599 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6346 3.0341 -1.2713 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5974 4.1286 -0.2522 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9750 3.5655 -1.8218 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9864 2.6798 -0.9871 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9704 1.1255 1.5933 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0379 -0.2903 -1.0373 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9376 -2.1788 0.8816 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9469 -1.1611 1.8636 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3783 -2.3763 -0.9210 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0377 -3.2923 0.5283 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6314 -1.5487 -0.7921 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0396 -2.4406 -0.8049 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 0 3 4 1 0 4 5 1 0 5 6 1 0 6 7 1 6 6 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 1 0 10 13 1 0 13 14 2 0 13 15 1 0 15 16 2 0 15 17 1 0 8 18 1 0 12 2 1 0 18 6 1 0 17 9 1 0 1 19 1 0 1 20 1 0 1 21 1 0 3 22 1 0 4 23 1 0 4 24 1 0 5 25 1 0 5 26 1 0 7 27 1 0 7 28 1 0 7 29 1 0 8 30 1 6 9 31 1 1 10 32 1 6 11 33 1 0 11 34 1 0 12 35 1 0 12 36 1 0 14 37 1 0 14 38 1 0 M END

Standard InCHIKey	KTEXNACQROZXEV-LLGHTPABSA-N
Standard InCHI	InChI=1S/C15H20O3/c1-9-5-4-8-15(3)13(18-15)12-11(7-6-9)10(2)14(16)17-12/h5,11-13H,2,4,6-8H2,1,3H3/b9-5-/t11-,12-,13-,15+/m1/s1
SMILES	C/C/1=C/CC[C@@]2(C)[C@@H]([C@H]3[C@H](CC1)C(=C)C(=O)O3)O2

Calculated Properties

Physi-Chem Properties

Molecular Weight:	248.14	Volume:	260.788 ? Van der Waals volume.
Dense:	0.952	LogP:	2.881 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.054 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.964 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	0.0	Rigid Bonds:	18.0
TPSA:	38.83 ? Topological Polar Surface Area.	H-Bond Acceptor:	3.0
H-Bond Donor:	0.0	Rings:	3.0
Heavy Atoms:	3.0

MedChem Properties

QED Drug-Likeness Score:	0.286	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.723	Fsp³:	0.667
MCE-18:	47.52 ? 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:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.291	Fluc inhibitor:	0.273 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.009 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.085 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.786	Promiscuous compounds:	0.237

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.574	MDCK Permeability:	-4.726
Pgp-inhibitor:	0.414	Pgp-substrate:	0.064
PAMPA:	0.197 ? 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):	0.029
20% Bioavailability (F20%):	0.435	30% Bioavailability (F30%):	0.68
50% Bioavailability (F50%):	0.889

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.209	MRP1:	0.964
Plasma Protein Binding (PPB):	97.79%	Volume Distribution (VD):	0.484
Fu:	2.458% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.913
OATP1B3 inhibitor:	0.934	BCRP inhibitor:	0.018
BSEP inhibitor:	0.952

ADMET: Metabolism

CYP1A2-inhibitor:	0.064	CYP1A2-substrate:	0.563
CYP2C19-inhibitor:	0.465	CYP2C19-substrate:	0.383
CYP2C9-inhibitor:	0.486	CYP2C9-substrate:	0.006
CYP2D6-inhibitor:	0.112	CYP2D6-substrate:	0.067
CYP3A4-inhibitor:	0.49	CYP3A4-substrate:	0.894
CYP2B6-substrate:	0.019	CYP2C8-inhibitor:	0.797
HLM stability:	0.878 ? 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):

8.986

Half-life (T1/2):

2.118

ADMET: Toxicity

hERG Blockers:	0.018	hERG Blockers (10um):	0.249
Human Hepatotoxicity (H-HT):	0.764	Drug-induced Liver Injury (DILI):	0.788
AMES Toxicity:	0.593	Rat Oral Acute Toxicity:	0.472
Maximum Recommended Daily Dose:	0.694	Skin Sensitization:	0.999
Carcinogencity:	0.744	Eye Corrosion:	0.833
Eye Irritation:	0.964	Respiratory Toxicity:	0.185
Drug-induced Neurotoxicity:	0.418	Ototoxicity:	0.234
Hematotoxicity:	0.646	Drug-induced Nephrotoxicity:	0.685
Genotoxicity:	0.68	RPMI-8226 Immunitoxicity:	0.182
A549 Cytotoxicity:	0.268	Hek293 Cytotoxicity:	0.507
BCF:	2.032 ? 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:	4.43 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.737 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.382 ? 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
NPO13745	Gynoxys verrucosa	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[27057812]
NPO13745	Gynoxys verrucosa	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO13745	Gynoxys verrucosa	Species	Asteraceae	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 NPC192678 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	22085
0.1-0.2	24364
0.2-0.3	2954
0.3-0.4	351
0.4-0.5	60
0.5-0.6	27
0.6-0.7	8
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	5

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC38468
1.0	High Similarity	NPC319795
1.0	High Similarity	NPC50362
1.0	High Similarity	NPC488056
1.0	High Similarity	NPC605079
0.7708	Intermediate Similarity	NPC608845
0.6939	Remote Similarity	NPC49342
0.6939	Remote Similarity	NPC251385
0.6346	Remote Similarity	NPC303942
0.6346	Remote Similarity	NPC57405
0.6327	Remote Similarity	NPC207188
0.6296	Remote Similarity	NPC605339
0.6154	Remote Similarity	NPC151770
0.6	Remote Similarity	NPC471147
0.5965	Remote Similarity	NPC482125
0.5965	Remote Similarity	NPC482124
0.5926	Remote Similarity	NPC484396
0.5789	Remote Similarity	NPC475659
0.569	Remote Similarity	NPC487572
0.569	Remote Similarity	NPC473859
0.5517	Remote Similarity	NPC231889
0.551	Remote Similarity	NPC58956
0.551	Remote Similarity	NPC163003
0.551	Remote Similarity	NPC295633
0.551	Remote Similarity	NPC269206
0.5424	Remote Similarity	NPC483718
0.5357	Remote Similarity	NPC272814
0.5263	Remote Similarity	NPC481994
0.5254	Remote Similarity	NPC329857
0.5254	Remote Similarity	NPC469718
0.5246	Remote Similarity	NPC288876
0.5185	Remote Similarity	NPC256273
0.5179	Remote Similarity	NPC70251
0.5179	Remote Similarity	NPC475881
0.5172	Remote Similarity	NPC481908
0.5172	Remote Similarity	NPC481801
0.5172	Remote Similarity	NPC481993
0.5167	Remote Similarity	NPC474035
0.5167	Remote Similarity	NPC215988
0.5167	Remote Similarity	NPC81386
0.5094	Remote Similarity	NPC93213

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC192678 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	7267
0.1-0.2	1829
0.2-0.3	51
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	1

Similarity Score	Similarity Level	Drug ID	Developmental Stage
1.0	High Similarity	NPD1733	Clinical (unspecified phase)

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